bmj.com Rapid Responses for Spurgeon, 326 (7381) 126

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NEWS EXTRA:
David Spurgeon
Canadian aboriginals in Vancouver face AIDS epidemic
BMJ 2003; 326: 126e [Full text]

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Rapid Responses published:

Aids and sex: Gareth Lloyd (17 January 2003)

Sex has nothing to do with AIDS: David Rasnick (20 January 2003)

Let us call a spade a spade: Richard G Fiddian-Green (21 January 2003)

Sex has plenty to do with AIDS, at least in sub-Saharan Africa: Colin D Butler (21 January 2003)

HIV-1 and HIV-2 are sexually transmitted lentiviruses: Brian T Foley (24 January 2003)

Correction Re: HIV-1 and HIV-2 are sexually transmitted lentiviruses: Brian T Foley (24 January 2003)

Canadian aboriginals in Vancouver face AIDS epidemic: James E Parker (25 January 2003)

Let�s scrutinize the evidence: David Rasnick (26 January 2003)

Re: Let�s scrutinize the evidence: Brian T Foley (28 January 2003)

Foley wants to scrutinize Padian et al. first: David Rasnick (29 January 2003)

Re: Foley wants to scrutinize Padian et al. first: Brian T Foley (30 January 2003)

Checking Rasnick's Citations showing HIV not transmitted sexually.: Brian T Foley (30 January 2003)

Still no sexual transmission of HIV, let alone AIDS: David Rasnick (31 January 2003)

Re: Still no sexual transmission of HIV, let alone AIDS: Brian T Foley (1 February 2003)

Potentially harmful letters should be peer reviewed: Riccardo Baschetti (1 February 2003)

Baschetti wants to end debate: David Rasnick (2 February 2003)

An AIDS Ignorance Epidemic?: Tony Floyd (2 February 2003)

Re: Baschetti wants to end debate: Riccardo Baschetti (3 February 2003)

Rasnick can debate till the cows come home: Brian T Foley (3 February 2003)

Sex Without Condoms and Russian Roulette: Tyrone Banks (3 February 2003)

Quacks Don't Care for Facts - AIDS Ignorance Epidemic: Tony Floyd (4 February 2003)

One more thing before we move on to the drugs: David Rasnick (4 February 2003)

Re: One more thing before we move on to the drugs: Brian T Foley (5 February 2003)

Eyewitness accounts: Brian T Foley (6 February 2003)

Foley's references, stay tuned: David Rasnick (6 February 2003)

HIV: a marker of barrier disruptions and personal hygiene?: Richard G Fiddian-Green (6 February 2003)

Re: Foley's references, stay tuned: Brian T Foley (7 February 2003)

Re: HIV: a marker of barrier disruptions and personal hygiene?: Brian T Foley (7 February 2003)

Wrong Question ?: James E Parker (7 February 2003)

Prelude to critique: David Rasnick (8 February 2003)

Evidence against sexual transmission of HIV and AIDS.: David Rasnick (9 February 2003)

Promised critique of Foley�s references: David Rasnick (9 February 2003)

Re: Foley and barrier integrity: Richard G Fiddian-Green (10 February 2003)

AIDS Denial May be an Excuse for Not Wearing Condoms: Tony Floyd (13 February 2003)

Apparently, debate and condoms are not compatible: David Rasnick (14 February 2003)

Re: Evidence against sexual transmission of HIV and AIDS.: Brian T Foley (15 February 2003)

Specious Arguments That HIV is Not Transmitted by Heterosexual Intercourse: Tony Floyd (15 February 2003)

HIV denial: Peter J Flegg (18 February 2003)

Re: Apparently, debate and condoms are not compatible: Martin Delaney (19 February 2003)

HIV antibody test is the Achilles heel of AIDS Inc.: David Rasnick (19 February 2003)

Re: Promised critique of Foley�s references: Brian T Foley (19 February 2003)

HIV is Not Good: Tony Floyd (19 February 2003)

A new rapid and accurate test for detecting HIV antibodies: Tony Floyd (19 February 2003)

Re: HIV antibody test is the Achilles heel of AIDS Inc.: Dr JK Anand (19 February 2003)

Exactly what data suggests HIV-1 and/or HIV-2 ELISAs are not accurate?: Brian T Foley (21 February 2003)

Do not be seduced by the sirens of dissidence: Peter J Flegg (21 February 2003)

Apologies. HIV Testing Was Also Accurate 15 Years Ago: Tony Floyd (22 February 2003)

Reply to Floyd and Foley: David Rasnick (23 February 2003)

Do AIDS drugs deserve credit for extending life?: David Rasnick (23 February 2003)

Rasnick has already PUBLISHED that HIV can be transmitted by sex.: Tony Floyd (24 February 2003)

AIDS and drugs - a response to David Rasnick: Peter J Flegg (24 February 2003)

Scientists must always be able to change their minds: David Rasnick (24 February 2003)

Foley has never cited Genetica. Why did you change your mind again?: Tony Floyd (25 February 2003)

I stand corrected: David Rasnick (26 February 2003)

Duesberg Must Have Also Changed His Mind.: Tony Floyd (26 February 2003)

The anti-HIV drugs: David Rasnick (26 February 2003)

HIV drugs fail in children: David Rasnick (27 February 2003)

Non-specific therapeutic effects of protease inhibitors: Richard G Fiddian-Green (27 February 2003)

comments on debate: Carl Williams (27 February 2003)

HIV - from lethal into a chronic infection with drugs: Tony Floyd (27 February 2003)

Do HIV drugs do more harm than good?: Peter J Flegg (28 February 2003)

Another round of reference checking reveals more holes in AIDS-Denialist argument: Tony Floyd (28 February 2003)

Re: comments on debate: Peter Morrell (1 March 2003)

Time to Try and See the Forest Inspite of the Trees. Checking Common References.: Tony Floyd (1 March 2003)

Re: comments on debate: Christian Fiala (2 March 2003)

Hooray! I am part of a conspiracy!!!: Tony Floyd (2 March 2003)

HIV/AIDS - there is no "debate": Peter J Flegg (3 March 2003)

Heterosexual transmission and credibility: Christian Fiala (3 March 2003)

Re: Do not be seduced by the sirens of dissidence: Rodney M Richards (3 March 2003)

AIDS. South African Government Now Treating Rather Than Debating the Deadly Disease.: Tony Floyd (4 March 2003)

Diagnostic philosophy and a response to Richards: Peter J Flegg (5 March 2003)

Rakai Project Showed Link Between Viral Load and Heterosexual Transmission: Tony Floyd (5 March 2003)

Re: HIV/AIDS - there is no "debate": Todd Miller (5 March 2003)

The Padian Paper Does NOT Support Alternative AIDS Theories: Tony Floyd (6 March 2003)

Antiretorvirals and risk of foetal brain injury: Richard G Fiddian-Green (6 March 2003)

Survival in HIV-infected children has greatly improved with antiretroviral therapy.: Tony Floyd (7 March 2003)

An abuse of surrogate markers for AIDS: David Rasnick (10 March 2003)

Re: HIV drugs fail children: Peter J Flegg (11 March 2003)

Surrogate markers: Peter J Flegg (11 March 2003)

Fleming and Seligmann do NOT support alternative AIDS theories...: Tony Floyd (11 March 2003)

Re: Diagnostic philosophy and a response to Richards: Rodney M Richards (12 March 2003)

Reply to Flegg: David Rasnick (13 March 2003)

Doctor Meles. Yet another researcher incorrectly cited in support of alternative AIDS theories...: Tony Floyd (13 March 2003)

Zidovudine was shown to decrease mother to infant transmission of HIV by approximately two thirds...: Tony Floyd (14 March 2003)

Re: Doctor Meles. Yet another researcher incorrectly cited in support of alternative AIDS theories..: Rodney M Richards (15 March 2003)

Zidovudine results in a significant and sustained reduction in viral load in HIV positive children.: Tony Floyd (18 March 2003)

Further comments on debate: Carl Williams (18 March 2003)

Findings by Robert Gallo may be added to the list.: Tony Floyd (19 March 2003)

Paediatric HIV - a reply to Rasnick: Peter J Flegg (22 March 2003)

Reply to Flegg's evidence: David Rasnick (24 March 2003)

McSherry's study supports the safety of zidovudine use in pregnancy and in the newborn period.: Tony Floyd (28 March 2003)

Yet more on paediatric HIV infection.: Peter J Flegg (28 March 2003)

Re: Sex has nothing to do with AIDS: Brian T Foley (1 May 2004)

Aids and sex 17 January 2003

Gareth Lloyd,
retired
Manchester M23 1PY
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Re: Aids and sex

It ever mystifies me that research into the incidence of AIDS among drug injectors does not appear to take account of their sexual habits. It is entirely possible and plausible that more frequent drug injectors also have more frequent sexual relationships. Research about drug injectors should quantify and take account of this factor.
Competing interests: None declared

Sex has nothing to do with AIDS 20 January 2003

David Rasnick,
Visiting Scientist, Dept. MCB
UC Berkeley, Berkeley, CA 94720
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Re: Sex has nothing to do with AIDS

Dear Editor,
I challenge Dr. Gareth Lloyd to come up with the names (even one will do) of the persons who are documented to have shown that AIDS (or even HIV) is sexually transmitted. I know of no such study. In fact, the scientific, medical literature is full of evidence that neither AIDS nor HIV is sexually transmitted. It is only assumed that they are.
The results of the world's best scientific study that attempted to measure the efficiency of heterosexual transmission of antibodies to HIV was conducted by Nancy Padian and her colleagues (Padian NS, et al. (1997): Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. Am J Epidemiol 146: 350-7).
The most striking result of the ten-year study is that Padian et al. did not observe any HIV-negative sex partners becoming HIV-positive from years of unprotected sexual intercourse with their HIV-positive partners. I repeat�NOT ONE HIV-negative sex partner became positive during the 10- year study. Therefore, the observed transmission efficiency was ZERO.
However, to avoid reporting a zero efficiency for the sexual transmission of HIV, Padian and colleagues assumed that the HIV-positive sex partners in their study must have become positive through sexual intercourse before entering the study. Using that assumption, they estimated that an HIV-negative woman would have to have sexual intercourse 1000 times with HIV-positive men before becoming HIV-positive herself. Even more astounding, HIV-negative men would have to have 8000 sexual contacts before becoming HIV-positive. Virtually identical figures have been reported by others (Gisselquist, D., et al., HIV infections in sub- Saharan Africa not explained by sexual or vertical transmission. Int J STD AIDS, 2002. 13: p. 657-666; Jacquez, J.A., et al., Role of the primary infection in epidemics of HIV infection in gay cohorts. J Acquir Immune Defic Syndr, 1994. 7: p. 1169-1184).
Given these figures and that the Centers for Disease Control estimates that one million Americans have antibodies to HIV raises an enormous problem for sexually transmitted HIV. Since there are around 280 million men and women in the USA, that means that on average an HIV- negative woman would have to have random sexual intercourse 140,000 times (and a man eight times that number) in order to become HIV-positive (assuming equal distribution of HIV between the sexes).
Below are additional examples in the literature that neither AIDS nor HIV is sexually transmitted.
None of the husbands of HIV positive women became antibody positive to HIV over a three-year period. (Lancet ii: 581 (1985), Stewart et al.}
No transmission of HIV was observed between couples in which all of the women were HIV positive and in which at least 100 sexual contacts occurred. (JAMA 259: 3037 (1988), Padian et al.)
After a mean of 3-1/2 years of unprotected intercourse, with an average of 50 sexual encounters per year, only one hemophiliac wife became HIV positive. (American Journal of Medicine 85: 472 (1988), Kim et al.)
No transmission of T-cell abnormalities from hemophiliacs with AIDS to their spouses. (JAMA 251: 1450 (1984), Kreiss et al.)
"The number of American and European heterosexuals who have had sexual relations with a prostitute, who have no other admitted risk factors (such as drug abuse), and who have subsequently developed antibody to HIV can be counted on the fingers of one hand. Sex with a prostitute is not even listed as a risk category by the American CDC." (Rethinking AIDS, Root-Bernstein (1993))
"Non-drug abusing prostitutes have no higher risk of AIDS than other women." (AIDS: the second decade, report from the National Academy of Sciences USA (1990))
The same is true for prostitutes in Germany, Zurich, Vienna, London, Paris, Pardenone (Italy), and Athens. (Klinische Wochenschrift 65: 287 (1987), Luthy et al.; Wiener Klinische Wochenschrift 98: 697 (1986), Kopp & Dangl-Erlach; Lancet ii: 1424 (1985), Brenky-Fandeux & Fribourg- Blanc; British Medical Journal 297: 1585 (1988), Day et al.; Scand J Infect Dis 21: 353 (1988), Hyams et al.)
The repeated appearance between AIDS (antibodies to HIV) in drug users around the world is no coincidence (Duesberg, P.H. and D. Rasnick, The AIDS dilemma: drug diseases blamed on a passenger virus. Genetica, 1998. 104: p. 85-132).
David Rasnick, PhD
Member of Mbeki's AIDS Advisory Panel
Visiting Scientist
Dept. Molecular & Cell Biology, University of California at Berkeley, Berkeley, CA 94720
Competing interests: � None declared

Let us call a spade a spade 21 January 2003

Richard G Fiddian-Green,
None
None
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Re: Let us call a spade a spade

Having had little joy of finding first hand evidence of an "AIDS" epidemic in South Africa (1)it is evident that "AIDS" means very different things to different people.
Kilby and Saag observe that "AIDS" (their quotation marks)has "little clinical utility"(2). "AIDS" is defined by The Center for Disease Control and Prevention in Atlanta as one or more AIDS-defining conditions and a CD4 count less than 200cells/mm2. These are classed A, asymptomatic patients, B, "ARC", and C, AIDS-defining. Class B includes patients with common conditions such as recurrent vaginal candidiasis, cervical dysplasia, and peripheral neuropathy. Class C include patients with TB, cervical cancer, recurrent pneumonias, lymphoma, leukaemia and Salmonellosis. What rural African opulation does not have these? Other patients in class C have the more exotic pulmonary infections and Kaposi's sarcoma. These conditions have been found in African populations for generations.
These diseases reprsent the spectrum of dieases that have been present in African populations for decades before the advent of HIV infections. There are, furthermore, many causes of a abnormally low CD 4 count other than HIV. The diagnosis of "AIDS" is therefore a political definition that encompasses those diseases prevalent in countries with poor socioeconomic circumstances. It is said to be sexually transmitted but from the evidence I have seen it is a questionable and more importantly insignificant cause of the morbidity and mortality in African populations. Surely saying otherwise undermines the integrity of our profession especially if the real purpose is to limit promiscuity and illigitimate births.
1. HIV/AIDS: the biggest error? Richard G Fiddian-Green bmj.com/cgi/eletters/320/7237/0#7270, 4 Apr 2000
2. Kilby JM, Saag MS. Natural history of HIV-1 disease. In Textbook of Aids Medicine, Williams-Wilkens, Baltimore, 1999.
Competing interests: � None declared

Sex has plenty to do with AIDS, at least in sub-Saharan Africa 21 January 2003

Colin D Butler,
Post Doctoral Fellow
National Centre for Epidemiology & Population Health, Canberra Australia 0200
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Re: Sex has plenty to do with AIDS, at least in sub-Saharan Africa

Lack of male circumcision and genital ulceration (also increased in uncircumcised men) are important risk factors for heterosexual HIV transmission (1,2). These factors are likely to be far less common among the populations listed by Dr Rasnick as counter-examples to the hypothesis that HIV is transmitted heterosexually . However, I agree that the risk of heterosexual transmission of HIV from or to circumcised men without genital ulcers was initially overstated.
1. Weiss H, Quigley MA, Hayes, RJ. Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis AIDS 2000; 14: 2361-2370.
2. Halperin DT, Bailey RC. Male circumcision and HIV infection: 10 years and counting Lancet 1999; 354: 1813-1815.
Competing interests: None declared

HIV-1 and HIV-2 are sexually transmitted lentiviruses 24 January 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: HIV-1 and HIV-2 are sexually transmitted lentiviruses

There are thousands of peer-reviewed published reports of the heterosexual and homosexual transmission of HIV-1 and HIV-2. Studies designed to determin the exact frequency of transmission via UNPROTECTED intercourse would be unethical and illegal. However, hundreds of studies have shown that unprotected intercourse frequently results in transmission of HIV-1. Some examples:
1) Nushawn Williams infected 13 of the 42 young women he had unprotected sex with, as published in AIDS Res Hum Retroviruses 2002 Oct 10;18(15):1157-61 Molecular analysis in support of an investigation of a cluster of HIV-1-infected women.
Robbins KE, Weidle PJ, Brown TM, Saekhou AM, Coles B, Holmberg SD, Folks TM, Kalish ML. PMID: 12402955
2) A Haitian man who moved to Sweden in 1980 transmitted the virus to 6 of the 8 women he had sexual relationships with as published in Leitner T, Escanilla D, Franzen C, Uhlen M, Albert J Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10864-9. PMID: 8855273
3) A man who sexually assaulted a 12 year old girl was convicted not only of assault, but also of transmitting HIV to her as published in Machuca R, Jorgensen LB, Theilade P, Nielsen C Molecular investigation of transmission of human immunodeficiency virus type 1 in a criminal case. Clin Diagn Lab Immunol. 2001 Sep;8(5):884-90. PMID: 11527797
4) Sexual transmission spread HIV-1 beyond the initial transfusion recipients as described in Diaz RS, Zhang L, Busch MP, Mosley JW, Mayer A. Divergence of HIV-1 quasispecies in an epidemiologic cluster. AIDS. 1997 Mar 15;11(4):415-22. PMID: 9084787
These are just a very few of the thousands of very well documented cases of heterosexual transmission of HIV-1 and HIV-2. There are tens of millions of less well documented cases.
Brian Foley, PhD
HIV Genetic Sequences and Immunology Databases
http://hiv-web.lanl.gov/
Competing interests: � None declared

Correction Re: HIV-1 and HIV-2 are sexually transmitted lentiviruses 24 January 2003

Brian T Foley,
HIV Reasercher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Correction Re: HIV-1 and HIV-2 are sexually transmitted lentiviruses

Example 3: Clin Diagn Lab Immunol. 2001 Sep;8(5):884-90. Was actually a case of homosexual transmission from a man to a 12 year old boy, not heterosexual from man to girl.
Better examples of the scientific reporting of sexual transmission as opposed to the legal and sensational reporting of sexual transmission of HIV-1 are:
Trask SA, Derdeyn CA, Fideli U, Chen Y, Meleth S, Kasolo F, Musonda R, Hunter E, Gao F, Allen S, Hahn BH. Molecular epidemiology of human immunodeficiency virus type 1 transmission in a heterosexual cohort of discordant couples in Zambia. J Virol. 2002 Jan;76(1):397-405. PMID: 11739704
Fideli US, Allen SA, Musonda R, Trask S, Hahn BH, Weiss H, Mulenga J, Kasolo F, Vermund SH, Aldrovandi GM. Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa. AIDS Res Hum Retroviruses. 2001 Jul 1;17(10):901-10. PMID: 11461676
Skurnick JH, Kennedy CA, Perez G, Abrams J, Vermund SH, Denny T, Wright T, Quinones MA, Louria DB. Behavioral and demographic risk factors for transmission of human immunodeficiency virus type 1 in heterosexual couples: report from the Heterosexual HIV Transmission Study. Clin Infect Dis. 1998 Apr;26(4):855-64. PMID: 956446
van Harmelen J, Wood R, Lambrick M, Rybicki EP, Williamson AL, Williamson C. An association between HIV-1 subtypes and mode of transmission in Cape Town, South Africa. AIDS. 1997 Jan;11(1):81-7. PMID: 9110079
Kane CT, Montavon C, Toure MA, Faye MA, Ndiaye AG, Diallo AG, Ndoye I, Liegeois F, Delaporte E, Mboup S, Peeters M. Full-length genome sequencing of HIV type 1 group O viruses isolated from
a heterosexual transmission cluster in Senegal. AIDS Res Hum Retroviruses. 2001 Aug 10;17(12):1211-6. PMID: 11522190
Nelson KE, Rungruengthanakit K, Margolick J, Suriyanon V, Niyomthai S, de Boer MA, Kawichai S, Robison V, Celentano DD, Nagachinta T, Duerr A. High rates of transmission of subtype E human immunodeficiency virus type 1 among heterosexual couples in Northern Thailand: role of sexually transmitted diseases and immune compromise. J Infect Dis. 1999 Aug;180(2):337-43. PMID: 10395847
Delwart EL, Busch MP, Kalish ML, Mosley JW, Mullins JI. Rapid molecular epidemiology of human immunodeficiency virus transmission. AIDS Res Hum Retroviruses. 1995 Sep;11(9):1081-93. PMID: 8554905
Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, Meehan MO, Lutalo T, Gray RH. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000 Mar 30;342(13):921-9. PMID: 10738050
Hayman A, Moss T, Simmons G, Arnold C, Holmes EC, Naylor-Adamson L, Hawkswell J, Allen K, Radford J, Nguyen-Van-Tam J, Balfe P. Phylogenetic analysis of multiple heterosexual transmission events involving subtype b of HIV type 1. AIDS Res Hum Retroviruses. 2001 May 20;17(8):689-95. PMID: 11429109
Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, vanCott T, Quinn TC. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet. 2001 Apr 14;357(9263):1149-53. PMID: 11323041
Jonassen TO, Grinde B, Asjo B, Hasle G, Hungnes O. Intersubtype recombinant HIV type 1 involving HIV-MAL-like and subtype H-like sequence in four Norwegian cases. AIDS Res Hum Retroviruses. 2000 Jan 1;16(1):49-58. PMID: 10628816
Yirrell DL, Pickering H, Palmarini G, Hamilton L, Rutemberwa A, Biryahwaho B, Whitworth J, Brown AJ. Molecular epidemiological analysis of HIV in sexual networks in Uganda. AIDS. 1998 Feb 12;12(3):285-90. PMID: 9517991
Competing interests: None declared

Canadian aboriginals in Vancouver face AIDS epidemic 25 January 2003

James E Parker,
retired Paediatrician
289 McCallum Rd Abbotsford B.C CANADA
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Re: Canadian aboriginals in Vancouver face AIDS epidemic

A fascinating discussion appears to be developing concerning the above news item.
In electronic musings Gareth Lloyd ('Aids and sex' - 17 Jan 2003) wonders about the degree of sexual promiscuity in drug injectors. David Rasnick ( 'Sex has nothing to do with AIDS' - 20 Jan 2003 ) responds asking for names ( even one will do ). He knows of no studies which have medically documented that HIV is sexually transmitted.
Richard G Fiddian-Green, ('Let us call a spade a spade' -21 Jan 2003 ) who has had little joy finding first hand evidence of an "AIDS" epidemic in South Africa, feels that it is all a matter of semantics. "AIDS" he states is a political definition.
'Sex has had plenty to do with AIDS at least in sub Saharan Africa' states Colin D Butler ( 21 Jan 2003 ) citing lack of male circumcision and genital ulceration as important risk factors in heterosexual HIV transmission.
' HIV-1 and HIV-2 are sexually transmitted lentiviruses ' states Brian T Foley in his letter and correction ( 24 Jan 2003 ). Citing names, cases, clusters and situations his communications would appear 'to put the boots' to the arguments presented by Dr's Rasnick and Fiddian Green.
Returning to the topic of the news item in question. - Why do aboriginals in Vancouver face an AIDS epidemic ?. I believe the answer to this rests with the provincial department of public health. In Dec 2002 the Reportable diseases in British Columbia are listed in the BC Nedical Journal by the Centre for Disease Control. Schedule A, reportable by all sources lists over 80 conditions from Anthrax to Yellow Fever (including Syphilis, Chancroid and Gonorrhea ). Schedule B, reportable by laboratories only, lists various organisms. HIV is not on either list !.
Can it be that HIV is not reportable in this province because it is considered a non-disease ?.
James E Parker
Competing interests: None declared

Let�s scrutinize the evidence 26 January 2003

David Rasnick,
Visiting Scientist, Dept. MCB
UC Berkeley, Berkeley, CA 94720
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Re: Let�s scrutinize the evidence

Brian Foley does indeed provide a list of references where the titles seem to indicate that HIV is sexually transmitted. However, if you lay your hands on the papers you will discover that the authors assumed that HIV is sexually transmitted and that their studies were not designed to actually determine if that assumption is true. Also notice the high proportion of recent references to Africa, where sexual transmission is assumed. Why are there no references to the 1980s, where the evidence for sexual transmission should exist if it does? On what basis did scientists and doctors believe that AIDS or HIV was sexually transmitted in those days? In other words, what is the foundation for the assumption of sexual transmission of HIV in Foley's references?
I'm not as ready to accept titles of papers, as James Parker appears to be, as proof of anything. I am eager to scrutinize any specific example or two that Foley cares to use as proof that HIV or AIDS is sexually transmitted. We can discuss the evidence for and against by quoting from the papers he cites to see if it does indeed justify and support the titles, conclusions and assumptions.
So, are you (Brian Foley) willing to put the sexual transmission of HIV or AIDS on trial? Are you prepared to scrutinize the evidence presented in the references you put forth as proof that HIV or AIDS are sexually transmitted?
Dave
Competing interests: None declared

Re: Let�s scrutinize the evidence 28 January 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Re: Let�s scrutinize the evidence

Whether or not the studies I cited were designed to "prove" that HIV- 1 and HIV-2 can be sexually transmitted, they do provide compelling evidence that these lentiviruses are indeed sexually transmitted.
Before going off to "scrutinize" all of the papers I cited, Dr. Rasnick should re-evaluate his interpretations of the paper he started with. Citing one of Dr. Nancy Padian's papers, David wrote:
"The results of the world's best scientific study that attempted to measure the efficiency of heterosexual transmission of antibodies to HIV was conducted by Nancy Padian and her colleagues (Padian NS, et al. (1997): Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. Am J Epidemiol 146: 350-7).
The most striking result of the ten-year study is that Padian et al. did not observe any HIV-negative sex partners becoming HIV-positive from years of unprotected sexual intercourse with their HIV-positive partners. I repeat�NOT ONE HIV-negative sex partner became positive during the 10- year study. Therefore, the observed transmission efficiency was ZERO. "
In reality, the abstract and text of that paper state that there were 70 seroconversions during the ten-year period:
"Overall, 68 (19%) of the 360 female partners of HIV-infected men (95% confidence interval (CI) 15.0-23.3%) and two (2.4%) of the 82 male partners of HIV-infected women (95% CI 0.3-8.5%) were infected. "
How does Dr. Rasnick get from 70 (68 + 2) to ZERO?
Dr. Rasnick goes on to state: "Given these figures and that the Centers for Disease Control estimates that one million Americans have antibodies to HIV raises an enormous problem for sexually transmitted HIV. Since there are around 280 million men and women in the USA, that means that on average an HIV- negative woman would have to have random sexual intercourse 140,000 times (and a man eight times that number) in order to become HIV-positive (assuming equal distribution of HIV between the sexes)."
What twisted mathematics does Dr. Rasnick believe in? Does he also believe that if auto accidents occur on average once for every 10,000,000 miles driven that we are all 100% safe until we have driven more than 10,000,000 miles? Even if the odds of infection (or auto accident) are low, the odds of becoming infected during the very first sex act (or having an accident suring the first 100 miles driven) are not ZERO. Nobody has to have sex 100 or 140,000 times in order to become infected, if can and does happen quite often during the very first act.
Rather than "scrutinizing" the papers that I presented, Dr. Rasnick should have a look at the twisted logic an mathematics required to "re- think" AIDS into a problem that does not involve sex. Occam's razor is often a useful tool.
Competing interests: � Personally disgusted by the lies that "rethinkers" are willing to tell in order to attamtp to convince people that AIDS is not a problem caused by the HIV-1 and HIV-2 lentiviruses.

Foley wants to scrutinize Padian et al. first 29 January 2003

David Rasnick,
Visiting Scientist Dept. MCB
UC Berkeley, CA 94720
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Re: Foley wants to scrutinize Padian et al. first

"Before going off to 'scrutinize' all of the papers I cited," Foley says, "Dr. Rasnick should re-evaluate his interpretations of the paper he started with. Citing one of Dr. Nancy Padian's papers". Very well, let the analysis begin with the Padian et al. study that I have submitted as evidence against the sexual transmission of HIV. (Padian, N.S., et al., Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. Am J Epidemiol, 1997. 146(4): p. 350-7)
In attempting to refute my evidence that the Padian et al. study showed zero sexual transmission of antibodies to HIV, Foley quotes from the abstract of their paper and says that, "In reality, the abstract and text of that paper state that there were 70 seroconversions during the ten -year period": 'Overall, 68 (19%) of the 360 female partners of HIV- infected men (95% confidence interval (CI) 15.0-23.3%) and two (2.4%) of the 82 male partners of HIV-infected women (95% CI 0.3-8.5%) were infected.'"
So, now Foley moves from the titles of papers as proof that HIV is sexually transmitted to quoting from an abstract. However, let us examine the Padian et al. paper in more depth and see if it provides sufficient justification for both the title and claims in the abstract. In short, do the results of the Padian et al. study provide evidence, strong or otherwise, to support the hypothesis that HIV is sexually transmitted.
On page 351, Padian et al. specifically say that, "given the retrospective nature of the cross-sectional aspect of our design (e.g., transmission occurred prior to entry in the study), past infection is probably a more appropriate measure for the cross-sectional analysis. A prospective phase of the study began in 1990. After entry, serodiscordant couples who remained together were seen every 6 months for an interview covering the interval since the last visit and physical examination with the same laboratory tests described above."
Then on page 352 they state: "The infectivity constant (per-contact transmission risk) for male-to-female transmission was estimated using maximum likelihood methods taking into account of the fact that infection times of both index cases and all infected partners occurred prior to recruitment and are known only to lie in broad intervals (11). These intervals were defined by the reported lengths of exposure for couples and the earliest possible time of infection for the index cases. The plausibility of the assumption that infectivity is constant was evaluated using methods described in Shiboski and Jewell (12) and Shiboski (13)."
The 68 females and 2 males that Foley extracts from the abstract of Padian et al. come from the "retrospective...cross-sectional" part of their study on page 352 under Cross-sectional rsults, where the authors admit that they assumed that these people became HIV positive through sex before entry into the study.
However, on page 354 from the "Prospective results", where the authors attempted to document actual sexual transmission of antibodies to HIV, they state: "We followed 175 HIV-discordant couples over time, for a total of approximately 282 couple-years of follow-up (table 3). Because of deaths as well as the break-up of couples, attrition was severe; only 175 couples are represented in table 3. The longest duration of follow-up was 12 visits (6 years). We observed no seroconversion after entry into the study."
Finally, in the discussion section on page 356 the authors say this: "While our estimation procedure does not require that infection time be observed [which is admitted to be the case], it does depend on the assumptions of constant rates and parametric forms for infectivity. (We assumed that the infectivity was either constant, linearly increasing, or linearly decreasing with time following index case infection. Direct non- parametric estimation of this quantity is problematic in the absence of information on when the index case became infected (9)."
"While lack of transmission in our prospective study may in part be due to...unidentified protective factors, we also observed significant behavior change over time. ...Nevertheless, the absence of seroincident infection over the course of the study cannot be entirely attributed to significant behavior change. No transmission occurred among 25 percent of couples who did not use condoms consistently at their last follow-up nor among the 47 couples who intermittently practiced unsafe sex during the entire duration of follow-up."
Foley asked: "How does Dr. Rasnick get from 70 (68 + 2) to ZERO?" The answer is simple. I take the authors own results of zero observations of sexual transmission to be just that--zero.
Finally, Foley says that he is "Personally disgusted by the lies that 'rethinkers' are willing to tell in order to attamtp [sic] to convince people that AIDS is not a problem caused by the HIV-1 and HIV-2 lentiviruses."
Can Foley be more specific about which lies I have told?
David Rasnick
Competing interests: None declared

Re: Foley wants to scrutinize Padian et al. first 30 January 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
Send response to journal:
Re: Re: Foley wants to scrutinize Padian et al. first

David Rasnick says:
"Foley asked: "How does Dr. Rasnick get from 70 (68 + 2) to ZERO?" The answer is simple. I take the authors own results of zero observations of sexual transmission to be just that--zero. "
Yet his original statement was:
" I repeat�NOT ONE HIV-negative sex partner became positive during the 10- year study."
In reality, the ten year study included both the retrospective portion in which there were 70 seroconversions and the prospective portion in which condoms were more consistently used and no seroconverstions were observed. The longest observation period was one couple that was observed for six years. So 70 seroconversions occurred during the 10-year period, zero in the more recent years after counselling to avoid unsafe sex was started.
David Rasnick says:
" Finally, Foley says that he is "Personally disgusted by the lies that 'rethinkers' are willing to tell in order to attamtp [sic] to convince people that AIDS is not a problem caused by the HIV-1 and HIV-2 lentiviruses."
Can Foley be more specific about which lies I have told? "
David Rasnick and Peter Duesberg are both very careful to avoid telling blatant lies. Instead they only twist the truth such that other "rethinkers" end up telling lies when misquoting them. In this case, David Rasnick states that no seroconversions were observed during the entire ten years of the Padian study, and this is true, the seroconversions were not "directly observed". But many people misquote such statements to claim that Padian's study actually followed the people for the ten-year period and did not observe any seroconversions.
In another example: http://bmj.com/cgi/eletters/326/7381/126/e#29221 David states:
" However, there is no proof in the scientific, medical literature that the anti-HIV drugs do more good than harm, even in the developed world [2]. Indeed, the opposite is true. "
The first statement, about no "proof" that HAART does more harm than good, is highly dependent on what one considers "proof" to be. I suspect that no data will ever be "proof" enough for David Rasnick, but I feel that it is misleading to cite one paper by Peter Duseberg and imply that there is evidence that HAART does more harm than good. Here are just a few of the thousands of papers which imply that there is a clear benefit:
Resino S, Bellon JM, Sanchez-Ramon S, Gurbindo D, Ruiz-Contreras J, Leon JA, Ramos JT, Munoz-Fernandez MA. Impact of antiretroviral protocols on dynamics of AIDS progression markers. Arch Dis Child. 2002 Feb;86(2):119-24. PMID: 11827906 RESULTS: No child in the HAART group progressed to AIDS, whereas 14 children in the NT and seven in the MT groups progressed to AIDS, respectively, the differences being statistically significant. CONCLUSION: Potent ART had the greatest protective effect against progression to AIDS in this observational study.
Baum SE, Morris JT, Gibbons RV, Cooper R. Reduction in human immunodeficiency virus patient hospitalizations and nontraumatic mortality after adoption of highly active antiretroviral therapy. Mil Med. 1999 Sep;164(9):609-12. PMID: 10495628 Comparing 1997 with 1994 and 1995, we found a greater than 700% increase in the average expenditure on antiretroviral agents after institution of HAART. At the same time, we found a dramatic reduction in hospitalizations and nontraumatic mortality. Therefore, the increase in expenditures on antiretroviral agents may be offset by a reduction in hospitalizations and mortality.
Eron JJ Jr. HIV-1 protease inhibitors. Clin Infect Dis. 2000 Jun;30 Suppl 2:S160-70. Review. PMID: 10860901 Treatment of human immunodeficiency virus type 1 (HIV-1) infection with regimens that include protease inhibitors (PIs) has contributed to marked improvements in HIV-related disease progression and mortality.
Tavel JA Ongoing trials in HIV protease inhibitors. Expert Opin Investig Drugs. 2000 Apr;9(4):917-28. Review. PMID: 11060719 What was once a uniformly fatal syndrome has become a more treatable, chronic, infectious disease. Central to this revolution have been the protease inhibitors, a class of drugs with potent antiretroviral activity.
Nuesch R, Geigy N, Schaedler E, Battegay M. Effect of highly active antiretroviral therapy on hospitalization characteristics of HIV-infected patients. Eur J Clin Microbiol Infect Dis. 2002 Sep;21(9):684-7. PMID: 12373504 Since the advent of HAART, the yearly number of admissions related to HIV dropped by 49% and HAART was administered often during hospital stay. By the end of the study period, death due to multiple HIV-associated diseases and wasting had disappeared.
Arici C, Ripamonti D, Ravasio V, Maggiolo F, Rizzi M, Finazzi MG, Suter F. Long-term clinical benefit after highly active antiretroviral therapy in advanced HIV-1 infection, even in patients without immune reconstitution. Int J STD AIDS. 2001 Sep;12(9):573-81. PMID: 11516366
Gerard L, Galicier L, Boulanger E, Quint L, Lebrette MG, Mortier E, Meignin V, Oksenhendler E. Improved survival in HIV-related Hodgkin's lymphoma since the introduction of highly active antiretroviral therapy. AIDS. 2003 Jan 3;17(1):81-7. PMID: 12478072
Wood E, Montaner JS, Chan K, Tyndall MW, Schechter MT, Bangsberg D, O'Shaughnessy MV, Hogg RS. Socioeconomic status, access to triple therapy, and survival from HIV- disease since 1996. AIDS. 2002 Oct 18;16(15):2065-72. PMID: 12370506
Heard I, Tassie JM, Kazatchkine MD, Orth G. Highly active antiretroviral therapy enhances regression of cervical intraepithelial neoplasia in HIV-seropositive women. AIDS. 2002 Sep 6;16(13):1799-802. PMID: 12218392
Leonard MK, Larsen N, Drechsler H, Blumberg H, Lennox JL, Arrellano M, Filip J, Horsburgh Jr CR. Increased survival of persons with tuberculosis and human immunodeficiency virus infection, 1991--2000. Clin Infect Dis. 2002 Apr 1;34(7):1002-7. PMID: 11880967
David States:
"Dr. Amy Justice of the University of Pittsburgh told her colleagues at the 14th International AIDS Conference in Barcelona this year that the most common cause of death among HIV positive people is not AIDS but liver failure due to the drugs [4]. "
Her abstract was about liver enzymes in HIV infections, but I could not find a statement in the on-line version cited: http://www.aids2002.com/Program/ViewAbstract.asp?id=/T- CMS_Content/Abstract/200206290750522147.xml that said that liver failure due to drugs offset the anti-HIV benefits of the drugs. Many HIV-infected people are also co-infected with hepatitis viruses and have other risk factors for liver damage. Some of the antiretrovirals can cause liver damage, but even so the reduction in deaths due to AIDS more than offsets the risk of death due to liver damage from those drugs.
Even if all of the deaths in her study were due to drug-induced liver failure and not viral-induced liver failure or AIDS, the drugs may stilll be beneficial if they prevented more AIDS deaths than they caused in liver failure deaths. If Amy Justice is convinced that antiretroviral drugs are so much more dangerous than untreated HIV infection, why has she never published a paper of letter to the editor stating this?
Competing interests: � None declared

Checking Rasnick's Citations showing HIV not transmitted sexually. 30 January 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
Send response to journal:
Re: Checking Rasnick's Citations showing HIV not transmitted sexually.

David Rasnick wrote:
" Below are additional examples in the literature that neither AIDS nor HIV is sexually transmitted.
None of the husbands of HIV positive women became antibody positive to HIV over a three-year period. (Lancet ii: 581 (1985), Stewart et al.} "
In fact this Stewart paper was one of the first to show that HIV-1 (named HTLV-III at that time) could indeed be transmitted by semen:
Lancet 1985 Sep 14;2(8455):581-5
Transmission of human T-cell lymphotropic virus type III (HTLV-III) by artificial insemination by donor.
Stewart GJ, Tyler JP, Cunningham AL, Barr JA, Driscoll GL, Gold J, Lamont BJ.
Four of eight recipients of artificial insemination (AI) with cryopreserved semen from a symptomless carrier of human T-cell lymphotropic virus type III (HTLV-III) were found to have antibody to the virus. One has generalised, persistent lymphadenopathy while the other three remain symptom free 3 years after insemination. Three subsequently became pregnant more than a year after contact with the infected semen; the children, who are now over 1 year of age, are in good health and do not have HTLV-III antibodies. These observations emphasise the need for a rigorous screening programme for potential AI donors; they also suggest that fresh semen should not be used in AI. The findings confirm the role of semen in heterosexual transmission of the virus and suggest that in women with HTLV-III antibodies pregnancy and subsequent breast-feeding does not necessarily lead to infection of the infant. PMID: 2863597
" No transmission of HIV was observed between couples in which all of the women were HIV positive and in which at least 100 sexual contacts occurred. (JAMA 259: 3037 (1988), Padian et al.) "
I can't find the JAMA paper by Padian, the pages cited were authored by Jay Levy:
Levy JA
The transmission of AIDS: the case of the infected cell. JAMA. 1988 May 27;259(20):3037-8. PMID: 3285042
But by 1988 Nancy Padian had already published many papers which strongly suggested (I'll leave the word "proof" to you) that HIV-1 was indeed sexually transmitted:
JAMA 1987 Aug 14;258(6):788-90
Male-to-female transmission of human immunodeficiency virus.
Padian N, Marquis L, Francis DP, Anderson RE, Rutherford GW, O'Malley PM, Winkelstein W Jr.
Ninety-seven female sexual partners of 93 men infected with human immunodeficiency virus were studied. All of the women had sexual contact within the year before their partner had been diagnosed as having acquired immunodeficiency syndrome or was found to have a positive reaction on the human immunodeficiency virus serologic test. Fifty-seven percent were the partners of bisexual men. Overall, 23% of the women were infected (95% confidence interval, 15% to 32%). The total number of exposures to the index case (sexual contacts with ejaculation) and the specific practice of anal intercourse, also with the infected partner, were associated with transmission. Neither condom use, total number of sexual partners since 1978, nor lifetime number of sexually transmitted diseases was associated with infection. PMID: 3475478
" After a mean of 3-1/2 years of unprotected intercourse, with an average of 50 sexual encounters per year, only one hemophiliac wife became HIV positive. (American Journal of Medicine 85: 472 (1988), Kim et al.) "
This is correct, but it should be noted that the study only involved 14 couples, so 1:14 = 7% seroconverted during the study, and all 14 couples were counselled to use condoms. This study shows that safe sex is relatively safe, but does not prove that HIV cannot be sexually transmitted.
I find it odd that David Rasnick claims that these papers provide compelling evidence (if not proof) that HIV cannot be sexually transmitted. I read the same papers and come to the opposite conclusion.
We obviously both can't be right.
Competing interests: � None declared

Still no sexual transmission of HIV, let alone AIDS 31 January 2003

David Rasnick,
Visiting Scientist Dept. MCB
UC Berkeley, Berkeley, CA 94720
Send response to journal:
Re: Still no sexual transmission of HIV, let alone AIDS

Foley concedes that, "during the entire ten years of the Padian study...the seroconversions were not 'directly observed'." That's exactly what I said the Padian et al. study showed. The people who had antibodies to HIV when they entered the study were assumed to have become HIV positive previously through sexually intercourse. Foley accepts that assumption as fact. I am simply asking what is the evidence in the scientific, medical literature that justifies making that assumption. The Padian et al. study does not provide that evidence. So, now let's move on to where Foley says that evidence can be found.
Foley says that the Stewart paper I cited "was one of the first to show that HIV-1 (named HTLV-III at that time) could indeed be transmitted by semen" (Lancet 1985 Sep 14;2(8455):581-5). Again, as with the Padian et al. study, the title and abstract would lead one to believe that HIV (HTLV -III) is sexually transmitted. Foley quotes from the abstract: "Four of eight recipients of artificial insemination (AI) with cryopreserved semen from a symptomless carrier of human T-cell lymphotropic virus type III (HTLV-III) were found to have antibody to the virus." However, the mere presence of antibodies to HIV in those women was assumed to result from the transmission of HIV through artificial insemination. But there is a serious problem with this assumption. The Abbott ELISA test for antibodies to HIV did not become available in Australia until April 1985 and the Stewart et al. paper was published in September 1985. Consequently, the women were not tested prior to artificial insemination for antibodies to HIV. Therefore, there is no way of knowing if they became antibody positive as a result of artificial insemination--or any other way for that matter.
To complicate matters even further, there are over 60 documented ways a person can have antibodies to HIV who has never been exposed to the virus--and one of those is pregnancy. I can provide the references if requested. Also, the first Abbott ELISA test for antibodies to HIV had false positive rates of 50% and higher. The reason for the extremely high false-positive rates was because the FDA approved the test to screen the blood supply. The ELISA antibody test has never been approved to diagnose AIDS or HIV infection. And, amazingly enough, the insert that comes with the Abbott ELISA test states that, "At present, there is no recognized standard for establishing the presence and absence of HIV-1 antibody in human blood" (Human Immunodeficiency Virus Type 1, HIVAB HIV-1 EIA, 1995, Abbott Laboratories, Diagnostics Division, 66-8805/R5). In other words, it is not known whether the Abbott ELISA test is even detecting antibodies to HIV.
Regardless of how the women came to have antibodies against HIV, none of the husbands of the four HIV-seropositive women developed antibodies against HIV over a three-year period involving extensive and regular sexual relations without barrier methods of contraception. All the children are antibody negative and healthy. This is hardly convincing evidence that HIV or even antibodies to HIV are sexually transmitted.
Foley says that, "[he] can't find the JAMA paper by Padian, the pages cited were authored by Jay Levy, The transmission of AIDS: the case of the infected cell. JAMA. 1988 May 27;259(20):3037-8". That is true, the paper is authored by Levy, who discusses previously unpublished data from Nancy Padian and Warren Winkelstein. My apologies for not listing Levy as the author, but the facts remain: "In [a] study involving 12 couples, no transmission from the infected woman to the male partner occurred after often more than 100 sexual contacts".
Foley says that it was "strongly suggested" in the Padian et al. 1987 paper "that HIV-1 was indeed sexually transmitted" (JAMA 258 (6), 788-790 (1987)). However, this paper provides even less data that the Padian et al. 1997 paper and once again begins with the assumption that HIV is sexually transmitted. The 1987 paper did not study the transmission of HIV but studied women who turned out to have antibodies to HIV, assuming they became positive through sex. Of the 75 women who were HIV-negative when the study began, 30 were retested 6 months after entry and "none had seroconverted". Again, no evidence that HIV or antibodies to HIV are sexually transmitted. Nevertheless, Padian et al. declare that, "Male-to- female sexual transmission of the AIDS virus was clearly documented in this study." I have the paper in front of me and I can't find where they documented (clearly or otherwise) the sexual transmission of the "AIDS virus". Perhaps Foley can direct me to the exact location in the paper where this is documented.
Foley finds "it odd that David Rasnick claims that these papers provide compelling evidence (if not proof) that HIV cannot be sexually transmitted." I find it odd that neither Foley nor anyone else can provide evidence, convincing or otherwise, that HIV is sexually transmitted--much less AIDS itself. Without any scientific foundation, HIV and AIDS are believed to be acquired through sexual intercourse. I use believed because beliefs are things taken to be true in the absence of evidence. Until sufficient evidence--even the beginnings of such evidence--is produced, I will continue to ask why people believe that HIV and AIDS are sexually transmitted.
Brian Foley, we have examined the 1997 Padian et al. study, the longest and most thorough in the field of sexual transmission of HIV, and have found that it does not provide the evidence that HIV is sexually transmitted or is even likely to be sexually transmitted. We have scrutinized lesser studies and found them lacking. However, instead of showing where the evidence for sexual transmission of HIV or even AIDS may be found, you go off in a completely different direction, quoting me as saying that, "there is no proof in the scientific, medical literature that the anti-HIV drugs do more good than harm, even in the developed world [2]. Indeed, the opposite is true." You got the quote right. I did say that and I am prepared to justify that statement by citing and quoting the literature. But let's first get back to the sexual transmission of HIV and finish that discussion before moving on to the other problems with the contagious, HIV hypothesis of AIDS. Can you offer any evidence from the scientific, medical literature that gives the foundation for the prevailing assumption that HIV is sexually transmitted? Are there any studies that actually attempted to determine whether HIV or AIDS can be transmitted sexually? I think you will agree that even if it turns out that HIV can indeed be transmitted sexually that the Padian et al. and numerous other studies indicate that sexual transmission must be highly inefficient. Then one must show that AIDS is sexually transmitted. If you cannot come up with the evidence that I'm seeking, then I guess we can move on to examine whether the anti-HIV drugs do more good than harm.
David Rasnick
Competing interests: None declared

Re: Still no sexual transmission of HIV, let alone AIDS 1 February 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
Send response to journal:
Re: Re: Still no sexual transmission of HIV, let alone AIDS

David Rasnick writes: > But let's first get back to the sexual transmission of HIV and finish that discussion before > moving on to the other problems with the contagious, HIV hypothesis of AIDS. Can > you offer any evidence from the scientific, medical literature that gives the foundation > for the prevailing assumption that HIV is sexually transmitted? Yes. I cited several of the hundreds of peer-reviewed papers that show beyond any reasonable doubt that HIV-1, HIV-2 and other lentiviruses can be and are sexually transmitted. It was your contention that the study by Nancy Padian et al. provided compelling evidence that HIV-1 could not possibly be sexually transmitted, not my contention that her study was the best proof that it can be sexually transmitted. Beyond peer-reviewed publications, one need only interview AIDS patients to get an idea of the risk factors associeated with HIV infection and AIDS. Other sources of information are the court systems, where dozens of people are jailed every year for heterosexual transmission if HIV-1. If David Rasnick or anyone else had truly compelling evidence to doubt that HIV-1 can be sexually transmitted, it would be a crime not to use that evidence to free these people. See for example: http://www.rgj.com/news/printstory.php?id=18847 HIV-positive prostitute gets 6 years for solicitation Martha Bellisle RENO GAZETTE-JOURNAL 7/10/2002 09:31 pm A 33-year-old prostitute who solicited sex, despite having tested positive for the virus that causes AIDS, was sentenced Wednesday to six years in prison. � "South Dakota Man Given 120 Days Jail Time for Knowingly Exposing Woman to HIV" Associated Press (08.29.02) Joe Kafka Nikko Briteramos, 19, was ordered Thursday to spend 120 days in jail for having sex with his girlfriend without revealing that he had HIV. Briteramos, a basketball player at SiTanka-Huron University in Huron, was the first person convicted in South Dakota of intentionally exposing someone to HIV. He could have faced up to 15 years in prison. � http://www.poz.com/archive/august2000/inside/mostunwanted.html America's Most Unwanted by Laura Whitehorn, with research assistance by Illith Rosenblum Sex and HIV. If you have the first without disclosing the second, you can be locked up in Alabama, Arkansas, California, Connecticut, Florida, Georgia, Idaho, Illinois, Indiana, Iowa, Kansas, Louisiana, Maryland, Michigan, Minnesota, Missouri, Montana, Nevada, New Jersey, North Dakota, Ohio, Oklahoma, South Carolina, Tennessee, Texas and Washington. In some states, sex crimes -- even sex work -- can get ratcheted up to attempted murder if HIV is involved, as can spitting or biting. � > Are there any studies that actually attempted to determine whether HIV or AIDS can be > transmitted sexually? I guess that depends on what you call a "study". It seems that retrospective evidence is not good enough to meet your criteria. You seem to be looking for humans to volunteer to have unprotected sex with HIV-seropositive individuals in a controlled scientific setting. Such a study is not ethical or legal, so you can rest assured that such a study could never be published in a peer-reviewed journal. Although many people question the ethics of using primates to test the same hypothesis, primates have indeed been sexually infected with SIVs and SHIVs. Joag SV, Adany I, Li Z, Foresman L, Pinson DM, Wang C, Stephens EB, Raghavan R, Narayan O. Animal model of mucosally transmitted human immunodeficiency virus type 1 disease: intravaginal and oral deposition of simian/human immunodeficiency virus in macaques results in systemic infection, elimination of CD4+ T cells, and AIDS. J Virol. 1997 May;71(5):4016-23. PMID: 9094679 Ambrose Z, Larsen K, Thompson J, Stevens Y, Finn E, Hu SL, Bosch ML. Evidence for early local viral replication and local production of antiviral immunity upon mucosal simian-human immunodeficiency virus SHIV(89.6) infection in Macaca nemestrina. J Virol. 2001 Sep;75(18):8589-96. PMID: 11507204 Harouse JM, Gettie A, Tan RC, Eshetu T, Ratterree M, Blanchard J, Cheng-Mayer C. Pathogenic determinants of the mucosally transmissible CXCR4-specific SHIV(SF33A2) map to env region. J Acquir Immune Defic Syndr. 2001 Jul 1;27(3):222-8. PMID: 11464140 Greenier JL, Miller CJ, Lu D, Dailey PJ, Lu FX, Kunstman KJ, Wolinsky SM, Marthas ML. Route of simian immunodeficiency virus inoculation determines the complexity but not the identity of viral variant populations that infect rhesus macaques. J Virol. 2001 Apr;75(8):3753-65. PMID: 11264364 Smith SM, Baskin GB, Marx PA. Estrogen protects against vaginal transmission of simian immunodeficiency virus. J Infect Dis. 2000 Sep;182(3):708-15. PMID: 10950763 Hu J, Gardner MB, Miller CJ. Simian immunodeficiency virus rapidly penetrates the cervicovaginal mucosa after intravaginal inoculation and infects intraepithelial dendritic cells. J Virol. 2000 Jul;74(13):6087-95. PMID: 10846092 Lu Y, Brosio P, Lafaile M, Li J, Collman RG, Sodroski J, Miller CJ. Vaginal transmission of chimeric simian/human immunodeficiency viruses in rhesus macaques. J Virol. 1996 May;70(5):3045-50. PMID: 8627782 Likewise it is evident that other lentiviruses can be transmitteed both sexually and through blood-blood contact: Jordan HL, Howard JG, Bucci JG, Butterworth JL, English R, Kennedy-Stoskopf S, Tompkins MB, Tompkins WA. Horizontal transmission of feline immunodeficiency virus with semen from seropositive cats. J Reprod Immunol. 1998 Dec;41(1-2):341-57. PMID: 1021332 Gradil CM, Watson RE, Renshaw RW, Gilbert RO, Dubovi EJ. Detection of bovine immunodeficiency virus DNA in the blood and semen of experimentally infected bulls. Vet Microbiol. 1999 Oct;70(1-2):21-31. PMID: 10591494 It should be noted though, that sexual transmission is not thought to be the predominant mode of transmission of some of the lentiviruses. For example, it is believed that equine infectious anemia virus can be transmitted by horseflies which carry significant amounts of blood from one horse to another. I have no doubt that David Rasnick can find excuses why none of those studies, nor any of the hundreds of other similar studies qualify as providing evidence that HIV-1 can be sexually transmitted in humans. So instead of having him waste his time making up those excuses, I would ask him to instead explain what sort of evidence there is that HIV-1 cannot possibly be sexually transmitted. He claims that the study by Nancy Padian et al. is "the best study" and that it provides compelling evidence that HIV-1 cannot possibly be sexually transmitted. The authors of that study claim that the 70 seroconversions which occurred prior to counseling on safer sex practices and no seroconversions after the participants were counseled, suggests that perhaps condoms are relatively effective at preventing sexual transmission of HIV-1. David Rasnick is correct to note that the size of the HIV-1 pandemic suggests that the sexual transmission of HIV-1 must be more efficient in unprotected heterosexual intercourse, than the Padian study found for condom-using couples. Although it is unethical to ask humans to have unprotected sex to directly test this hypothesis prospectively, retrospective analyses indeed indicate that HIV-1 transmission via unprotected heterosexual intercourse is indeed more than Padian et al. observed with condom-using couples. I already provided numerous examples, such as the Nushawn Williams case, where Nushawn was jailed in New York for infecting 13 of the 42 young women he slept with. Here are a few more, some of which suggest reasons why heterosexual transmission efficiency is observed to vary between groups. For example, open herpes simplex virus sores and other sources of blood-blood contact during sex are noted to vastly increase the transmission efficiency. Goudsmit J, Lukashov VV, van Ameijden EJ, Zorgdrager F, van den Burg R, Cornelissen M. Impact of sexual versus parenteral transmission events on the evolution of the gag and env genes of HIV type 1. AIDS Res Hum Retroviruses. 1998 Nov 1;14(16):1483-6. PMID: 9824326 Auvert B, Buve A, Ferry B, Carael M, Morison L, Lagarde E, Robinson NJ, Kahindo M, Chege J, Rutenberg N, Musonda R, Laourou M, Akam E. Ecological and individual level analysis of risk factors for HIV infection in four urban populations in sub-Saharan Africa with different levels of HIV infection. AIDS. 2001 Aug;15 Suppl 4:S15-30. PMID: 11686462 [No authors listed] Comparison of female to male and male to female transmission of HIV in 563 stable couples. European Study Group on Heterosexual Transmission of HIV. BMJ. 1992 Mar 28;304(6830):809-13. PMID: 1392708 Williams BG, Gouws E. The epidemiology of human immunodeficiency virus in South Africa. Philos Trans R Soc Lond B Biol Sci. 2001 Jul 29;356(1411):1077-86. PMID: 11516385 Henry K. Documented male-to-female transmission of HIV-1 after minimal vaginal exposure in the absence of other cofactors for infection. Minn Med. 1991 Oct;74(10):32-4. PMID: 1961169 Schacker T. The role of HSV in the transmission and progression of HIV. Herpes. 2001 Jul;8(2):46-9. Review. PMID: 11867018 Mabey D. Interactions between HIV infection and other sexually transmitted diseases. Trop Med Int Health. 2000 Jul;5(7):A32-6. PMID: 10964267 Mbopi-Keou FX, Gresenguet G, Mayaud P, Weiss HA, Gopal R, Matta M, Paul JL, Brown DW, Hayes RJ, Mabey DC, Belec L. Interactions between herpes simplex virus type 2 and human immunodeficiency virus type 1 infection in African women: opportunities for intervention. J Infect Dis. 2000 Oct;182(4):1090-6. PMID: 10979904 Padian NS, Shiboski SC, Jewell NP. Female-to-male transmission of human immunodeficiency virus. JAMA. 1991 Sep 25;266(12):1664-7. PMID: 1886189 O'Farrell N. Enhanced efficiency of female-to-male HIV transmission in core groups in developing countries: the need to target men. Sex Transm Dis. 2001 Feb;28(2):84-91. Review. PMID: 11234791 Mayer KH, Anderson DJ. Heterosexual HIV transmission. Infect Agents Dis. 1995 Dec;4(4):273-84. Review. PMID: 8665090 Korenromp EL, Bakker R, de Vlas SJ, Gray RH, Wawer MJ, Serwadda D, Sewankambo NK, Habbema JD. HIV dynamics and behaviour change as determinants of the impact of sexually transmitted disease treatment on HIV transmission in the context of the Rakai trial. AIDS. 2002 Nov 8;16(16):2209-18. PMID: 12409743 Auvert B, Buve A, Lagarde E, Kahindo M, Chege J, Rutenberg N, Musonda R, Laourou M, Akam E, Weiss HA. Male circumcision and HIV infection in four cities in sub-Saharan Africa. AIDS. 2001 Aug;15 Suppl 4:S31-40. PMID: 11686463 Birch CJ, McCaw RF, Bulach DM, Revill PA, Carter JT, Tomnay J, Hatch B, Middleton TV, Chibo D, Catton MG, Pankhurst JL, Breschkin AM, Locarnini SA, Bowden DS. Molecular analysis of human immunodeficiency virus strains associated with a case of criminal transmission of the virus. J Infect Dis. 2000 Sep;182(3):941-4. PMID: 10950794 <\PRE>
Competing interests: None declared

Potentially harmful letters should be peer reviewed 1 February 2003

Riccardo Baschetti,
retired medical inspector
CP 671, 60001-970 Fortaleza (CE), Brazil
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Re: Potentially harmful letters should be peer reviewed

Reason strongly suggests that the well-known, reported [1] case of the Haitian man who moved to Sweden and transmitted HIV to six sexual partners is more than sufficient to convince all sensible persons that HIV does spread by sexual contacts.
Although Rasnick's odd thesis that sex has nothing to do with AIDS [2, 3] is likely to be regarded by most readers as an innocuous nonsense, it nevertheless may produce tragic consequences, because it, having been published on the web site of the influential BMJ, can lead less scientifically educated people to abstain from using condoms, thereby jeopardising their health and favouring the spread of HIV.
It has rightly been stated that inaction towards HIV/AIDS is a crime against humanity "that cannot be tolerated any longer" [4]. Even more so, therefore, any interference with the prevention of HIV/AIDS should not be tolerated [5]. Rasnick's electronic letters, by implicitly claiming that no unprotected sexual intercourse can result in transmission of HIV, precisely constitute an intolerable and reckless interference with both the prevention of HIV/AIDS and the efforts of those who fight against the disease that is ravaging entire populations [4].
Since on our planet there are more than 6000 million different human brains, it is not surprising that some of them, as televised recently here in Brazil, still believe that the sun goes round the earth. Similarly, other funny ideas, such as the ones of Rasnick, should not be surprising. However, no one will be harmed by a television programme that could spread absurd astronomical views representing innocent fantasies, whereas the health of several individuals may be undermined by the publication of some eccentric claims on the web site of a leading medical journal. The BMJ, therefore, should use a peer review process to determine whether a potentially harmful submission deserves to be published or rejected.
1. Foley BT. HIV-1 and HIV-2 are sexually transmitted lentiviruses. <http://bmj.com/cgi/eletters/326/7381/126/e#29017>.
2. Rasnick D. Sex has nothing to do with AIDS. <http://bmj.com/cgi/eletters/326/7381/126/e#28943>.
3. Rasnick D. Still no sexual transmission of HIV, let alone AIDS. <http://bmj.com/cgi/eletters/326/7381/126/e#29276>.
4. Hogg R, Cahn P, Katabira ET, et al. Time to act: global apathy towards HIV/AIDS is a crime against humanity. Lancet 2002;360:1710-1.
5. Baschetti R. Interference with prevention of HIV/AIDS. Lancet 2003 (in press).
Competing interests: None declared

Baschetti wants to end debate 2 February 2003

David Rasnick,
Visiting Scientist Dept. MCB
UC Berkeley, Berkeley, CA 94720
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Re: Baschetti wants to end debate

Foley wants me to prove that HIV and AIDS are not sexually transmitted. The strongest evidence against the sexual transmission of HIV and AIDS is that after two decades there is no evidence for it. The $100 billion HIV/AIDS establishment (Johnson, J.A., AIDS funding for federal government programs: FY1981-FY2001. 2000, Congressional Research Service, The Library of Congress: Washington DC) has been telling the world for two decades that HIV and AIDS are sexually transmitted. But, astonishingly, the scientific evidence for that claim is at best difficult to find and probably doesn't exist. It is for Foley and other members of the mainstream to justify terrorizing hundreds of millions of people around the world by equating sex with death. The onus is no them to prove (or at least show that it is likely) that HIV and AIDS are sexually transmitted.
Foley says that, "David Rasnick is correct to note that the size of the HIV-1 pandemic suggests that the sexual transmission of HIV-1 must be more efficient in unprotected heterosexual intercourse, than the Padian study found for condom-using couples." Foley overlooks the fact that Padian et al. included non-condom-using couples in their study. Why didn't their non-condom-using couples transmit HIV?
Recently, Gisselquist et al. have documented that in serodiscordant couples in Africa the "rate of transmission [of antibodies to HIV] per coital act [is] only 0.0011, comparable to rates of 0.0003-0.0015 from similar studies in the US and Europe" (Gisselquist, D., et al., HIV infections in sub-Saharan Africa not explained by sexual or vertical transmission. Int J STD AIDS, 2002. 13: p. 657-666.). Gisselquist et al. point out that only 1.2% of African couples use condoms and yet they have the same low efficiency of transmitting antibodies to HIV as reported by Padian et al. Gisselquist et al. conclude that, "An expanding body of evidence challenges the conventional hypothesis that sexual transmission is responsible for more than 90% of adult HIV infections in Africa. Differences in epidemic trajectories across Africa do not correspond to differences in sexual behaviour. Studies among African couples find low rates of heterosexual transmission, as in developed countries."
Foley says that, "Although it is unethical to ask humans to have unprotected sex to directly test this hypothesis prospectively, retrospective analyses indeed indicate that HIV-1 transmission via unprotected heterosexual intercourse is indeed more than Padian et al. observed with condom-using couples." Is Foley's strongest evidence retrospective analyses? Remember, those retrospective analyses assumed from the start what needed to be demonstrated. That is, Padian et al. assumed (so does Foley) that the people who were HIV positive at the time they entered the study must have become positive through sexual intercourse prior to the study. Why does Foley give so much weight to the retrospective analyses (which represent a circular argument) and apparently discount the clear non-transmission of HIV between non-condom- using couples of the Padian et al. study? On what basis does Foley think scientists and doctors decided in 1980s to declare that HIV and AIDS were sexually transmitted? Surely, they didn't just pluck the sexual transmission of AIDS (or HIV for that matter) out of thin air--or did they?
Foley offers testimonials and a MEDLINE search of titles and abstracts to make his case. I counter with quotes from the body of the publications that contradict or refute the assertions and implications in the titles and abstracts that he offers as evidence. Relying so heavily on titles and abstracts, one would think that Foley considers the body of a scientific publication to be superfluous.
Joining the debate (or perhaps hoping to end it), Riccardo Baschetti says that, "Potentially harmful letters should be peer reviewed." (I guess that means my letters.) Potentially harmful to whom? Is Baschetti the judge of what is "Potentially harmful"? Is "peer reviewed" code for censored? To whom is it dangerous to investigate the evidence for and against the contagious/HIV hypothesis of AIDS?
A single "Haitian man who moved to Sweden and transmitted HIV to six sexual partners" is enough to convince Baschetti and "all sensible persons" that HIV is sexually transmitted. (I suppose those who disagree with Baschetti are not "sensible persons".) Such credulity in science and medicine is not only unprofessional it can lead to colossal blunders.
I'm often told there is overwhelming evidence to support the contagious/HIV hypothesis of AIDS but, curiously, the physicians and scientists making a comfortable living off the HIV gravy train are reluctant to provide even a sliver of that evidence when requested. One wonders why AIDS scientists and doctors are so reticent? It is only after being pushed into a corner that AIDS scientists and doctors bother to justify their views and opinions. The first course of action is often an appeal to authority. When that doesn�t work they resort to testimonials, MEDLINE searches of titles and abstracts but rarely, if ever, take the bull by the horns and really scrutinize the evidence to see if their beliefs are well-founded in science. In contrast with AIDS, scientists in other fields are usually all too eager to talk about their work, to dazzle colleagues with their brilliance, to convince them by attempting to show that all the evidence is consistent with and better explained by their theory, or that their approach is at least free from the paradoxes that plague competing theories. But with AIDS, discussion is dangerous and rarely tolerated. Again I ask, dangerous to whom?
If the evidence exists that HIV and AIDS are sexually transmitted, what harm does it do to go over it again, if for no other reason than to reassure everyone that the horses are hitched to the right buggy. The next time questions are raised about the sexual transmission of HIV and AIDS, Foley and Baschetti would be much better prepared to convince others of their assertions. But the complete lack of evidence for the contagious/HIV hypothesis of AIDS is turning it into the biggest scientific, medical blunder of the 20th century--perhaps of all time since it encompasses the globe.
Therefore, Brian Foley, aside from using titles of papers, what is the best scientific evidence that you know of that demonstrates (or "highly suggests") that HIV is sexually transmitted?
David Rasnick
Competing interests: None declared

An AIDS Ignorance Epidemic? 2 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: An AIDS Ignorance Epidemic?

With a total of 3.1 million deaths due to HIV/AIDS during 2002 alone, 610 000 of which were children under the age of 15 years(1), you would think that anyone trying to turn the last 15 years of AIDS research on its head by questioning the transmissibility of the disease would check their facts very, very closely wouldn't you?
Not the case here on the ol' BMJ. I've dredged up a copy of the American Journal of Epidemiology paper(2) that both Rasnick and Foley have discussed above to see which one of them is telling fibs. Padian et al state that:
Infectivity for HIV through heterosexual transmission is low, and STDs may be the most important cofactor for transmission.
It DOES NOT question the transmissibility of HIV, it just found a low heterosexual transmission rate in the study group used in Northern Carolina. I challenge anyone to get hold of the same paper - you will find that it in no way supports any crackpot theories about AIDS and sex.
For those interested in further reading an excellent summary can be found at: AIDS Denialists: How to Respond

References:
(1) http://www.unaids.org/
(2) Padian NS. Shiboski SC. Glass SO. Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology. 146(4):350-7, 1997 Aug 15.
(3) http://www.aids.org/immunet/atn.nsf/page/a-342-10"_top
Competing interests: � I am a Medical Student and have a habit of checking the facts.

Re: Baschetti wants to end debate 3 February 2003

Riccardo Baschetti,
retired medical inspector
CP 671, 60001-970 Fortaleza (CE), Brazil
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Re: Re: Baschetti wants to end debate

In my electronic response [1], I clearly pointed out that Rasnick's letters "can lead less scientifically educated people to abstain from using condoms, thereby jeopardising their health".
By asking "Potentially harmful to whom?" [2], Rasnick reveals either his intellectual dishonesty, or his inability to understand what he reads. In both cases, any further debate with him would represent a waste of time.
1. Baschetti R. Potentially harmful letters should be peer reviewed. <http://bmj.com/cgi/eletters/326/7381/126/e#29322>.
2. Rasnick D. Baschetti wants to end debate. <http://bmj.com/cgi/eletters/326/7381/126/e#29338>.
Competing interests: None declared

Rasnick can debate till the cows come home 3 February 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Rasnick can debate till the cows come home

> Foley wants me to prove that HIV and AIDS are not sexually transmitted.
There is no such thing as �proof� in regard to a topic such as this one. I am not asking David Rasnick to �prove� anything. I am only suggesting that if David Rasnick�s theory is that HIV cannot be transmitted by sexual contact, that he provide some evidence to support that theory.
> The strongest evidence against the sexual transmission of HIV and AIDS is that after two decades there is no evidence for it.
This is a blatant lie. There is a vast amount of evidence from many different fields of research, which all support the theory that HIV-1 and HIV-2 are lentiviruses which can be transmitted only by blood-blood or other close contact such as sexual contact, but not by casual contact such as sharing eating utensils, shaking hands, kissing, etc. The evidence that HIV-1 and HIV-2 can be transmitted by sexual contact is far more extensive than evidence that human influenza virus can be transmitted by sneezing, or that cholera can be transmitted through contaminated water.
>... justify terrorizing hundreds of millions of people around the world > by equating sex with death. The onus is no them to prove (or at least > show that it is likely) that HIV and AIDS are sexually transmitted.
Only an idiot would think that saying that HIV-1 is sexually transmitted is the same as �equating sex with death.� Just because the human influenza virus can be transmitted via aerosols does not mean that we all must stop breathing. Sex is not deadly. HIV-1 and HIV-2 are just two of the thousands of pathogens that humans face. They are transmitted sexually, but only from an infected person. Sex with an uninfected person is certainly not a risk.
Cholera can indeed be transmitted via water, but that does not mean that �drinking water is deadly�. It only means that people need to be aware of the methods available to ensure that the water they drink is not contaminated. One method is to test the water to make sure it is not contaminated. Another method is to filter the water through a filter with a pore size small enough to exclude Vibrio cholera. A third method is to use antimicrobial chemicals, ozone, radiation, or other methods to kill any Vibrio that might be in the water.
Indeed the onus is on the medical and epidemiological �establishments� to make sure that the public is truthfully informed about pathogens and other public health risks. The USA surgeon general requires that alcohol and tobacco products carry warning labels despite the fact than smoking a single pack of cigarettes is far less of a risk than having unprotected sex with an HIV-infected partner. There are certainly social and ethical considerations that would make it unthinkable to require warning labels to be put on HIV-infected people. But laws have been enacted in many states which require people who know that they are infected to warn their sexual partners.
>...Recently, Gisselquist et al. have documented that in serodiscordant couples in Africa the "rate of transmission [of antibodies to HIV] per coital act [is] only 0.0011, comparable to rates of 0.0003-0.0015 from similar studies in the US and Europe"
David Gisselquist did not do studies of serodiscordant couples, he only cited one or two other studies which did study couples. Also, he did not claim that HIV-1 could not be heterosexually transmitted at all. He only questioned whether or not nosocomial transmissions could account for 10% or more of all transmissions in sub-Saharan Africa.
>..."An expanding body of evidence challenges the conventional hypothesis that sexual transmission is responsible for more than 90% of adult HIV infections in Africa. Differences in epidemic trajectories across Africa do not correspond to differences in sexual behaviour. Studies among African couples find low rates of heterosexual transmission, as in developed countries."
This is correct. It is indeed possible that transmissions other than heterosexual transmissions account for more than 10% of all transmissions in sub-Saharan Africa. It is possible that homosexual acts have occurred in that region of the world. It is also possible that mother to infant transmission, IV drug user transmissions, and transmissions via tattoo equipment or other sources of blood-blood contact could have an impact on the epidemiology in sub-Saharan Africa. None of that would even slightly suggest that HIV-1 cannot be transmitted heterosexually.
> Foley says that, "Although it is unethical to ask humans to > have unprotected sex to directly test this hypothesis prospectively, > retrospective analyses indeed indicate that HIV-1 transmission via > unprotected heterosexual intercourse is indeed more than Padian > et al. observed with condom-using couples." Is Foley's strongest > evidence retrospective analyses?
No. Retrospective serosurveys are just one of dozens of methods for pinpointing the epidemilology of HIV-1 or any other pathogen. Contact tracing and other standard epidemiological methods also confirm that HIV-1 can be sexually transmitted. WIth the rapid evolution rate of HIV-1 and other retroviruses, a relatively new technique known as molecular epidemiology can also be used. David Rasnick simply ignores all published works on HIV-1 and simply says that nobody ever bothered to study how it was spread.
> Remember, those retrospective analyses assumed from the start what needed to be demonstrated.
This is another bold lie. Beginning in 1981, scientists and laymen have questioned every aspect of HIV and AIDS. Did it come from something in the �gay lifestyle�? Could it be something such as poppers? Could it be a certain food or vitamin? If it is a pathogen, how is it spread? If it is spread sexually, is it only via anal intercourse? Doe blood have to be exchanged? etc... Thousands of papers have been published, and David Rasnick would like to dismiss them all.
> On what basis does Foley think scientists and doctors decided in 1980s to declare that HIV and AIDS were sexually transmitted?
They first noted that it could be transmitted via blood-blood contact such as a transfusion from an AIDS patient (or future AIDS patient) into healthy people. They also noted that hemophiliacs became infected via the blood route. The homosexual community was very cooperative with contact tracing and other epidemiological surveys which established that unprotected anal intercourse was a route of transmission.
> Surely, they didn't just pluck the sexual transmission of AIDS (or HIV for that matter) out of thin air--or did they?
No. They did not. The book �And the Band Played On� by Randy Shilts is just one of dozens of books which chronicles the early epidemiological work.
> Foley offers testimonials and a MEDLINE search of titles and abstracts to make his case.
I cited just a few of the thousands of papers specifically address the subject at hand.
> I counter with quotes from the body of the publications that contradict or refute the assertions and implications in the titles and abstracts that he offers as evidence.
Nobody should ever take anyones word for anything. I am not citing the titles of papers but the full papers. If you want to read the digested version, pick up a review article or a textbook. The title, or one or two quotes taken from a paper can never tell the full story that the paper told. At a minimum, one must read the full abstract, but even the abstract can miss important details. If you take David Rasnick�s quotes as representative, you would think that Nancy Padian was convinced that HIV could not be transmitted heterosexually, and that David Gisselquist believed that nosocomial transmissions of HIV-1 accounted for more than 50% of the sub-Saharan epidemic.
> Relying so heavily on titles and abstracts, one would think that Foley considers the body of a scientific publication to be superfluous.
Quite the opposite! I refrain from posting the full abstracts here in the hope that people will be more likely to read the full papers.
> Riccardo Baschetti says that, "Potentially harmful letters should be peer reviewed." (I guess that means my letters.) Potentially harmful to whom?
To people who might be mislead into believing that HIV-1 cannot be sexually transmitted. Young sailors visiting Thailand in the mid to late 1980s for example. People also need to understand that HIV infection is not uniformly reportable to the CDC, only AIDS cases are. So the heterosexual epidemic in the USA is largely not yet reported because people infected today will not develop into AIDS cases for many more years. HIV infection in the USA is not just a problem for homosexuals and IV drug users.
> Is Baschetti the judge of what is "Potentially harmful"?
No. That should be left to courts and lawmakers to decide. It has become illegal to sell �snake oil� in the USA. It is still legal to sell lies about many things.
> Is "peer reviewed" code for censored?
Yes. It censors out many blatant lies, and provides a penalty system for fraud that slips through the system if it is caught later.
> To whom is it dangerous to investigate the evidence for and against the contagious/HIV hypothesis of AIDS?
Investigation is not dangerous at all. Failure to investigate is what is dangerous. What �investigations� have concluded that HIV-1 cannot be sexually tranmistted????
> A single "Haitian man who moved to Sweden and transmitted HIV to six sexual partners" is enough to convince Baschetti and "all sensible persons" that HIV is sexually transmitted. (I suppose those who disagree with Baschetti are not "sensible persons".) Such credulity in science and medicine is not only unprofessional it can lead to colossal blunders.
The story of the Haitian man in Sweden is not exceptional. There are tens of thousands of other such cases followed through �contact tracing�. The study done by Thomas Leitner et al was exceptional, in that it tested the limits of reliability of molecular epidemiology to reconstruct the epidemiology known through the contact tracing.
> I'm often told there is overwhelming evidence to support the contagious/HIV hypothesis of AIDS but, curiously, the physicians and scientists making a comfortable living off the HIV gravy train are reluctant to provide even a sliver of that evidence when requested.
If you have read the full text of all the papers I have cited and found them all to be completely unconvincing, why don�t you give us a sample critique of one or two of them???
> One wonders why AIDS scientists and doctors are so reticent?
One begins to understand the term �denialist�...
> If the evidence exists that HIV and AIDS are sexually transmitted, what harm does it do to go over it again, if for no other reason than to reassure everyone that the horses are hitched to the right buggy.
It has been gone over hundreds of time. Yet some denialists make false claims that it was never studied in the first place. Just because nobody has had an electron microscope in place inside a rectum or vagina at the very time of transmission, does not mean that there is no evidence at all that the virus can be transmitted sexually. Just because you deny that epidemiology and all other methods are invalid, does not mean that they are indeed invalid.
> But the complete lack of evidence for the contagious/HIV hypothesis of AIDS is turning it into the biggest scientific, medical blunder of the 20th century--perhaps of all time since It encompasses the globe.
If you truly have a valid argument about this, it is criminal not to make your case heard. So show us what you�ve got! Is Nancy Padian�s study your full �proof� that HIV-1 cannot be sexually transmitted? If 70 sexual transmissions is not enough, how many would you need?
> Therefore, Brian Foley, aside from using titles of papers,
Read the full papers. I am not going to violate copyright by posting the papers here. Talk to the authors of those papers. Talk to the surviving family members who knew the patients who died. Go do some real research and stop slinging clever but empty rhetoric in these meaningless e-letters. There are numerous lawsuits, such as the �Ricky Ray� class action suit, involving hundreds of millions of USA dollars. If you are jealous of the HIV/AIDS �gravy train� you must realize that there are even more dollars to be made in the opposing side. Smaller pond, but far fewer fish competing. For many scientists, money is not the motivator.
> what is the best scientific evidence that you know of that demonstrates (or "highly suggests") that HIV is sexually transmitted?
Conventional and molecular epidemiology.
The second best is "eyewitness" accounts. A significant percentage of HIV-infected people in the USA can tell you exactly who they caught the virus from. About 30 to 50% of the times that I catch a common cold, I can pinpoint my exposure to another person with a cold in the seven days prior to the onset of my symptoms. The symptoms of HIV infection take longer to develop, but most people have sex with fewer people than they shake hands with.

> David Rasnick > Competing interests: None declared
Competing interests: Getting very tired of this

Sex Without Condoms and Russian Roulette 3 February 2003

Tyrone Banks,
Lawyer
Sydney, 2000
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Re: Sex Without Condoms and Russian Roulette

Editor,
The responses to this article have gone from the sublime to the ridiculous.
Let's conduct an experiment to resolve the argument here and now. I'll find 10 women who agree to have no unsafe sex for 12 months, you provide 10 women who agree to have regular unsafe sex with HIV-positive male prostitutes for 12 months.
Then we'll get together in 1 year and again in 5 years to assess the health of both groups. Simple.
I'm not sure what is more ludicrous; the argument that AIDS isn't sexually transmitted, or the fact that such thoughts are given credibility by been hosted in an ostensibly credible Medical Journal?
Tyrone Banks
Competing interests: None declared

Quacks Don't Care for Facts - AIDS Ignorance Epidemic 4 February 2003

Tony Floyd,
Medical Student
Newcastle University, Australia 2308
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Re: Quacks Don't Care for Facts - AIDS Ignorance Epidemic

Brian Foley continues to counter Rasnick's specious argument with facts. I am sure he realises that such fanatics are unlikely to be swayed by logic. Perhaps he is hoping that BMJ readers will?
As I've already stated, sitting here with a copy of the Padian paper(1) that they have both referred to, it is hard to see it as anything but a nail in the coffin of those that would want us to doubt the fact that HIV is transmitted by (amongst other things) heterosexual sex.
I would probably infringe copyright by posting the paper here, so either:
1. Get hold of a copy from your local University library (if you're keen enough to see how fanatics twist the facts.)
or
2. Contact Nancy Padian herself and ask her what she has found. Otherwise go to either:

http://www.caps.ucsf.edu/capsweb/pe ople/padianbio.html
or
http://www. hsph.harvard.edu/hai/news_publications/tar/spring93/spring93-5.html
and read for yourself about her work.
You will find that her own bio states "In addition to continued study of the heterosexual transmission of HIV, her current research focuses on the efficacy of physical and barrier contraceptives that might decrease susceptibility to HIV and other STDS."
Keep quacking all you want, or stop and check the facts.
Tony Floyd

References:
(1) Padian NS. Shiboski SC. Glass SO. Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology. 146(4):350-7, 1997 Aug 15.

Competing interests: None declared

One more thing before we move on to the drugs 4 February 2003

David Rasnick,
Visiting Scientist Dept. MCB
UC Berkeley, Berkeley, CA 94720
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Re: One more thing before we move on to the drugs

Dear Editor,
Brian Foley says that the best evidence that HIV and AIDS are sexually transmitted is "Conventional and molecular epidemiology". Okay, what is the best published study (studies) that used "Conventional and molecular epidemiology" to demonstrate that HIV and AIDS are sexually transmitted? I will, as Foley asked, lay my hands on that paper (papers) and provide a critique.
Foley says that the second best evidence is "eyewitness" accounts. The Padian et al. 1997 study was an attempt to provide exactly that: eyewitness accounts of sexual transmission of HIV. As the authors state several times in that paper they did not observe even one HIV negative sex partner become HIV positive during the entire 10 years of the study. Thus, no eyewitness account of sexual transmission in a study designed to observe it. So, I would like to know just where an eyewitness study as good as or better than the Padian el al. study is published.
After Foley posts the references to the studies that used "conventional and molecular epidemiology" to demonstrate that HIV and AIDS are sexually transmitted, we can move on to examine the anti-HIV drug issue that he raised earlier. What is the evidence that the anti-HIV drugs do more good than harm?
David Rasnick
Competing interests: None declared

Re: One more thing before we move on to the drugs 5 February 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Re: One more thing before we move on to the drugs

David Rasnick wrote: "Brian Foley says that the best evidence that HIV and AIDS are sexually transmitted is "Conventional and molecular epidemiology". Okay, what is the best published study (studies) that used "Conventional and molecular epidemiology" to demonstrate that HIV and AIDS are sexually transmitted? I will, as Foley asked, lay my hands on that paper (papers) and provide a critique. " I have already listed numerous studies in prior corresponence, but I will provide some more here. I truly cannot think of any one study that I think is "the best". In fact, I would never trust any one study or group or related studies by the same authors. The trustworthyness of most scientific data lies in the reproducibility of results found by different groups. In the papers below I have followed just a couple of these lines of evidence, primarily the concordance between viral load observed in the "donor" and risk of seroconversion in the "recipient" in both homosexual and heterosexual transmission of HIV-1 in various cohorts that have been studied. In a prior letter above, I provided references showing that infection with herpes simplex virus of the donor and/or recipient were noted increase the risk of heterosexual transmission of HIV-1. I do not expcet David Rasnick to have time to critiques each of These studies independently. Most of them use the same methods and similar cohorts of individuals. I am quite interested in hearing how he will use these studies to prove that HIV-1 cannot possibly be sexually transmitted. Tovanabutra S, Robison V, Wongtrakul J, Sennum S, Suriyanon V, Kingkeow D, Kawichai S, Tanan P, Duerr A, Nelson KE. Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand. J Acquir Immune Defic Syndr. 2002 Mar 1;29(3):275-83. PMID: 11873077 Fideli US, Allen SA, Musonda R, Trask S, Hahn BH, Weiss H, Mulenga J, Kasolo F, Vermund SH, Aldrovandi GM. Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa. AIDS Res Hum Retroviruses. 2001 Jul 1;17(10):901-10. PMID: 11461676 Ragni MV, Faruki H, Kingsley LA. Heterosexual HIV-1 transmission and viral load in hemophilic patients. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Jan 1;17(1):42-5. PMID: 9436757 Pedraza MA, del Romero J, Roldan F, Garcia S, Ayerbe MC, Noriega AR, Alcami J. Heterosexual transmission of HIV-1 is associated with high plasma viral load levels and a positive viral isolation in the infected partner. J Acquir Immune Defic Syndr. 1999 Jun 1;21(2):120-5. PMID: 10360803 Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, Meehan MO, Lutalo T, Gray RH. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000 Mar 30;342(13):921-9. PMID: 10738050 Hisada M, O'Brien TR, Rosenberg PS, Goedert JJ. Virus load and risk of heterosexual transmission of human immunodeficiency virus and hepatitis C virus by men with hemophilia. The Multicenter Hemophilia Cohort Study. J Infect Dis. 2000 Apr;181(4):1475-8. PMID: 10753732 Gray RH, Wawer MJ, Brookmeyer R, Sewankambo NK, Serwadda D, Wabwire-Mangen F, Lutalo T, Li X, vanCott T, Quinn TC. Probability of HIV-1 transmission per coital act in monogamous, heterosexual, HIV-1-discordant couples in Rakai, Uganda. Lancet. 2001 Apr 14;357(9263):1149-53. PMID: 11323041 Laga M, Taelman H, Van der Stuyft P, Bonneux L, Vercauteren G, Piot P. Advanced immunodeficiency as a risk factor for heterosexual transmission of HIV. AIDS. 1989 Jun;3(6):361-6. PMID: 2568844 Hsieh YH, de Arazoza H, Lee SM, Chen CW. Estimating the number of Cubans infected sexually by human immunodeficiency virus using contact tracing data. Int J Epidemiol. 2002 Jun;31(3):679-83. PMID: 12055173 Ramstedt K, Hallhagen G, Lundin BI, Hakansson C, Johannisson G, Lowhagen GB, Norkrans G, Giesecke J. Contact tracing for human immunodeficiency virus (HIV) infection. Sex Transm Dis. 1990 Jan-Mar;17(1):37-41. PMID: 2305335 Deschamps MM, Pape JW, Hafner A, Johnson WD Jr. Heterosexual transmission of HIV in Haiti. Ann Intern Med. 1996 Aug 15;125(4):324-30. PMID: 8678397 Guimaraes MD, Munoz A, Boschi-Pinto C, Castilho EA. HIV infection among female partners of seropositive men in Brazil. Rio de Janeiro Heterosexual Study Group. Am J Epidemiol. 1995 Sep 1;142(5):538-47. PMID: 7677133 Seidlin M, Vogler M, Lee E, Lee YS, Dubin N. Heterosexual transmission of HIV in a cohort of couples in New York City. AIDS. 1993 Sep;7(9):1247-54. PMID: 8216983 Fiore JR, Zhang YJ, Bjorndal A, Di Stefano M, Angarano G, Pastore G, Fenyo EM. Biological correlates of HIV-1 heterosexual transmission. AIDS. 1997 Jul 15;11(9):1089-94. PMID: 9233454 Karon JM, Rosenberg PS, McQuillan G, Khare M, Gwinn M, Petersen LR. Prevalence of HIV infection in the United States, 1984 to 1992. JAMA. 1996 Jul 10;276(2):126-31. PMID: 8656504 Downs AM, De Vincenzi I. Probability of heterosexual transmission of HIV: relationship to the number of unprotected sexual contacts. European Study Group in Heterosexual Transmission of HIV. J Acquir Immune Defic Syndr Hum Retrovirol. 1996 Apr 1;11(4):388-95. PMID: 8601226 Leynaert B, Downs AM, de Vincenzi I. Heterosexual transmission of human immunodeficiency virus: variability of infectivity throughout the course of infection. European Study Group on Heterosexual Transmission of HIV. Am J Epidemiol. 1998 Jul 1;148(1):88-96. PMID: 9663408 DeGruttola V, Seage GR 3rd, Mayer KH, Horsburgh CR Jr. Infectiousness of HIV between male homosexual partners. J Clin Epidemiol. 1989;42(9):849-56. PMID: 2789269 de Vincenzi I. A longitudinal study of human immunodeficiency virus transmission by heterosexual partners. European Study Group on Heterosexual Transmission of HIV. N Engl J Med. 1994 Aug 11;331(6):341-6. PMID: 8028613 Louria DB, Skurnick JH, Palumbo P, Bogden JD, Rohowsky-Kochan C, Denny TN, Kennedy CA. HIV heterosexual transmission: a hypothesis about an additional potential determinant. Int J Infect Dis. 2000;4(2):110-6. PMID: 10737850 Johnson AM, Petherick A, Davidson SJ, Brettle R, Hooker M, Howard L, McLean KA, Osborne LE, Robertson R, Sonnex C, et al. Transmission of HIV to heterosexual partners of infected men and women. AIDS. 1989 Jun;3(6):367-72. PMID: 2502150 David goes on to state: " Foley says that the second best evidence is "eyewitness" accounts. The Padian et al. 1997 study was an attempt to provide exactly that: eyewitness accounts of sexual transmission of HIV. As the authors state several times in that paper they did not observe even one HIV negative sex partner become HIV positive during the entire 10 years of the study." Now David Rasnick is again repeating the same blatant lie that was already pointed out previously. There were 70 seroconversions during the ten year period. The direct observation of the patients after safer-sex counselling did not cover the full ten years, the patients were counselled at different times, such that the longest period followed was six years. There were no seroconversions observed after the patients were counselled to engage only in safe sex (although they did not all follow this advice 100% of the time), and the authors concluded that condom usage, even if there was less than 100% adherance, greatly reduced the risk of heterosexual transmission.

Competing interests: None declared

Eyewitness accounts 6 February 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Eyewitness accounts

David Rasnick mistook my statement about "Eyewitness accounts" to include such things as Nancy Padian's paper. I did NOT mean researcher's reports like that. What I meant was actually talking to HIV-infected people at the local AIDS clinic and asking them if they know how they contracted the virus, and if so, what makes them sure that they know.
If David Rasnick does not want to actually interview some HIV- infected people, he could at least do a http://www.google.com/ search for "contracted HIV personal story" and he would find one hundred or so stories told in the first person.
There are surely a few people who have had so many random sexual encounters that they do not know who infected them or when. But a significant number of people know exactly who infected them and when it happened. This is what makes "contact tracing" an effective tool for limitting the spread of HIV-1, syphillis, tuberculosis, and many other pathogens.
I did the GOOGLE search, and here are a few samples:
www.avert.org/womstory.htm www.avert.org/manstory.htm www.hivaids.webcentral.com.au/text/st048.html www.dailyfreepress.com/news/357355.html mindprod.com/hiv.html www.hivaids.webcentral.com.au/text/st005.html www.exodusnorthamerica.org/resources/section.cfm?sid=4
David Rasnick claims he can make AIDS go away just by "re-thinking" it. We all wish that were true. But sometimes research as well are rethinking, is needed.
Competing interests: None declared

Foley's references, stay tuned 6 February 2003

David Rasnick,
Visiting Scientist, Dept. MCB
UC Berkeley, Berkeley, CA 94720
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Re: Foley's references, stay tuned

Dear Editor,
Brian Foley provides a formidable list of 21 (if I counted right) references that he feels contains the best evidence that HIV is sexually transmitted. He lists two references from 2002, two from 2001, three from 2000, one from 1999, two from 1998, one from 1997, three from 1996, one from 1995, one from 1994, one from 1993, one from 1990, and three from 1989, if I added them up right.
The first thing that strikes me about this list is its length. Watson and Crick�s Nobel-prize-wining paper describing the structure of DNA took no more than two pages. Second, and of no less importance, is that almost all of the citations are to recent publications. One wonders if this list of references (or a subset) is what has convinced most researchers that HIV is sexually transmitted. If it is, they had to wait a long time for that evidence. I will bet Brian Foley the beverage of this choice that those studies he cites assume from the start that HIV is sexually transmitted and were not designed to actually put that assumption to the test. It is important to remember that scientists and doctors working in the 1980s would not have had the benefit of Foley's references as a basis for deciding whether or not HIV was indeed sexually transmitted. Yet they did come to that conclusion.
Therefore, to live up to my end of the bargain I will lay my hands on Foley's earliest references, the three 1989 papers and the single 1990 paper, read them and report back as to what evidence they provide towards answering the question: Is HIV sexually transmitted? Who knows, they may actually contain the evidence I'm asking for. We shall see. Stay tuned.
David Rasnick
Competing interests: None declared

HIV: a marker of barrier disruptions and personal hygiene? 6 February 2003

Richard G Fiddian-Green,
None
None
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Re: HIV: a marker of barrier disruptions and personal hygiene?

To what extent might HIV positivity be a marker of cervical epithelial barrier disruption and personal hygiene?
1. There is an association between HIV and other sexually transmitted diseases.
2. In Southern Africa access to clean water and the privacy for personal hygiene with any regularity is limited or non-existant in rural areas, many being forced to wash in exposed and surprisingly small streams that are also being used to obtain drinking water and to wash clothes.
3. Access to and the money available to buy sanitary products may be limited or non-existent in rural communities.
4. Prostitutes in Kenya might be less likely to contract HIV because of their living in the more affluent urban districts, the superior income they might generate, and their commerical need for constant cleanliness.
The co-existence of recurrent episodes of gut mucosal barrier disruption, which is also very common in rural populations, might be another cause for HIV positivity. It might even increase the risk of contracting HIV by compromising gut associated lymphoid tissue functions and by permitting the translocation of gut toxins and associated release of cytokines which might also induce or compound the severity of any immunological deficiency.
Competing interests: � None declared

Re: Foley's references, stay tuned 7 February 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Re: Foley's references, stay tuned

David Rasnick writes: > The first thing that strikes me about this list is its length. David is now using the debating technique of "moving the goalposts". He ignored my request for Evidence of any sort that hints that HIV-1 cannot be sexually transmitted, and asked for me to provide the "best " evidence that HIV-1 can be sexually transmitted. I replied that no one study is clearly "best" and provided a sampling of recent studies that I thought were very good because they were by different research groups from different countries, which all agreed on various points. For example, numerous studies have shown that co-infection with herpes simplex virus influences the risk of transmission of HIV-1 per sexual enounter, as does viral load of HIV-1 in the donor partner. Now David is claiming that he wants the "earliest" evidence, rather than the "best": > Second, and of no less importance, is that almost all of the citations are to > recent publications. One wonders if this list of references (or a subset) is > what has convinced most researchers that HIV is sexually transmitted. Certainly NOT. Gay related immune deficiency, was re-named "AQUIRED" immune deficiency syndrome (AIDS) rather early in the studies of the epidemiology of this syndrome. Here are a few of the early publications: JAMA 1983 Sep 9;250(10):1310-2 Acquired immune deficiency syndrome in low-risk patients. Evidence for possible transmission by an asymptomatic carrier. Pitchenik AE, Fischl MA, Spira TJ. Two patients who contracted acquired immune deficiency syndrome (AIDS) could not be included in any of the known high-risk groups for this syndrome (ie, they were not homosexual, intravenous [IV] drug abusers, Haitian, or hemophiliacs). Patient 1, however, had regular sexual contact with her husband, an IV drug abuser who is asymptomatic despite a severe T-cell defect (T-helper cells, 33/cu mm; T-helper/T-suppressor ratio, 0.32; and a depressed lymphoproliferative response to mitogens and antigens). We hypothesize that he may be an asymptomatic carrier of an AIDS agent that he transmitted to his wife through intimate heterosexual contact. This mode of sexual transmission may provide a vector for the spread of AIDS to low-risk populations. PMID: 6224028 Biggar RJ, Melbye M, Ebbesen P, Andersen HK, Vestergaard BF. [The immune suppression syndrome in homosexual men. An epidemiological study from the Cancer Research Institute in Arhus] Ugeskr Laeger. 1982 Mar 15;144(11):777-80. Danish. PMID: 7101504 Ann Intern Med 1982 Oct;97(4):533-9 Opportunistic infection in previously healthy women. Initial manifestations of a community-acquired cellular immunodeficiency. Masur H, Michelis MA, Wormser GP, Lewin S, Gold J, Tapper ML, Giron J, Lerner CW, Armstrong D, Setia U, Sender JA, Siebken RS, Nicholas P, Arlen Z, Maayan S, Ernst JA, Siegal FP, Cunningham-Rundles S. Opportunistic infections and unusual tumors have been reported in an unprecedented outbreak of community-acquired cellular immune deficiency among homosexual and drug-abusing men. We report five women with the same syndrome. The women were residents of metropolitan New York City closely associated with drug abuse either by personal use (our patients) or close sexual contact with an abuser (one patient). One patient was bisexual. All five patients developed Pneumocystis carinii pneumonia as well as combinations of other opportunistic infections including oral candida, disseminated mycobacteria, and ulcerative herpes simplex infections. All patients had marked depression of cellular immune function. Three patients died. The appearance of this syndrome in women has important implications with regard to the epidemiology and etiology of this emerging syndrome. PMID: 6982014 Goudsmit J, Wertheim-van Dillen P, Schellekens PT, Coutinho RA, Danner SA, van der Noordaa J. Acquired immune deficiency syndrome, altered T cell subset ratios, and cytomegalovirus infections among male homosexuals in The Netherlands. Antibiot Chemother. 1983;32:138-46. PMID: 6087724 N Engl J Med 1981 Dec 10;305(24):1425-31 Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, Wolf RA, Saxon A. Four previously healthy homosexual men contracted Pneumocystis carinii pneumonia, extensive mucosal candidiasis, and multiple viral infections. In three of the patients these infections followed prolonged fevers of unknown origin. In all four cytomegalovirus was recovered from secretions. Kaposi's sarcoma developed in one patient eight months after he presented with esophageal candidiasis. All patients were anergic and lymphopenic; they had no lymphocyte proliferative responses to soluble antigens, and their responses to phytohemagglutinin were markedly reduced. Monoclonal-antibody analysis of peripheral-blood T-cell subpopulations revealed virtual elimination of the Leu-3 / helper/inducer subset, an increased percentage of the Leu-2 + suppressor/cytoxic subset, and an increased percentage of cells bearing the thymocyte-associated antigen T10. The inversion of the T/ helper to suppressor/cytotoxic ratio suggested that cytomegalovirus infection was an important factor in the pathogenesis of the immunodeficient state. A high level of exposure of male homosexuals to cytomegalovirus-infected secretions may account for the occurrence of this immune deficiency. PMID: 6272109 MMWR Morb Mortal Wkly Rep 1983 Jan 7;31(52):697-8 Immunodeficiency among female sexual partners of males with acquired immune deficiency syndrome (AIDS) - New York. PMID: 6402650 Can Med Assoc J 1983 Dec 1;129(11):1205-9 Opportunistic infections and acquired cellular immune deficiency among Haitian immigrants in Montreal. LeBlanc RP, Simard M, Flegel KM, Gilmore NJ. Eight Haitian immigrants (five with acquired immune deficiency syndrome [AIDS] and three with the signs and symptoms of AIDS but without opportunistic infections or malignant diseases) are described. All had malaise, weight loss, fever and generalized lymphadenopathy. All five of those with opportunistic infections died from the infections, which were multiple in four cases. Septic shock due to Escherichia coli or Klebsiella pneumoniae developed in two patients. Evidence of immune deficiency in the AIDS patients included anergy, lymphocytopenia (in all but two), polyclonal hypergamma-globulinemia and abnormal sizes of the subsets of circulating T lymphocytes. Autopsies revealed no recognizable causes for immune deficiency; the lymph nodes showed follicular hyperplasia in four cases and lymphocyte depletion in one case. Except for the absence of opportunistic infections, the illness in the three patients not classed as having AIDS was indistinguishable from that in the other five, which suggests that this syndrome is AIDS-related, like the persistent generalized lymphadenopathy that occurs in homosexual men and patients with hemophilia. PMID: 6315211 Levine AS. The epidemic of acquired immune dysfunction in homosexual men and its sequelae--opportunistic infections, Kaposi's sarcoma, and other malignancies: an update and interpretation. Cancer Treat Rep. 1982 Jun;66(6):1391-5. PMID: 6282458 Proc Natl Acad Sci U S A 1983 Aug;80(16):5085-9 Transmission of naturally occurring lymphoma in macaque monkeys. Hunt RD, Blake BJ, Chalifoux LV, Sehgal PK, King NW, Letvin NL. Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and cryptosporidiosis. They also showed evidence of an abnormal circulating peripheral blood mononuclear cell. These findings, all characteristic of the acquired immune deficiency syndrome (AIDS) of macaques, suggest a link between these transmissible lymphomas and AIDS in macaque monkeys. PMID: 6576377 > If it is, they had to wait a long time for that evidence. I will bet Brian Foley the beverage > of this choice that those studies he cites assume from the start that HIV is sexually > transmitted and were not designed to actually put that assumption to the test. I would not be surprised if studies designed to determine exactly what factors influence the transmissibility of HIV-1 during heterosexual intercourse (factors such as viral load in the donor) conducted in the late 1990s to early 2000s did not feel a need to build into the design of the experiment a test to see if HIV-1 can indeed be sexually transmitted at all. When NASA sends a shuttle into orbit they don't re-test the theory of gravity or the sherical shape of the earth, they take htose factors as already well established. I have previously stated that studies which encourage humans to become HIV-infected are Unethical and illegal. Can David Rasnick be specific about what type of evidence would be required to satisfy him? If so, can he cite similar studies that have been carried out for any other pathogen? It may not be ethical by many people's standards, but primates have been used to directly test the transmissibility of SIVs. I already provided references, and David had no comment on them. > It is important to remember that scientists and doctors working in the 1980s would > not have had the benefit of Foley's references as a basis for deciding whether or not HIV > was indeed sexually transmitted. Yet they did come to that conclusion. Yes. They noted first, through contact tracing and other forms of conventional epideimiolgy, that many of the early homosexual AIDS cases were linked by direct sexual contact, or at least had sexual partners in common. More importantly, blood and other tissue samples from many of the early GRID or AIDS cases have been frozen away frozen away, and although molecular epidemiological techniques were not possible prior to characterization of the HIV-1 viruses in the mid 1980s to mid 1990s, these early tissues samples can now be analysed to confirm the sexual transmission that (as David says) was suspected but not "proven" by conventional epidemiology alone. One such case was the study done by Thomas Leitner, which investigated the molecular epidemiology of HIV-1 subtype B transmission from a Hatian man to several women in Sweden: Proc Natl Acad Sci U S A 1996 Oct 1;93(20):10864-9 Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis. Leitner T, Escanilla D, Franzen C, Uhlen M, Albert J. Department of Clinical Virology, Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, Sweden. Phylogenetic analyses are increasingly used in attempts to clarify transmission patterns of human immunodeficiency virus type 1 (HIV-1), but there is a continuing discussion about their validity because convergent evolution and transmission of minor HIV variants may obscure epidemiological patterns. Here we have studied a unique HIV-1 transmission cluster consisting of nine infected individuals, for whom the time and direction of each virus transmission was exactly known. Most of the transmissions occurred between 1981 and 1983, and a total of 13 blood samples were obtained approximately 2-12 years later. The p17 gag and env V3 regions of the HIV-1 genome were directly sequenced from uncultured lymphocytes. A true phylogenetic tree was constructed based on the knowledge about when the transmissions had occurred and when the samples were obtained. This complex, known HIV-1 transmission history was compared with reconstructed molecular trees, which were calculated from the DNA sequences by several commonly used phylogenetic inference methods [Fitch-Margoliash, neighbor-joining, minimum- evolution, maximum-likelihood, maximum-parsimony, unweighted pair group method using arithmetic averages (UPGMA), and a Fitch-Margoliash method assuming a molecular clock (KITSCH)]. A majority of the reconstructed trees were good estimates of the true phylogeny; 12 of 13 taxa were correctly positioned in the most accurate trees. The choice of gene fragment was found to be more important than the choice of phylogenetic method and substitution model. However, methods that are sensitive to unequal rates of change performed more poorly (such as UPGMA and KITSCH, which assume a constant molecular clock). The rapidly evolving V3 fragment gave better reconstructions than p17, but a combined data set of both p17 and V3 performed best. The accuracy of the phylogenetic methods justifies their use in HIV-1 research and argues against convergent evolution and selective transmission of certain virus variants. PMID: 8855273 > Therefore, to live up to my end of the bargain I will lay my hands on Foley's > earliest references, the three 1989 papers and the single 1990 paper, read them > and report back as to what evidence they provide towards answering the question: > Is HIV sexually transmitted? Again, David uses the debate technique known as "argument from authority". He does not encourage the readers of this debate to check my references themselves, he states that he is the "expert" and you should trust his interpretation of what those papers contain. Given his track record for interpretting other papers, I would instead encourage anyone who is interested in HIV transmission to read the papers themselves. If anyone feels that the "medical establishment" cannot be trusted, then no research paper will every be convincing, and I would encourage you to visit the local AIDS clinic and talk to AIDS patients directly.

Competing interests: None declared

Re: HIV: a marker of barrier disruptions and personal hygiene? 7 February 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Re: HIV: a marker of barrier disruptions and personal hygiene?

Richard Fiddian-Green wrote: > 1. There is an association between HIV and other sexually transmitted diseases. Not much of one. A few infections that cause open sores, such as herpes simplex virus, have been shown to increase the sexual transmission rate of HIV-1, but there is really no "association" between HIV and other STDs that would not be expected to exist between any two STDs. Sure, people who have sex are more likely to have an STD than virgins. > 2. In Southern Africa access to clean water and the privacy for personal hygiene > with any regularity is limited or non-existant in rural areas, many being forced to > wash in exposed and surprisingly small streams that are also being used to obtain > drinking water and to wash clothes. HIV infections in southern Africa do not tend to correte very well with access to clean water. A recent comprehensive study of HIV-1 infections in South Africa can be found here: http://www.hsrc.ac.za/research/npa/SAHA/news/20021205Main.html or http://www.hsrcpublishers.co.za/e-library/HIV/ The Nelson Mandela/HSRC report states "There was no significant different in the HIV prevalence among those who reported that they were working (14.2%) and those who reported that they were not working (12.1%) (P=0.7)." "�there is a decrease in HIV prevalence from the poorer to richer homes when all participants are included. � However, this trend disappears when only Africans are consideres, as in this group there is no discernable trend." > 3. Access to and the money available to buy sanitary products may be > limited or non-existent in rural communities. Actually, rural Africans have a much lower HIV seroprevalence rate than urban. In many parts of Africa, people living rural traditional lives are not at high risk of HIV infection. Rom J Virol 1998 Jan-Dec;49(1-4):89-95 Human immunodeficiency virus types 1 and 2 infection in some rural areas of Nigeria. Odaibo GN, Olaleye OD, Tomori O. Department of Virology, College of Medicine, University College Hospital, Ibadan, Nigeria. The prevalence of human immunodeficiency virus types 1 and 2 in rural areas of Nigeria was estimated using 1089 sera collected in 18 locations from 1992 to early 1994. The sera were tested with Enzyme linked Immunosorbent Assay (ELISA) and confirmed by Western Immunoblotting technique. Overall, 13 (1.2%) of the 1089 sera were positive for antibodies to HIV-1 and HIV-2. Prevalence of 0.6% and 0.8% were obtained for HIV-1 and HIV-2 respectively. The highest prevalence of HIV-1 and HIV-2 (50.0%) were found in Zuhlrrua and Umubuzu. A seroprevalence of 1.2% was obtained for both male and female groups tested. The highest prevalence of HIV was found among individuals 30-39 years age group. An overall increase in prevalence of HIV-1 and HIV-2 infection was obtained over the three years during which samples were collected for this study (0.7% in 1992, 1.0% in 1992 and 3.4% in 1994). In addition, two sera were positive for both HIV-1 and HIV-2. The detection of antibodies to HIV-1 and HIV-2 in the rural areas where blood samples were collected for this study shows that both viruses are widespread in the rural communities of Nigeria. PMID: 10892430 Trop Doct 1999 Apr;29(2):94-8 HIV and syphilis serostatus of antenatals in traditional Maasai pasturalist communities in Kajiado District, Kenya: 1989-1992. Valadez JJ, Loolpapit PM, Nyangao A, Dikir F. Department of International Health, Johns Hopkins University School of Hygiene and Public Health, Baltimore, USA. josephvaladez@compuserve.com Although much research has been carried out on high risk populations, little is known about HIV prevalence in traditional rural communities who limit contact with other tribes, non-traditional tribesman and Europeans. This study considers traditional Maasai living near a high HIV transmission area. A time series analysis assessed the trend of HIV-1 and syphilis prevalences in the study area. Data consist of antenatal blood specimens (n = 2082 women) collected during 1989-1992. An estimated 100% of pregnant women residing in the study areas are included in the study. Standardized HIV-1 prevalences among women for 1989-1992 ranged between 0.95% and 2.23%. A chi 2 test for trends was not significant, analysis of age-specific prevalences revealed no significant result. Standardized syphilis prevalence varied from 1.89% to 12.82% during the 3 years. Prevalence declined in 1990, but increased significantly thereafter. A steep 1992 increase in syphilis was not associated with an increase in HIV. Chi square test for trends for age-specific syphilis was not significant. In 2082 samples only one woman was positive for both HIV and syphilis. In 4 years no increase in HIV prevalence was detected among traditional Maasai woman living near a high transmission area. No significant variation across ages was detected. However, syphilis increased sharply in one time period, 1992. Despite the low HIV prevalence among Maasai, the higher prevalence of syphilis suggests that the HIV epidemic is at an early phase and may increase soon. It may also suggest that HIV does not yet have a high prevalence at markets where Maasai sell their herds, but is concentrated at truck stops. PMID: 10418300 > 4. Prostitutes in Kenya might be less likely to contract HIV because of their > living in the more affluent urban districts, the superior income they might > generate, and their commerical need for constant cleanliness. WHAT??? Less likely to contract HIV than who? Prostitutes in Kenya and many other places where HIV is prevalent are highly likely to contract HIV. I suspect that you are being confused by a study of the rare, and therefor very interesting case of a minority of the commercial sex workers in Nairobi who were found to be exposed to HIV yet remained seronegative: J Infect 1996 Jul;33(1):33-7Bacteriuria in a cohort of predominantly HIV-1 seropositive female commercial sex workers in Nairobi, Kenya. Ojoo J, Paul J, Batchelor B, Amir M, Kimari J, Mwachari C, Bwayo J, Plummer F, Gachihi G, Waiyaki P, Gilks C. Kenya Medical Research Institute, Nairobi, Kenya. Although significant bacteriuria and urinary tract infection are more common in immunocompetent women than men, studies linking HIV immunosuppression with an increased risk of developing urinary infection have so far only been carried out in men. We therefore examined the relationship between bacteriuria and HIV status and CD4+cell count in a relatively homogeneous cohort of female commercial sex workers (CSW) attending a community clinic in Nairobi. Two hundred and twenty-two women were enrolled, and grouped according to HIV status and CD4 count. Group 1 were HIV seronegative (n = 52); Group 2 were HIV seropositive with CD4 + counts above 500 x 10(6)/l (n = 51); Group 3 were HIV seropositive with CD4 + counts between 201 and 500 x 10(6)/l (n = 67); Group 4 were HIV seropositive with CD4+counts below 200 x 10(6)/l (n = 52). Clinical signs and symptoms were noted and mid-stream specimens of urine obtained for culture and sensitivity. Overall 23% (50/222) had significant bacteriuria. The rates in each group respectively were 25%, 29%, 19% and 23% and there was no significant association between bacteriuria and HIV status; or between bacteriuria and level of immuno-suppression as indicated by CD4 + count. Overall 19% (30/222) of women had symptoms (frequency; dysuria; loin pain; smelly urine) or signs (fever; loin tenderness) compatible with urinary tract infection. However there was no significant association between symptoms or signs of infection and bacteriuria or HIV status. A typical range of pathogens, predominantly Enterobacteriaceae, were isolated and there were high rates of resistance to commonly used antimicrobials as well as 10% resistance to ciprofloxacin. Although high rates of significant bacteriuria can occur in highly sexually-active women, this appears unrelated to HIV infection or the level of HIV-related immunosuppression and is generally asymptomatic or clinically indistinct. PMID: 8842992 Lancet 1996 Nov 16;348(9038):1347-51 Resistance to HIV-1 infection among persistently seronegative prostitutes in Nairobi, Kenya. Fowke KR, Nagelkerke NJ, Kimani J, Simonsen JN, Anzala AO, Bwayo JJ, MacDonald KS, Ngugi EN, Plummer FA. Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada. BACKGROUND: There is indirect evidence that HIV-1 exposure does not inevitably lead to persistent infection. Heterogeneity in susceptibility to infection could be due to protective immunity. The objective of this study was to find out whether in highly HIV-1-exposed populations some individuals are resistant to infection. METHODS: We did an observational cohort study of incident HIV-1 infection- among 424 initially HIV-1-seronegative prostitutes in Nairobi, Kenya, between 1985 and 1994. 239 women seroconverted to HIV-1 during the study period. Exponential, Weibull, and mixture survival models were used to examine the effect of the duration of follow-up on incidence of HIV-1 infection. The influence of the duration of exposure to HIV-1 through prostitution on seroconversion risk was examined by Cox proportional hazards modelling, with control for other known or suspected risk factors for incident HIV-1 infection. HIV-1 PCR with env, nef, and vif gene primers was done on 43 persistently seronegative prostitutes who remained seronegative after 3 or more years of follow-up. FINDINGS: Modelling of the time to HIV-1 seroconversion showed that the incidence of HIV-1 seroconversion decreased with increasing duration of exposure, which indicates that there is heterogeneity in HIV-1 susceptibility or acquired immunity to HIV-1. Each weighted year of exposure through prostitution resulted in a 1.2-fold reduction in HIV-1 seroconversion risk (hazard ratio 0.83 [95% CI 0.79-0.88], p < 0.0001). Analyses of epidemiological and laboratory data, show that persistent seronegativity is not explained by seronegative HIV-1 infection or by differences in risk factors for HIV-1 infection such as safer sexual behaviours or the incidence of other sexually transmitted infections. Interpretation: We conclude that a small proportion of highly exposed individuals, who may have natural protective immunity to HIV-1, are resistant to HIV-1. PMID: 8918278

Competing interests: None declared

Wrong Question ? 7 February 2003

James E Parker,
Retired Paediatrician
289 McCallum Rd , Abbotsford BC CANADA V2S 8A1
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Re: Wrong Question ?

WhileDr Rasnick's logic - 'sex has nothing to do with AIDS' may be as congruent as stating sex has nothing to do with pregnancy, his right to debate, however outrageous,brings forth valuable discussion and has served as a foil to Brian Foley's cogent responses. Truth becomes an early victim when rebuttal cannot be entertained in the forum of debate.
Controversy regarding the infectivity of retroviruses is not new. Feline leukaemia virus discovered in 1964 (Jarrett WFH et al( Nature (lond) 1964 202 : 566) was still considered by some not to be horizontally transmitted ten years later ( Schneider R J Am Vet Med Assoc 1974 164 :1070). A test and removal program with controls by Hardy and associates (Hardy WD, McLelland AJ et al Nature 1976 263 : 326) of cats in infected households effectively resolved this dilemma. Indeed a vaccine has subsequently been developed for cat leukaemia. A test and removal program in HIV /AIDS is not considered feasible or ethical although experience in Cuba should be noted.
In Foley's response of Feb 1st( 're still no sexual transmission of HIV let alone AIDS ') he mentions "It should be noted though that sexual transmission is not thought to be the predominant mode of transmission of some of the lentiviruses. for example it is believed that equine infectious anaemia virus can be transmitted by horseflys".
We know that HIV can be sexually transmitted (whatever Dr Rasnick's opinion) the important question however is can it also be transmitted extra sexually ?
James E Parker
Competing interests: None declared

Prelude to critique 8 February 2003

David Rasnick,
Visiting Scientist, Dept. MCB
UC Berkeley, Berkeley, CA 94720
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Re: Prelude to critique

It is interesting that Brian Foley accuses me of "argument from authority". He is the one flooding the readers with Medline search results in the place of argument and skeptical analysis. He seems to be counting on the shear tonnage of the close to 200,000 publications produced from the $100 billion of HIV funding over the past two decades to win the day. He accuses me of "not encourag[ing] the readers of this debate to check [our] references themselves". Where did I ever say that? Foley says that I claim to be "the 'expert' and you should trust [my] interpretation of what those papers contain." Where did I ever say that? I am the one who is encouraging skepticism and debate. I am certainly not trying to discourage it. Foley claims that I said that I "can make AIDS go away just by 're- thinking' it." Where did I ever say that? If Foley is going to quote me he better get the quotes right and reference them.
As promised, I have studied the four earliest of the 21 papers that Brian Foley offers as the best evidence that HIV is sexually transmitted. But, before scrutinizing these papers, it will be helpful to examine a fallacy in his argument concerning the Padian et al. 1997 study. He says that, "there were 70 [HIV] seroconversions during the ten year period" of the the study. Not true. Those 70 people where antibody positive to HIV at the time they entered the Padian et al. study. They did not become antibody positive after entering the study. There is no way of knowing from the Padian et al. study when or how those 70 people became antibody positive to HIV. Even had they been observed to go from antibody negative to positive during the study, that still does not mean that it was because of sex. It would have been suggestive of sexual transmission but it is certainly a long way from proof. I will use a parable to illustrate the fallacy in Foley's logic, which out of necessity is shared by those hoping to get NIH funding to do HIV research.
Suppose that in all of the references that Foley cites as evidence that HIV is sexually transmitted we were talking about diabetes instead of AIDS or HIV. Everywhere you see HIV, AIDS or infection you replace them with the word diabetes or diabetic. Since Foley is fond of abstracts, we will use the abstract of the Padian et al study as an example of the fallacy in logic. This little story will also make clear the explicit assumption of sexual transmission.
Padian, N.S., et al., Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten- year study. Am J Epidemiol, 1997. 146(4): p. 350-7.
Altered abstract To examine rates of and risk factors for heterosexual transmission of diabetes, the authors conducted a prospective study of diabetic individuals and their heterosexual partners who have been recruited since 1985. Participants were recruited from health care providers, research studies, and health departments throughout Northern California, and they were interviewed and examined at various study clinic sites. A total of 82 diabetic women and their male partners and 360 diabetic men and their female partners were enrolled. Over 90% of the couples were monogamous for the year prior to entry into the study; < 3% had a current sexually transmitted disease (STD). The median age of participants was 34 years, and the majority were white. Over 3,000 couple-months of data were available for the follow-up study. Overall, 68 (19%) of the 360 female partners of diabetic men (95% confidence interval (CI) 15.0-23.3%) and two (2.4%) of the 82 male partners of diabetic women (95% CI 0.3-8.5%) were diabetic. History of sexually transmitted diseases was most strongly associated with transmission. Male-to-female transmission was approximately eight-times more efficient than female-to-male transmission and male-to-female per contact infectivity was estimated to be 0.0009 (95% CI 0.0005-0.001). Over time, the authors observed increased condom use (p < 0.001) and no new diabetes. Infectivity for diabetes through heterosexual transmission is low, and STDs may be the most important cofactor for transmission. Significant behavior change over time in serodiscordant couples was observed.
This fanciful study would make sense only if it had already been proved beyond doubt that diabetes was sexually transmitted. However, the protocol of the Padian et al. study was not designed to prove the sexual transmission of anything, including HIV, and it certainly did not provide evidence to justify the sexual transmission of HIV (diabetes).
A critique of the four references suggested by Foley will follow.
David Rasnick
Competing interests: None declared

Evidence against sexual transmission of HIV and AIDS. 9 February 2003

David Rasnick,
Visiting Scientist, Dept. MCB
UC Berkeley, Berkeley, CA 94720
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Re: Evidence against sexual transmission of HIV and AIDS.

Foley has asked that I provide evidence against the sexual transmission of HIV. The early mainstream AIDS literature itself provides a great deal of data that raise serious doubts about HIV and AIDS being sexually transmitted.
If either HIV or AIDS were sexually transmitted then the quantitative evidence for sexual transmission should readily be found studying prostitutes. However, there is ample evidence that prostitution is not, in and of itself, a risk factor for AIDS. In fact, sex with a prostitute is not even listed as a risk category by the American CDC, and the following evidence explains why.
Seidlin et al. examined the prevalence of antibodies to HIV in New York City call girls during 1987 (Seidlin, M., et al., Prevalence of HIV infection in New York call girls. J Acquir Immune Defic Syndr, 1988. 1(2): p. 150-4). They studied 78 women who had been prostitutes for an average of over 5 years. Each woman had had an average of over 200 clients during the past year, or approximately 1,000 lifetime partners. Use of condoms was sporadic at best. Vaginal intercourse was common, while anal intercourse was rare. Despite all this sexual activity (which certainly would be a risk factor for acquiring and transmitting a sexually transmissible disease) and despite living in one of the AIDS capitals of the world, only one of the women was HIV-positive. And, she admitted to being an iv drug user. Her 72 non-drug using co-workers were all HIV- negative.
Another study carried out in New York City between 1982 and 1988 found similar results. Joyce Wallace et al. surveyed several hundred streetwalkers for a variety of measures of immunodeficiency (Wallace, J., Case presentation of AIDS in the United States, in AIDS and Infections of Homosexual Men, P. Ma and D. Armstrong, Editors. 1989, Butterworths: Boston. p. 285-295). Excluding admitted iv drug users from their study (the women were not tested for drug use), they found that only 4.5 percent of the prostitutes were HIV-positive. The only statistically significant difference between the HIV-positive and negative women was that the former had had a mean of 3,062 sex partners during their lifetimes, whereas the negatives had had 1,047.
Another US study in 1988 found similar results. The authors concluded that, "HIV infection in non-drug using prostitutes tends to be low or absent, implying that sexual activity alone does not place them at high risk, while prostitutes who use intravenous drugs are far more likely to be infected with HIV" (Rosenberg, M.J. and J.M. Weiner, Prostitutes and AIDS: A health department priority? Am. J. Public Health, 1988. 78: p. 418-423).
The same results were reported from Amsterdam, one of the world's centers of legalized prostitution. When several hundred non-drug using prostitutes were studied, investigators found no HIV-positive women even though they averaged more than 200 clients per year (Coutinho, R.A. and T. van der Helm, [No indications for LAV/HTLV-III in non-drug-using prostitutes in Amsterdam]. Ned Tijdschr Geneeskd, 1986. 130(11): p. 508).
The story repeats itself for prostitutes in Germany, Zurich, Vienna, London, Paris, Pardenone (Italy), and Athens. (Klinische Wochenschrift 65: 287 (1987), Luthy et al.; Wiener Klinische Wochenschrift 98: 697 (1986), Kopp & Dangl-Erlach; Lancet ii: 1424 (1985), Brenky-Fandeux & Fribourg-Blanc; British Medical Journal 297: 1585 (1988), Day et al.; Scand J Infect Dis 21: 353 (1988), Hyams et al.)
Below are the points I made in a previous letter.
None of the husbands of HIV positive women became antibody positive to HIV over a three-year period. (Lancet ii: 581 (1985), Stewart et al.}
No transmission of HIV was observed between couples in which all of the women were HIV positive and in which at least 100 sexual contacts occurred. (JAMA 259: 3037 (1988), Padian et al.)
After a mean of 3-1/2 years of unprotected intercourse, with an average of 50 sexual encounters per year, only one hemophiliac wife became HIV positive. (American Journal of Medicine 85: 472 (1988), Kim et al.)
No transmission of T-cell abnormalities from hemophiliacs with AIDS to their spouses. (JAMA 251: 1450 (1984), Kreiss et al.)
"The number of American and European heterosexuals who have had sexual relations with a prostitute, who have no other admitted risk factors (such as drug abuse), and who have subsequently developed antibody to HIV can be counted on the fingers of one hand" (Rethinking AIDS, Root- Bernstein (1993).
The implications of these and related studies are astounding. HIV cannot be a sexually transmitted disease, in the usual sense. The same studies cited above demonstrated that most prostitutes, regardless of whether they are drug users and regardless of whether they regularly use condoms with their clients, eventually develop the standard sexually transmitted diseases of syphilis, gonorrhea, and herpes. But, with only a handful of exceptions, only drug-using prostitutes contract antibodies to HIV. The US National Academy of Sciences even admits as much in their 1990 report, "AIDS: The Second Decade", when they state that non-drug using prostitutes have no higher risk of AIDS than other women.
One clear implication of these studies is that non-drug using heterosexuals should have little risk of HIV or AIDS. Indeed, testing the prevalence of antibodies to HIV among new recruits by the US Army, the US Navy, and the Marine Corps (groups succeptible to sexually transmitted diseases) (Burke, D.S., et al., Human immunodeficiency virus infections in teenagers; seroprevalence among applicants for the U.S. military service. J. Am. Med. Assoc., 1990. 263(15): p. 2074-2077; Garland, F.C., et al., Incidence of human immunodeficiency virus seroconversion in US Navy and Marine Corps personnel, 1986 through 1988. Jama, 1989. 262(22): p. 3161- 5), and among first-time blood donors of all ages by the Red Cross (Centers for Disease Control, Summary of Surveillance Data. 1989, Centers for Disease Control: Atlanta. p. 36-38) has been carried out since 1985, when the Abbott HIV antibody test became available. All three sets of data demonstrate clearly that the prevalence of antibodies to HIV in the general population was no more common in 1992 than in 1985. The same general trends have been observed in Canada and Britain as well. AIDS and people with antibodies to HIV are staying within the same risk groups first identified in the early 1980s: gay men, drug addicts, hemophiliacs (about one percent), and blood transfusion recipients (about one percent).
After evaluating the evidence, Robert Root-Bernstein concludes that, "in Europe and the Americas, the transmission of HIV through heterosexual intercourse is so rare that two heterosexuals without identified risks for AIDS have an equal probability of being struck by lightening, dying in a commercial airplane crash, or developing AIDS" (Root-Bernstein, R., Rethinking AIDS: The tragic cost of premature consensus. 1993, New York, NY: Free Press).
So, given all this evidence against sexual transmission of HIV and AIDS, I think it is fair to ask what is the best evidence that either HIV or AIDS or both are sexually transmitted?
David Rasnick
Competing interests: None declared

Promised critique of Foley�s references 9 February 2003

David Rasnick,
Visiting Scientist, Dept. MCB
UC Berkeley, Berkeley, CA 94720
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Re: Promised critique of Foley�s references

Here is my promised critique of the four earliest of the 21 papers that Brian Foley offers as the best evidence that HIV is sexually transmitted. I will abbreviate each paper by the first letter of the author's last name as shown below.
(D) DeGruttola, V., et al., Infectiousness of HIV between male homosexual partners. J Clin Epidemiol, 1989. 42(9): p. 849-56.
(L) Laga, M., et al., Advanced immunodeficiency as a risk factor for heterosexual transmission of HIV. Aids, 1989. 3(6): p. 361-6.
(J) Johnson, A.M., et al., Transmission of HIV to heterosexual partners of infected men and women. Aids, 1989. 3(6): p. 367-72.
(R) Ramstedt, K., et al., Contact tracing for human immunodeficiency virus (HIV) infection. Sex Transm Dis, 1990. 17(1): p. 37-41.
As expected, all four of these papers assumes from the start that HIV is sexually transmitted. None of the papers was designed to test that hypothesis. See a previous letter titled "Prelude to Foley's references" for a criticism of this assumption that is shared by Foley.
Here is how I summarize Foley's argument. I hope he will correct any errors I may have made interpreting his position. Foley claims that the sex partners of the HIV-positive "index" cases who were HIV-positive themselves at the time of enrollment into the Padian et al. sexual transmission study published in 1997 are proof that those HIV-positive sex partners must have become HIV-positive from sex with the index cases sometime before entering the study. Padian et al. explicitly state that, "transmission occurred prior to entry in the study" (Padian, N.S., et al., Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. Am J Epidemiol, 1997. 146(4): p. 350-7). It cannot be stated enough that during the entire length of the Padian et al. study, which lasted 10 years, the authors did not observe even a single HIV-negative partner become HIV-positive.
Now to the four references. Reference (R) is of little import to the question of proof. The paper describes a method for contact tracing of people who came in contact with HIV positive persons. This paper does not bear on whether or not HIV or AIDS is sexually transmitted. One could just as well perform contact tracing of people who come in contact with diabetics, which would also produce a tracing diagram of those contacts who turned out to be diabetic themselves, and the much larger number of contacts who are not diabetic. Such a bizarre undertaking would only make sense if diabetes were contagious. I will have nothing further to say about this paper unless Foley or others wish to talk about it.
There is a common problem acknowledged in the remaining three references, and indeed recognized in the publications on sexual transmission throughout the second half of the 1980s up to the present. I will quote from the three papers to set the stage.
From (D): "some men with large numbers of receptive anal sexual contacts remain uninfected while others with infrequent contact become infected."
From (L): "The lack of association between HIV infection in the contacts and the number of sexual encounters was unexpected. ...Thus, some partners became infected after only a few sexual encounters, while others remained uninfected despite frequent unprotected sexual intercourse for several years after infection of the index case."
From (J): "In common with a number of studies, no relationship was found between transmission probability and either length of relationship or estimated number of sexual contacts."
The lack of correlation between the number of sexual contacts with HIV-positive partners and risk of becoming HIV-positive was also disclosed in a 1988 CDC study, which found that, "although most husbands and wives remained uninfected despite repeated sexual contact without protection, some acquired infection after only a few contacts" (Peterman, T.A., et al., Risk of human immunodeficiency virus transmission from heterosexual adults with transfusion-associated infections. JAMA, 1988. 259: p. 55-58).
There is another very serious discrepancy, which is the profound differences in sexual transmission in the USA and Europe compared to Africa. As Nancy Padian and John Pickering pointed out in 1986, "The ratio of male-to-female AIDS cases varies geographically. In the United States, this ratio has been 13:1 since the beginning of the epidemic. In Africa, the ratio is closer to unity..." (Padian, N. and J. Pickering, Female-to- male transmission of AIDS: a reexamination of the African sex ratio of cases. Jama, 1986. 256(5): p. 590). The authors go on to say that, "The low African sex ratio does not necessarily confirm that AIDS in Africa is predominantly transmitted by heterosexual contact. ...While it is true that in Africa, the incidence of AIDS and infection with HTLV- III/lymphadenopathy-associated virus/AIDS-related virus is nearly equal among [sic] men and women, we ought not automatically to assume that heterosexual transmission of the AIDS virus is likely here [in the USA]".
That is an amazing statement when you think about it, because it is just exactly what a scientist should have assumed about a supposedly sexually transmitted disease. Aside from AIDS, what other sexually transmitted disease targets men and women so completely differently depending on where they live?
It is impossible for Padian et al. and the rest of mainstream AIDS researchers to honestly face the paradoxes that they themselves had discovered about the hypothesis that HIV and AIDS are sexually transmitted. Since they are not allowed to question any of the axioms of AIDS, mainstream researchers are forced to come up with bizarre ad hoc arguments to explain why AIDS is so completely different from all other contagious and sexually transmitted diseases.
Just as with the Padian et al. study, the HIV-positive sex partners of the index cases were positive at entry in (D), (L) and (J). However, (J) was different in that, �Seronegative contacts were interviewed and re- tested [for antibodies to HIV] when possible at six monthly intervals, although in many cases sexual relationships ended.� As with many other studies, �Seropositives and seronegatives did not differ in terms of frequency of protected or unprotected vaginal intercourse� (J). There is a tidbit of interesting information that the authors of (J) provided in passing. �Two seropositive contacts reported only one act of sexual intercourse with their seropositive partner. In both cases, seroconversion was documented. Details of these two cases are provided in the Appendix.� Amazingly, the appendix does not provide any source information or other documentation of these �documented� seroconversions. We just have to take their word for it.
There are numerous other problems with these papers, but I think I have made the point that they fall seriously short of proving that HIV is sexually transmitted. Naturally, Foley and others are free to dispute my conclusion by raising other points in the papers. I will be happy to address their specific criticisms and arguments.
However, it appears from this analysis that the sexual transmission of AIDS and HIV is an example of what Irving Langmuir, Nobel prize winner in chemistry, calls pathological science. Here are Langmuir's Rules of Pathological Science along with corresponding examples from the AIDS literature.
1) The maximum effect that is observed is produced by a causative agent of barely detectable intensity, and the magnitude of the effect is substantially independent of the intensity of the cause.
(The levels of HIV in a person are so small that instead of looking for the virus directly, antibodies against it are needed to label a person HIV-positive. From 30 to 45 cycles of PCR are typically used to detect otherwise invisible quantities of viral fragments. As we have seen, the likelihood of becoming HIV antibody positive from sex is independent of the number of sexual contacts.)
2) The effect is of a magnitude that remains close to the limit of delectability or, many measurements are necessary because of the very low statistical significance of the results.
(Padian et al. did not observe even a single sex partner going from HIV-negative to HIV-positive during a ten year study that could have seen it. Non-drug using female prostitutes have the same probability of becoming HIV-positive as women in general.)
3) There are claims of great accuracy.
(The AIDS literature is replete with claims of great accuracy.)
4) Fantastic theories contrary to experience are suggested.
(Ad hoc explanations are proposed to reconcile the colossal differences between AIDS in Africa and the developed world. David Ho et al. speculated that HIV is killing billions of T-cells every day but the body replaces them to maintain a steady state for 10 years until, magically, the immune system poops out (Ho, D.D., et al., Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature, 1995. 373(6510): p. 123-6). To resolve the paradox of the cytopathic HIV that isn't, AIDS researchers now investigate 16 hypothetical and unconfirmed mechanisms of cytopathogenicity (McCune J M The dynamics of CD4+ T-cell depletion in HIV disease; Nature 2001. 410: p. 974-9).
5) Criticisms are met by ad hoc excuses thought up on the spur of the moment. (Inspect the letters responding to my criticisms of the sexual transmission of HIV and AIDS.)
6) The ratio of supporters to critics rises up to somewhere near 50% and then falls gradually to oblivion.
Langmuir's last point is clearly wrong when it comes to AIDS. He hadn't counted on $100 billion of taxpayer life support to keep the contagious/HIV hypothesis of AIDS from a quick demise.
David Rasnick
Competing interests: None declared

Re: Foley and barrier integrity 10 February 2003

Richard G Fiddian-Green,
None
None
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Re: Re: Foley and barrier integrity

Foley's response has not addressed my suggestion that HIV positivity might be a marker of barrier disruption rather than a STD. What, for example, does elimination of intestinal parasites and avoidance of recurrent bouts of dysentery do to HIV positivity? Might not outcome be far more effectively and cost-effectively improved by eliminating gut pathologies that by addressing STD and HIV positivity?
Competing interests: None declared

AIDS Denial May be an Excuse for Not Wearing Condoms 13 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: AIDS Denial May be an Excuse for Not Wearing Condoms

A study of over a thousand Isreali adolescents found HIV/AIDS-related denial to be a factor in infrequent condom use(1). Surely attempts to question the transmissibility of AIDS via heterosexual intercourse will do nothing but give young people another reason to NOT wear condoms???
The MMWR report mentioned by one of the papers above(2) is available on line at http://www.cdc.gov/mmwr/PDF/wk/mm4820.pdf. Sexual transmission was linked by DNA analysis to a male who had infected 10 of the 42 females who had slept with him with HIV. I wonder what these 10 women would make of the AIDS-Denialist debate?
Other interesting reading may be found at:
The Evidence That HIV Causes AIDS
HIV, AIDS, and the Distortion of Science

References:
(1) Ben-Zur H. Breznitz S. Wardi N. Berzon Y. Denial of HIV/AIDS and preventive behaviour among Israeli adolescents. Journal of Adolescence. 23(2):157-74, 2000 Apr.
(2) Cluster of HIV-Positive Young Women. MMWR 1999;48:413-416

Competing interests: None declared

Apparently, debate and condoms are not compatible 14 February 2003

David Rasnick,
Visiting Scientist, Dept. MCB
UC Berkeley, Berkeley, CA 94720
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Re: Apparently, debate and condoms are not compatible

According to Tony Floyd, we should not debate the contagious/HIV hypothesis of AIDS in this professional medical journal because of the droves of young people breathlessly taking in every word, looking for any excuse to stop using condoms. Floyd cites a CDC Morbidity and Mortality Weekly Report (MMWR) to support his dire warning. Since the authors did not attempt to determine whether or not HIV and AIDS are in fact sexually transmitted, for the purposes of this debate, I will say nothing more about the MMWR.
Floyd cites an anonymous, unpublished article that purportedly gives "The Evidence That HIV Causes AIDS". The article, which was spared the scrutiny of peer review, appears on the NIAID (part of the NIH) website:
http://www.niaid.nih.gov/factsheets/evidhiv.htm
Since the authors have not attached their names to the article, we don't know who takes responsibility for the assertions made in it, nor do we know to whom we should direct questions and criticisms. The NIAID's anonymous, unpublished article was intended to end the persistent questions and criticisms of the contagious/HIV hypothesis of AIDS. The NIAID article provides mainstream doctors and scientists with a facile means of deflecting embarrassing questions about the growing number of paradoxes and outright contradictions of the contagious/HIV hypothesis of AIDS. The NIAID article is invoked to preempt debates before they get started.
Floyd also uses an unusual source in support of his position. He cites an article from the non-scientific literature titled "HIV, AIDS, and the Distortion of Science", May 2000, written by former marketing and public relations consultants Martin Delaney, now director of Project Inform. Project Inform is a non-governmental, San Francisco-based disseminator of mainstream AIDS information and an advocacy arm for the NIH and pharmaceutical companies that make billions of dollars from AIDS. This is interesting because Martin Delaney used to be one of the angriest critics of AZT. In the 1980s, Delaney took advantage of the Freedom of Information Act to obtain FDA documents on the approval of AZT. Here is how he summarized what he found.
"The multi-center clinical trials of AZT are perhaps the sloppiest and most poorly controlled trials ever to serve as the basis for an FDA drug licensing approval... Because mortality was not an intended endpoint, causes of death were never verified. Despite this, and a frightening record of toxicity, the FDA approved AZT in record time, granting a treatment IND [investigational new drug] in less than five days and full pharmaceutical licensing in less than 6 months" (Lauritsen, J., Poison by Prescription-The AZT Story. 1990, New York: Asklepios Press, page 26-27)
But, considerable financial aid from pharmaceutical companies (Lauritsen, J., The AIDS War: propaganda, profiteering and genocide from medical-industrial complex. 1993, New York: Asklepios, pages 438-440) and personal consultations with Anthony Fauci, director of the NIAID, transformed Delaney from being one of the most vocal critics of AZT into a staunch advocate of the drug and the other antiretrovirals (Duesberg, P.H., Inventing the AIDS Virus. 1996, Washington: Regnery Publishing Inc., page 378).
David Rasnick
Competing interests: � None declared

Re: Evidence against sexual transmission of HIV and AIDS. 15 February 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Re: Evidence against sexual transmission of HIV and AIDS.

David Rasnick wrote: > Foley has asked that I provide evidence against the sexual transmission > of HIV. The early mainstream AIDS literature itself provides a great > deal of data that raise serious doubts about HIV and AIDS being sexually > transmitted. If either HIV or AIDS were sexually transmitted then the > quantitative evidence for sexual transmission should readily be found > studying prostitutes. However, there is ample evidence that prostitution > is not, in and of itself, a risk factor for AIDS. In fact, sex with a > prostitute is not even listed as a risk category by the American CDC, > and the following evidence explains why. We were actually discussing sexual transmission of HIV-1 and not specifically heterosexual transmission. There is however ample evidence of heterosexual transmission of HIV-1 in prostitutes at later time points in the USA epidemic, as well as at many time points in epidemics in other countries. Sex does not cause AIDS, nor does sex cause a false-positive HIV-1 ELISA. Unprotected sexual intercourse (whether homosexual or heterosexual) with an HIV-infected person does put one at risk of contracting the virus from the previously infected person. David Rasnick presents a few papers from the early USA and European epidemics showing that HIV-1 infections were not very common among female heterosexual prostitutes. This is equivalent to presenting data from a few prisons in the USA showing no tuberculosis infections and concluding from that data that tuberculosis cannot be spread by coughing in a prison. It is not sex that causes AIDS, and it is not coughing that causes tuberculosis. It is infection with a pathogen that causes the syndrome or disease, and the pathogen can be spread by sex or coughing ONLY if the pathogen is present. > Seidlin et al. examined the prevalence of antibodies to HIV in New > York City call girls during 1987 (Seidlin, M., et al., Prevalence of > HIV infection in New York call girls. J Acquir Immune Defic Syndr, > 1988. 1(2): p. 150-4). They studied 78 women who had been prostitutes > for an average of over 5 years. Each woman had had an average of > over 200 clients during the past year, or approximately 1,000 lifetime > partners. Use of condoms was sporadic at best. Vaginal intercourse > was common, while anal intercourse was rare. Despite all this sexual > activity (which certainly would be a risk factor for acquiring and > transmitting a sexually transmissible disease) and despite living in > one of the AIDS capitals of the world, only one of the women was > HIV-positive. And, she admitted to being an iv drug user. Her 72 > non-drug using co-workers were all HIV- negative. HIV-1 seroprevalence among New York heterosexuals was low in the 1984-1990 time period. Sampling just 78 people from that pool would not necessarily be expected to turn up many cases of infection. > Another study carried out in New York City between 1982 and 1988 > found similar results. Joyce Wallace et al. surveyed several hundred > streetwalkers for a variety of measures of immunodeficiency > (Wallace, J., Case presentation of AIDS in the United States, in AIDS > and Infections of Homosexual Men, P. Ma and D. Armstrong, Editors. > 1989, Butterworths: Boston. p. 285-295). Excluding admitted iv drug > users from their study (the women were not tested for drug use), they > found that only 4.5 percent of the prostitutes were HIV-positive. The > only statistically significant difference between the HIV-positive and > negative women was that the former had had a mean of 3,062 sex > partners during their lifetimes, whereas the negatives had had 1,047. While David may feel that "only 4.5% infection" is so low that it proves that HIV-1 cannot be sexually transmitted, I do not believe that interpretation. > So, given all this evidence against sexual transmission of HIV > and AIDS, I think it is fair to ask what is the best evidence that > either HIV or AIDS or both are sexually transmitted? There has always been epidemiological evidence such as: Glauser MP, Francioli P. Clinical and epidemiological survey of acquired immune deficiency syndrome in Europe. Eur J Clin Microbiol. 1984 Feb;3(1):55-8. PMID: 6705776 Redfield RR, Markham PD, Salahuddin SZ, Sarngadharan MG, Bodner AJ, Folks TM, Ballou WR, Wright DC, Gallo RC. Frequent transmission of HTLV-III among spouses of patients with AIDS-related complex and AIDS. JAMA. 1985 Mar 15;253(11):1571-3. PMID: 2983127 Redfield RR, Markham PD, Salahuddin SZ, Wright DC, Sarngadharan MG, Gallo RC. Heterosexually acquired HTLV-III/LAV disease (AIDS-related complex and AIDS). Epidemiologic evidence for female-to-male transmission. JAMA. 1985 Oct 18;254(15):2094-6. PMID: 2995695 Kreiss JK, Kitchen LW, Prince HE, Kasper CK, Essex M. Antibody to human T-lymphotropic virus type III in wives of hemophiliacs. Evidence for heterosexual transmission. Ann Intern Med. 1985 May;102(5):623-6. PMID: 2984972 Jason JM, McDougal JS, Dixon G, Lawrence DN, Kennedy MS, Hilgartner M, Aledort L, Evatt BL. HTLV-III/LAV antibody and immune status of household contacts and sexual partners of persons with hemophilia. JAMA. 1986 Jan 10;255(2):212-5. PMID: 3001375 Fischl MA, Dickinson GM, Scott GB, Klimas N, Fletcher MA, Parks W. Evaluation of heterosexual partners, children, and household contacts of adults with AIDS. JAMA. 1987 Feb 6;257(5):640-4. PMID: 3467077 Clumeck N, Robert-Guroff M, Van de Perre P, Jennings A, Sibomana J, Demol P, Cran S, Gallo RC. Seroepidemiological studies of HTLV-III antibody prevalence among selected groups of heterosexual Africans. JAMA. 1985 Nov 8;254(18):2599-602. PMID: 2997491 And the more recent molecular epidemiological studies have solidly proven that HIV-1 and HIV-2 are sexually transmitted both by heterosexual contacts and homosexual contacts: Trask SA, Derdeyn CA, Fideli U, Chen Y, Meleth S, Kasolo F, Musonda R, Hunter E, Gao F, Allen S, Hahn BH. Molecular epidemiology of human immunodeficiency virus type 1 transmission in a heterosexual cohort of discordant couples in Zambia. J Virol. 2002 Jan;76(1):397-405. PMID: 11739704 Gao F, Robertson DL, Carruthers CD, Li Y, Bailes E, Kostrikis LG, Salminen MO, Bibollet-Ruche F, Peeters M, Ho DD, Shaw GM, Sharp PM, Hahn BH. An isolate of human immunodeficiency virus type 1 originally classified as subtype I represents a complex mosaic comprising three different group M subtypes (A, G, and I). J Virol. 1998 Dec;72(12):10234-41. PMID: 9811767 Kane CT, Montavon C, Toure MA, Faye MA, Ndiaye AG, Diallo AG, Ndoye I, Liegeois F, Delaporte E, Mboup S, Peeters M. Full-length genome sequencing of HIV type 1 group O viruses isolated from a heterosexual transmission cluster in Senegal. AIDS Res Hum Retroviruses. 2001 Aug 10;17(12):1211-6. PMID: 11522190 Leitner T, Escanilla D, Franzen C, Uhlen M, Albert J. Accurate reconstruction of a known HIV-1 transmission history by phylogenetic tree analysis. Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10864-9. PMID: 8855273 Robbins KE, Weidle PJ, Brown TM, Saekhou AM, Coles B, Holmberg SD, Folks TM, Kalish ML. Molecular analysis in support of an investigation of a cluster of HIV-1-infected women. AIDS Res Hum Retroviruses. 2002 Oct 10;18(15):1157-61. PMID: 12402955

Competing interests: None declared

Specious Arguments That HIV is Not Transmitted by Heterosexual Intercourse 15 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Specious Arguments That HIV is Not Transmitted by Heterosexual Intercourse

In response to some of David Rasnick's comments:
>According to Tony Floyd, we should not debate the contagious/HIV hypothesis of AIDS in this professional medical journal
Did I say that? If I believed it should not be debated then how come my response, which you are criticising, is clearly debating it?
>droves of young people breathlessly taking in every word, looking for any excuse to stop using condoms.
Are you contesting that young people are breathless at the point of making a decision regarding condom use, or whilst reading the BMJ? Or both? The BMJ can be an exciting read sometimes, but not that exciting...
No, young people do not need another reason to not use a condom, nor should they be given one by specious arguments that HIV is not transmitted by heterosexual intercourse. The study in Isreal(1) found that HIV/AIDS-related denial was a factor in reduced condom use by adolescents. Hence my concern.
> "The Evidence That HIV Causes AIDS". The article, which was spared the scrutiny of peer review,
I did not claim that it was peer reviewed, just that it was interesting. It refers to numerous peer reviewed papers such as the findings by Thea et al(2):
"In Zaire, infants with HIV infection have an 11-fold increased risk of death from diarrhea, largely persistent diarrhea, which is often preceded by recurrent episodes of acute diarrhea, malnutrition, or immunosuppression."
> He cites an article from the non-scientific literature titled HIV, AIDS, and the Distortion of Science,
Mea culpa (finally), although it also provides a good source of peer reviewed articles that would appear to support the author's arguments quite nicely.
> profiteering and genocide from medical-industrial complex.
Genocide? Really?
>and personal consultations with Anthony Fauci
Anthony Fauci? Are you sure he is involved in such things? Do you mean Dr Fauci, a member of the National Academy of Sciences and author of Harrison's Principles of Internal Medicine? That's my favourite book!
Please provide some evidence here and now before I line my budgie cage with pages from this hitherto excellent text.
References:
(1) Ben-Zur H. Breznitz S. Wardi N. Berzon Y. Denial of HIV/AIDS and preventive behaviour among Israeli adolescents. Journal of Adolescence. 23(2):157-74, 2000 Apr.Journal of Adolescence. 23(2):157-74, 2000 Ap
(2) Thea DM, St Louis ME, Atido U, Kanjinga K, Kembo B, Matondo M, Tshiamala T, Kamenga C, Davachi F, Brown C, et al. A prospective study of diarrhea and HIV-1 infection among 429 Zairian infants. N Engl J Med 1993 Dec 2;329(23):1696-702

Competing interests: � The use of the word 'Specious' in the title is a flagrant attempt at grandiloquence.

HIV denial 18 February 2003

Peter J Flegg,
Physician
Blackpool Victoria Hospital, FY3 8NR, UK
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Re: HIV denial

People should realise that the main motivation for the dissident stance on HIV/AIDS is ideological, and science is secondary to the argument. The standpoint of those in �HIV denial� has little in common with the scientific method, no matter how prettily �dressed up� they can make it appear. It is based firstly on an unbreakable conviction (faith?) that they are correct, so they ignore data that do not support their own hypothesis, champion data (irrespective of its provenance) that is supportive, misquote and misinterpret data to suit their own ends, and sometimes, as Brian Foley has demonstrated, knowingly mislead and lie. They are past masters at trying to pass off the prevailing scientific view on HIV as being rigidly entrenched in dogma, and like to view themselves as the modern-day Gallileos challenging the Orthodox Church. This flies in the face of what we have learned about HIV over the last two decades using and incorporating new scientific evidence and the systematic evaluation of data to reach a clear consensus.
To adequately address the dissidents� arguments is difficult, since it can too easily become bogged down in detail and seemingly trivial points of order. Questions are seldom answered directly, but always replied to, with the intention of dragging the debate further off course and hopefully into a blind alley. Blatant misrepresentation of the evidence, dressed up to look scientifically plausible, can help persuade interested third parties with no scientific background as to the strength of their case.
As others have pointed out, this view is not of minor importance, since a mixed message about how HIV is transmitted and what it may cause is highly dangerous. Not only does this increase the likelihood of HIV transmission through unsafe sex, but it has persuaded people to discontinue or not start HIV therapy and forgo interventions to limit mother-child transmission, often with disastrous consequences. The dissidents are fond of using emotive language, accusing HIV physicians of using �toxic drugs� (show me some that aren�t), and �genocide� (when it is they who are responsible for persuading the South African Government not to use HIV drugs to save the lives of 40 000 babies each year).
Competing interests: A continued interest in the well-being of HIV infected patients, everywhere.

Re: Apparently, debate and condoms are not compatible 19 February 2003

Martin Delaney,
Founding Director
Project Inform, San Francisco, CA 94103
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Re: Re: Apparently, debate and condoms are not compatible

In his response to Tony Floyd, Mr. Rasnick references an article I wrote, by request, for a newsletter put out by the AIDS Health Project, an AIDS service organization affiliated with the University of California. Does he really expect newsletters to be "peer-reviewed?" Are any of his views on this subject "peer-reviewed?" It's difficult to know what his point is, since after mentioning the article, he merely launches into a personal attack on me. Very scholarly, indeed. If anyone cares, it is true that I made a critical statement about an early AZT trial some 16 years ago. That comment came at a time when I was just beginning my learning path about clinical research. Looking back, I would say that I was merely "mouthing off" on a subject I knew little about. Rasnick then goes on to assert complete nonsense about the incident. I have never filed a Freedom of Information request, as he claims, about the trial. And while my view of AZT did change over time, it was because of the proliferation of later studies which better defined the drug's activities and limitations. He prefers to believe that I was somehow bought off by the government or the pharmaceutical industry.
I never cease to amaze at the denialists' continued obsession with that single early study of AZT, or with the drug itself. There are roughly 18 drugs on the market for the treatment of HIV, most of which escape their wrath. Today, AZT plays only a minor role in the treatment of the disease. One thing that is clear from the last decade's studies, however, is that somehow, adding more of these supposedly "poisonous" drugs produces better, rather than worse results. Surely, if the drugs were causing the physical symptoms as he and Duesberg endlessly bleat, three such drugs would produce worse clinical outcome than a single drug. Instead, the multi-drug combinations have dramatically reduced death rates and greatly extended the lives of those using such therapies. I don't know when the denialists will get it, but their era is over. They have no point and nothing to offer. They have no real data about anything. What they have is a grudge of some kind against the scientific community (for having left them behind?). Unfortunately, there will always be some new or uniformed people who will isten to them and suffer the consequences of their misinformation.
Competing interests: None declared

HIV antibody test is the Achilles heel of AIDS Inc. 19 February 2003

David Rasnick,
Chief Science Officer, Boveran Inc.
San Ramon, CA 94583
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Re: HIV antibody test is the Achilles heel of AIDS Inc.

We have discussed the evidence for and against the hypothesis that HIV and AIDS are sexually transmitted. To be precise, we discussed whether or not antibodies to HIV can be sexually acquired. However, we have not addressed the reliability of the HIV antibody test used in all the studies on transmission. This is a very important consideration because antibodies to HIV play a defining role in whether or not a person has AIDS (Centers for Disease Control and Prevention. 1993, Revised Classification System for HIV Infection & Expanded Surveillance Case Definition for AIDS Among Adolescents & Adults. MMWR 1992; 41: 1-19.). The HIV antibody test is an integral part of the equation that defines someone as having AIDS:
Diarrhea, dementia, Kaposi�s sarcoma, cervical cancer, pneumonia, TB, etc. plus antibodies to HIV = AIDS.
But, Diarrhea, dementia, Kaposi�s sarcoma, cervical cancer, pneumonia, TB, etc. minus antibodies to HIV = Diarrhea, dementia, Kaposi�s sarcoma, cervical cancer, pneumonia, TB, etc.
The entire contagious/HIV hypothesis of AIDS hinges on the HIV antibody test--at least in the USA and Europe. However, AIDS in Africa is virtually always diagnosed without testing for antibodies to HIV because it is just too expensive to do so. A different definition of AIDS for Africa was decided upon by American public health officials at a conference in Bangui, in the Central African Republic in October 1985 (WHO�s Weekly Epidemiological Record 1986; 61:69-76; Quinn, T.C., et al., AIDS in Africa: an epidemiological paradigm. Science, 1986. 234: p. 955-963.). The so-called Bangui definition allows health professionals to diagnosis AIDS in Africa based only on the symptoms and signs that a patient manifests. These symptoms and signs are not new but represent the same old diseases and conditions that have plagued Africans for countless generations before AIDS. For example, in Africa TB, fever, diarrhea, wasting and other diseases of poverty are now called AIDS.
The routinely used methods for diagnosing the presence of HIV in people are the ELISA and western blot antibody tests--not the presence of the virus itself. In fact, there is no direct method of detecting HIV in people (Duesberg, P.H., AIDS acquired by drug consumption and other noncontagious risk factors. Pharmacology & Therapeutics, 1992. 55: p. 201-277; Abbott Laboratories Diagnostics Division, Human Immunodeficiency virus type 1 HIVAB HIV-1 EIA. 1997, Abbott Laboratories: Abbott Park, IL). Some will immediately object and say that the PCR viral load test does just that. But, they would be wrong. We will discuss the numerous problems with the �viral load� test another time.
It may come as a shock to learn that the commercial HIV antibody test is neither standardized nor reproducible. With respect to HIV, the test is meaningless because the results mean different things in different individuals. What�s more, the results mean different things in different laboratories and in different countries (Papadopulos-Eleopulos, E., V.F. Turner, and J.M. Papadimitriou, Is a positive Western blot proof of HIV infection? Biotechnology, 1993. 11: p. 696-707).
The HIV antibody tests are interpreted differently in the United States, Russia, Canada, Australia, Africa, Europe and South America (CDC. Centers for Disease Control and Prevention. Interpretation and Use of the Western Blot Assay For Serodiagnosis of Human Immunodeficiency Virus Type 1 Infections. MMWR 1989; 38 :S1-S7; Voevodin, A. HIV Screening in Russia. Lancet 1992; 399:1548; Maskill, WJ & Gust, ID. HIV-1 Testing in Australia. Australian Prescriber 1992; 15:11-13; de Cock, KM, Selik RM, Soro, B, et al. AIDS Surveillance in Africa: A Reappraisal of Case Definition. BMJ 1991; 303:1185-1189; Zolla- Pazner, S., et al., Reinterpretation of human immunodeficiency virus western blot patterns. N Engl J Med, 1989. 320(19): p. 1280- 1;Burke, D.S., Laboratory diagnosis of human immunodeficiency virus infection. Clin Lab Med, 1989. 9(3): p. 369-92).
For example, a person who is positive in Africa can be negative when tested in Australia, or a person who is negative in Canada can become positive when tested in Africa (HIV Positive?--It Depends Where You Live. Take a Look at the Criteria that Determine a Positive HIV Test Result. Continuum (London) 1995 3(4):20). Another problem is that the same sample of blood when tested in 19 different laboratories got 19 different results on the Western blot test (Lundberg, GD, Serological diagnosis of human immunodeficiency virus infection by Western blot testing. The Consortium for Retrovirus Serology Standardization. JAMA, 1988. 260(5): p. 674-9).
The standard method of establishing the sensitivity and the specificity of a diagnostic test in clinical medicine is to compare the test in question with a valid reference standard. To use an antibody test to label someone with HIV infection and AIDS requires at the very least that the test be shown to be a highly reliable indicator of active HIV infection. However, according to Abbott Laboratories, the maker of the leading HIV antibody test, the company doesn�t even know if their test detects antibodies to HIV, much less HIV itself. "At present there is no recognized standard for establishing the presence and absence of HIV-1 antibody in human blood. Therefore sensitivity was computed based on the clinical diagnosis of AIDS and specificity based on random donors" (Abbott Laboratories. Human Immunodeficiency Virus Type 1. HIVAB HIV-1 EIA. Abbott Laboratories, Diagnostics Division. January, 1997 (66-8805/R5), 5 pages). The insert that comes with the ELISA HIV-antibody test also says that, �AIDS and AIDS-related clinical syndromes and their diagnosis can only be established clinically. �The risk of an asymptomatic person with a repeatably reactive serum sample developing AIDS or an AIDS- related condition is not known.�
In short, the oft stated claim that the HIV antibody test possesses high sensitivity and specificity is based on a comparison with the clinical manifestations of AIDS, or with CD4 cell counts (we can talk about CD4 counts later). Importantly, the sensitivity and specificity of the HIV antibody test were not determined by a comparison with the presence of HIV itself--the usual reference standard. The circular argument guarantees a 100% correlation between antibodies to HIV and AIDS. By definition there can be no AIDS without antibodies to HIV. Conversely, a person who is diagnosed with AIDS is ipso facto infected with HIV, whether or not he has antibodies to HIV (Papadopulos-Eleopulos, E., V.F. Turner, and J.M. Papadimitriou, Is a positive Western blot proof of HIV infection? Biotechnology, 1993. 11: p. 696-707).
Finally, there are over 60 documented ways that a person who has never been in contact with HIV can have false-positive antibodies to the virus. These include: naturally-occurring antibodies, passive immunization, tuberculosis, lupus, kidney failure, hemodialysis, alpha interferon therapy, flu, flu vaccination, Herpes simplex I & II, pregnancy, rheumatoid arthritis, hepatitis, hepatitis B vaccination, tetanus vaccination, organ transplantation, anti-collagen antibodies, autoimmune diseases, cancers, blood transfusions, multiple myeloma, hemophilia, Stevens-Johnson syndrome, heat- treated specimens, the list goes on. (Johnson C. Whose Antibodies Are They Anyway? Factors Known to Cause False Positive HIV Antibody Test Results, Continuum (London), September/October 1996; 4(3):4-5).
David Rasnick
Competing interests: None declared

Re: Promised critique of Foley�s references 19 February 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Re: Promised critique of Foley�s references

> Now to the four references. Reference (R) is of little import to the question > of proof. The paper describes a method for contact tracing of people who > came in contact with HIV positive persons. This paper does not bear on > whether or not HIV or AIDS is sexually transmitted. One could just as > well perform contact tracing of people who come in contact with diabetics, > which would also produce a tracing diagram of those contacts who turned > out to be diabetic themselves, and the much larger number of contacts > who are not diabetic. Such a bizarre undertaking would only make sense > if diabetes were contagious. It is not "bizarre" at all to question whether a disease or syndrome is genetic (tends to affict people who are genetically related to each other), envioronmental (tends to affict people who have some environmental variable in common, such as people exposed to a certain toxin) or contagious (tends to afflict people who have been in contact with other afflicted people). In fact, all three possibilities were fully explored in the first year of the AIDS epidemic in the USA in 1981-1982. All three possibilities have been further explored in subsequent years, and it has become very clear that the aquired immune deficiency syndrome is aquired via acquisition of the primate lentiviruses known as HIV-1 and HIV-2 which can be transmitted from one infected person to another only via very close contact such as blood-blood contact or a transfusion or needle sharing, or sexual contact and not by casual contact such as kissing or sharing eating utensils. It turns out that many diseases and syndromes in fact are influenced by a combination of more than one of these three factors. In the case of diabetes, people can be born with genes that are certain to cause them to be or to become diabetic. Some examples of papers describing genes linked to diabetes are: Huopio H, Otonkoski T, Vauhkonen I, Reimann F, Ashcroft FM, Laakso M. A new subtype of autosomal dominant diabetes attributable to a mutation in the gene for sulfonylurea receptor 1. Lancet. 2003 Jan 25;361(9354):301-7. PMID: 12559865 Ma Y, Tang X, Chang W, Gao L, Li M, Yan W. CTLA-4 gene A/G polymorphism associated with diabetes mellitus in Han Chinese. Chin Med J (Engl). 2002 Aug;115(8):1248-50. PMID: 12515273 Sale MM, FitzGerald LM, Charlesworth JC, Bowden DW, Rich SS. Evidence for a novel type 1 diabetes susceptibility locus on chromosome 8. Diabetes. 2002 Dec;51 Suppl 3:S316-9. PMID: 12475769 Permutt MA, Wasson J, Love-Gregory L, Ma J, Skolnick G, Suarez B, Lin J, Glaser B. Searching for type 2 diabetes genes on chromosome 20. Diabetes. 2002 Dec;51 Suppl 3:S308-15. PMID: 12475768 Some examples of papers describing environmental influences on diabetes are: Chen L, Nyomba BL. Glucose intolerance and resistin expression in rat offspring exposed to ethanol in utero: modulation by postnatal high-fat diet. Endocrinology. 2003 Feb;144(2):500-8. PMID: 12538610 Pastore MR, Bazzigaluppi E, Belloni C, Arcovio C, Bonifacio E, Bosi E. Six months of gluten-free diet do not influence autoantibody titers, but improve insulin secretion in subjects at high risk for type 1 diabetes. J Clin Endocrinol Metab. 2003 Jan;88(1):162-5. PMID: 12519846 There are many human genes that have been described as being either slightly or greatly protective against infection with HIV-1 such as the delta-32 allele of the CCR5 gene, or protective against development of the immune deficiency syndrome once infected such as certain alleles of the SDF-1alpha gene. Ioannidis JP, Rosenberg PS, Goedert JJ, Ashton LJ, Benfield TL, Buchbinder SP, Coutinho RA, Eugen-Olsen J, Gallart T, Katzenstein TL, Kostrikis LG, Kuipers H, Louie LG, Mallal SA, Margolick JB, Martinez OP, Meyer L, Michael NL, Operskalski E, Pantaleo G, Rizzardi GP, Schuitemaker H, Sheppard HW, Stewart GJ, Theodorou ID, Ullum H, Vicenzi E, Vlahov D, Wilkinson D, Workman C, Zagury JF, O'Brien TR. Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. Ann Intern Med. 2001 Nov 6;135(9):782-95. PMID: 11694103 The development of the full AIDS syndrome is extremely highly correlated with infection with pathogens other than HIV-1, such as Mycobacterium tuberculosis and Kaposis' sarcoma virus (HHV-8), because much of the "syndrome" has to do with the ability of these pathogens to do more damage to a person with a weak immune system than to a person with a normal healthy immune system. In fact many of the pathogens that are described as being characteristic of AIDS, such as Pneumocystis carinii, are essentially unable to do any harm to people with normal immune systems. It is certainly not "bizarre" at all to question the links between environment, genes, pathogens and even social factors and diseases or syndromes. Even if the primary cause of a disease or syndrome has been identified, it pays to keep searching for secondary factors that also play roles in the problem. It wan only through studying exposed but uninfected homosexual men in Europe and the USA that the delta-32 allele of the CCR5 gene was discovered. Likewise, there is recent interest in the possibility that another virus (GB virus C), thought to be harmless by itself , is somewhat protective for HIV-infected people. > The lack of correlation between the number of sexual contacts with HIV-positive > partners and risk of becoming HIV-positive was also disclosed in a 1988 CDC > study, which found that, "although most husbands and wives remained uninfected > despite repeated sexual contact without protection, some acquired infection after > only a few contacts" (Peterman, T.A., et al., Risk of human immunodeficiency > virus transmission from heterosexual adults with transfusion-associated infections. > JAMA, 1988. 259: p. 55-58). While David Rasnick seems to consider this to be part of the proof that HIV-1 cannot be sexually transmitted at all, I have already pointed out that it was later found to be correlated with HIV-1 viral load in the "donor" partner. People with higher viral loads tend to transmit the virus more frequently than those with low viral loads. It also does not even hint that HIV-1 cannot be sexually transmitted at all. I wonder if David Rasnick would use similar logic to conclude that if some drunk drivers were observed to drive drunk several times before crashing, while others were observed to crash on the first time they drove drunk, it would prove that people cannot crash a car while under the influence of alcohol? It might turn out that people who drink just a little are able to drive with nearly as much care as the average sober driver, while those who have a blood alcohol content above 0.15% are much more likely to crash. It might further turn out that a driver with a blood alcohol content of 0.005% and 30 years of accident-free driving is less likely to crash than a driver with a blood alcohol content of 0.000% and 2 weeks of driving experience. > Aside from AIDS, what other sexually transmitted disease targets > men and women so completely differently depending on where they live? First of all, AIDS is not a sexually transmitted disease but a syndrome caused by the HIV-1 and HIV-2 viruses which can be transmitted through sexual contact and other mechanisms such as needle sharing and blood transfusion. Secondly, AIDS does not "target" anyone, not does HIV-1 "target" anyone, nor does any pathogen. Infectious diseases afflict people who become infected with the infectious agent whether it is a sexually transmitted bacterium or a water-born amoeba. In the USA, the earliest identified infected induviduals were male homosexuals, IV drug users (more male than female), and Haitian immigrants. The subtype of HIV-1 that was later found to be the cause of this subset of the global pandemic was named HIV-1 M group subtype B which continues to this day to be the predominant subtype in the USA, Haiti, and Europe. The epidemiology of HIV-1 infections and AIDS can be traced on many levels from classical epidemiology to molecular epidemiology, and the data all support the conclusions accepted by the majority of rational humans and flatly rejected by David Rasnick. Just because David Rasnick is confused, does not mean that the conclusions are wrong.

Competing interests: None declared

HIV is Not Good 19 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: HIV is Not Good

A recent study in Ethiopa(1) found that HIV-positive participants were more than 6 times more likely to contract tuberculosis than HIV-negative participants.
As untreated tuberculosis leads to coughing up blood, lung collapse, meningitis and death(2) (amongst other things) can we change this (alleged) debate about HIV=AIDS to something simpler such as:

HIV=Not Good

Any takers?

References:
(1) Wolday D, Hailu B, Girma M, Hailu E, Sanders E, Fontanet AL. Low CD4+ T-cell count and high HIV viral load precede the development of tuberculosis disease in a cohort of HIV-positive ethiopians. Int J Tuberc Lung Dis 2003 Feb;7(2):110-6
(2) http://www.merck.com/pubs/mmanual/section13/chapter157/157g.htm

Competing interests: None declared

A new rapid and accurate test for detecting HIV antibodies 19 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: A new rapid and accurate test for detecting HIV antibodies

A new rapid and accurate test for detecting HIV antibodies was recently approved by the Food and Drug Administration(1), capable of giving a result in only 20 minutes.
A study by Reynolds et al(2) found that the Oraquick(TM) Test resulted in both 100% sensitivity and 100% specificity. No doubt this sort of accuracy won't be maintained in practice, but even with 98% (or even 68%) accuracy HIV diagnosis will benefit by this test's speed and ease of use.
Criticisms of (much older) HIV antibody tests should be reassessed with this in mind.

References:
(1) MMWR Morb Mortal Wkly Rep 2002 Nov 22;51(46):1051-2
(2) Evaluation of a rapid test for the detection of antibodies to human immunodeficiency virus type 1 and 2 in the setting of multiple transmitted viral subtypes. Int J STD AIDS 2002 Mar;13(3):171-3
Competing interests: None declared

Re: HIV antibody test is the Achilles heel of AIDS Inc. 19 February 2003

Dr JK Anand,
retired
retired
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Re: Re: HIV antibody test is the Achilles heel of AIDS Inc.

Dear Editor
Rasnick's letter (Achilles heel....)raises doubts in my mind - at least about the reliability of the diagnosis of AIDS. Unless a)the manufacturers of the AIDS testing kits and b) those responsible for organising and carrying out the tests - i) the governments and ii) the doctors, publish point by point rebuttal of Rasnick's critique, doubts about the wider issues are bound to increase.
I trust that the debate can take place with civility.
Dr JK Anand
Competing interests: � None declared

Exactly what data suggests HIV-1 and/or HIV-2 ELISAs are not accurate? 21 February 2003

Brian T Foley,
HIV Researcher
Los Alamos National Lab, Los Alamos NM 87545
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Re: Exactly what data suggests HIV-1 and/or HIV-2 ELISAs are not accurate?

David Rasnick has regurgitated the standard HIV denialist line, found on all the HIV denialist www sites such as www.virusmyth.com, www.aidsmyth.com and www.aliveandwell.org that the "HIV tests" are unreliable. In fact, there are dozens of test kits approved by the USA FDA which are all as or more reliable than any ELISA test for any other pathogen. No test is ever 100% perfect, but the various ELISA, western blot and other tests for infection with HIV-1 and/or HIV-2 are about as good as they can be. The first tests done in 1984-1985 before cloned reagents were available were much less accurate, sensitive and specific than those done after FDA approval of mass-produced kits which use cloned or synthetic HIV-1 and HIV-2 peptide reagents. There are also dozens of other methods of determining HIV-1 infection which are not approved by the USA FDA, but may be approved by the governments of other countries. The USA is not the only country in the world with the technology to to test for antibodies and a regulatory board with a duty to assure that the technology is porperly used. Here are just two of the hundreds of papers that have been published on this subject:
Clin Diagn Lab Immunol 1996 Jul;3(4):480-2
A field test for the detection of antibodies to human immunodeficiency virus types 1 and 2 in serum or plasma.
Burgess-Cassler A, Barriga Angulo G, Wade SE, Castillo Torres P, Schramm W.
Saliva Diagnostic Systems, Inc., Vancouver, Washington 98682-2444, USA.
ABSTRACT: In response to the need for simple and rapid tests for infectious diseases, we have devised a test for antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 which resembles many contemporary strip-style pregnancy tests in format and ease of use. The test was evaluated with 2,928 serum specimens (1,541 reactive and 1,387 nonreactive) collected and tested at a Mexico City hospital clinic and was compared with a laboratory assay (Abbott) performed simultaneously. The sensitivity and specificity of the test using these serum specimens were 99.68 and 99.71%, respectively (before the code of the blinded study was broken). This compares with 100% sensitivity and 97.55% specificity with the laboratory assay (specificity upon reassay after the code was broken, 99.21%). In a survey of HIV-2 specimens, reactive (positive) specimens were detected in 51 of 51 cases. The test was examined with 21 commercially available (HIV-1) seroconversion panels. The performance of the test was comparable to that of a group of Food and Drug Administration-approved (antibody-based) HIV tests. PMID: 8807218
J Clin Microbiol 2001 Jul;39(7):2572-5
Suitability of a rapid immunochromatographic test for detection of antibodies to human immunodeficiency virus in Ghana, West Africa.
Aidoo S, Ampofo WK, Brandful JA, Nuvor SV, Ansah JK, Nii-Trebi N, Barnor JS, Apeagyei F, Sata T, Ofori-Adjei D, Ishikawa K.
Noguchi Memorial Institute for Medical Research, University of Ghana.
ABSTRACT: In West African countries such as Ghana, efficient human immunodeficiency virus (HIV) testing is a priority in the fight against AIDS. A new immunochromatographic rapid test, Determine HIV-1/2 (Abbott Diagnostics, North Chicago, Ill.), that detects antibodies against HIV type 1 (HIV-1) and/or HIV-2 was evaluated using Ghanaian blood samples. Two hundred four serum and/or plasma specimens were tested. HIV screening was done by a particle agglutination test and confirmed by a Western blot (WB) test as the "gold standard." The results revealed 125 HIV-seropositive AIDS patients, 75 HIV-seronegative healthy individuals, and 4 individuals for whom the HIV-1 result was indeterminate. The results obtained by the Determine HIV-1/2 assay and Diagnostic HIV SPOT (Genelabs), which is currently widely used in many districts in Ghana, were compared with those of the WB test, excluding the four HIV-1-indeterminate samples. The sensitivity of the Determine HIV-1/2 assay was 100%, compared with 98.0% for the HIV SPOT assay. The specificity was 100% for both tests. Determine HIV-1/2 is a single-step assay and was found to be rapid and easy to perform without any special equipment. It was highly sensitive and specific. The kit can be applied without electricity and water supplies, making it suitable for the detection of HIV antibodies especially in the rural areas of Ghana, West Africa. PMID: 11427570
The HIV denialists have clever rhetoric about how the HIV tests are bad, but that same rhetoric can be applied to any serological test for any pathogen. The FDA-approved HIV tests are as good as the tests for any other pathogen.
If David Rasnick and/or any other "dissidents" truly have any data to indicate that the HIV tests are less reliable than reported, or that HIV-1 cannot be sexually transmitted, they should present it in a clear and important way. "Debating" on the internet or anywhere else is not going to do anything, really. Taking their cause to a the politicians of a country such as South Africa, is certainly good for gaining publicity, but does nothing to advance the real scientific knowledge of the issue. David Rasnick claims that Christine Johnson published a paper in Continuum magazine that claimed that there are over 60 conditions that can cause a false positive HIV test. It may be true that Continuum published such a paper, but the real issue is what data was that paper based on? What EXACTLY is the rate of false positive ELISA and which ELISA test kit was used, as the basis of the claim that pregnancy can cause a false-postive HIV-1 ELISA?
Horowitz GM, Scott RT, Hankins GD.
Results of a prenatal screening program for the human immunodeficiency virus in a cross-sectional population.
J Reprod Med. 1991 Nov;36(11):773-8. PMID: 1765954
Found 6 of 3,241 pregnant women gave a false positive ELISA. This is 0.19% which is similar to the overall false-positive rate. Does David Rasnick know of another method that could be used to reduce the false positive rate from 0.19% to less than 0.005%? What is his recommendation for improving the accuracy, specificity, and sensitivity of HIV-1 ELISA? Does he have data to show that it is cost-effective to spend $2 or $200 per tested patient to increase the accuracy or specificity? In an ideal world the resources available for public health programs might be infinite, but in the world we live in, there are countries that spend less than $2 per year per capita on all health programs combined, which doesn't leave many options for doing 20 tests on each pregnant woman to increase the accuracy from 99.81% to 99.995%. In those countries, it may not make much difference if 2 or even 10 people per thousand are falsely diagnosed if there is no treatment available anyway. In such counrties, the emphasis must be focussed more on prevention than on treatment, but David Rasnick would like to convince those countries that HIV-1 cannot be sexually transmitted.
Competing interests: None declared

Do not be seduced by the sirens of dissidence 21 February 2003

Peter J Flegg,
Physician
Blackpool Victoria Hospital UK FY3 8NR
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Re: Do not be seduced by the sirens of dissidence

I am afraid Dr Anand (Re: HIV antibody test is the Achilles heel of AIDS Inc, 19th February) has demonstrated exactly why the message from HIV dissidents like David Rasnick are so dangerous. By using a combination of what is essentially plausible-sounding quotes from �scientific� references, Rasnick has managed to sow seeds of doubt in the mind of someone who should be able through objective scientific thinking to distinguish fact from disinformation. Instead of questioning Rasnick�s sources, Anand concludes that as the argument seems superficially plausible, it is up to everyone else concerned to publish a point by point rebuttal of Rasnick�s critique.
Anand may not realise it, but rebuttals of points similar to Rasnick�s have been made time and time again, but the dissidents ignore the message and refuse to behave like decent scientists should by modifying their views in the face of new evidence. Rasnick talks about problems with HIV testing, and quotes several sources, most of which are either not peer-reviewed or which are so old as to have been superceded by new data (of which he is no doubt aware but prepared to ignore). Of course HIV tests are not perfect, with 100% sensitivity and specificity, but recent assays approach this level and are some distance away from early assays used in the 1980s and often bedevilled by low (but unacceptable) false positivity rates.
Rasnick quotes an old reference from the best known dissident, Peter Duesberg, as saying there is no direct method for detecting HIV in people. Dissidents today do not like to talk about it, but Duesberg himself has recanted on his previously held views on HIV, and accepts its existence in humans. Indeed he has tried to claim a "reward" for proving the existence of HIV (one of those "rewards" that will never be given, since the dissidents offering it refuse to entertain that it has ever been "won").
Rasnick talks of HIV being a prerequisite for diagnosing AIDS, as though this somehow demeans the test. AIDS is a syndrome defined in an HIV -positive individual as the occurrence of illnesses associated with advanced immunodeficiency, which occur in the absence of alternative reasons for immunodeficiency. So if an HIV positive man gets pneumocystis pneumonia, he has AIDS, but if an HIV-negative man who has had a bone marrow transplant gets PCP, we do not call this AIDS. I see no inconsistency, and neither do 99.9% of other clinicians. A corollary would be in the case of Hepatitis B � it can cause cirrhosis, and in a man with chronic hepatitis B and no other history of hepatotoxic drugs or other diseases, I am quite prepared to say he has chronic liver disease from hepatitis B. If an alcoholic without evidence of chronic hepatitis infection gets cirrhosis, I am prepared to say he has alcoholic liver disease.
Rasnick points out historical inconsistencies in the interpretation of Western Blot assays as "evidence" that the testing procedure is flawed. Dissidents imply that a single test can be employed as a one-off procedure to arrive at a diagnosis, and the patient is left with this result, either liking it or lumping it. Nothing is further from the truth. No-one makes a clinical diagnosis of HIV without adhering to a clear protocol, which consists of initial screening with a minimum of 2 ELISAs looking for different patterns of antigens and subsequent confirmation using either Western Blot or further ELISAs. In the instance of uncertainty with the assays (there can be �window periods� and false positives) the tests will be repeated, and repeated as often as is required. All those who are �HIV positive� in Western countries will have other corroborative tests performed in addition � immunological tests, viral quantification by by PCR, NASBA or bDNA probes, sequencing to determine genotype and often baseline drug resistance assays looking for amino-acid substitutions indicative of drug resistance, and sometimes HIV culture. The fact that there exist differences in interpretation of the pattern of reactivity on Western Blot testing to HIV-1 gene products should fool no-one. Rasnick quotes papers on Western Blot which are some 14 years old, studiously ignoring newer data on its specificity (97.8%) and newer gudelines for interpretation of the assay which remove the requirement for reactivity to p31 or p66 (Revised Recommendations for the Prevention of Human Immunodeficiency Virus (HIV) Transmission by Blood and Blood Products. Bethesda, Md: Center for Biologics Evaluation and Research, Food and Drug Administration; April 23, 1992).
Attempts to imply that the manufacturers of HIV assays themselves do not think HIV exists are lame, to say the least. Virtually every diagnostic assay will have a legal disclaimer of some sort specifying that the tests should not be the sole basis on which a disease is diagnosed. This is because no matter how good a test is it will never be 100% perfect.
Rasnick�s indicates that HIV assays, of which there are many, have "60 documented ways" in which a person can have "false positive" antibodies (I presume he means a false positive HIV antibody test). Usually dissidents quote a figure of 70+ causes for this. The list of causes is old (many of the newer assays do not show reactivity to some of the putative causes), tautological (autoimmune disorders appearing perhaps a dozen times), incorrect (references to specific publications do not match the stated data) and sometimes ridiculous. It is not disputed that false positive HIV assays occur, but the dissident implication is that this means the test is useless, or that in a country such as Africa all HIV positive results must be the consequence of pregnancy, or malnutrition, or TB (forgetting that antenatal screening in the UK has shown precious little problems, or that epidemiologically these conditions do not coincide with highest areas of seroprevalence). One classic example was the claim that malaria caused Southern Africa�s HIV postive problem, only for the dissidents to wipe the egg off their faces when they realised that in South Africa, malaria was seasonal and confined to Northern Kwa- Zulu Natal only.
So why is the dissidents� message so seductive? There are many who would love to believe that HIV has little to do with AIDS, from the individual patient who may be in denial about lifestyle and behavioural risks, ranging all the way up to heads of governments who would like to dissociate the problems their country faces from a disease that is often perceived as being linked with promiscuous sex, race and having implications for other issues such as tourism. Let us hope that the attempts by dissident "scientists" like David Rasnick to promote his dangerous agenda to fail.
Competing interests: None declared

Apologies. HIV Testing Was Also Accurate 15 Years Ago 22 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Apologies. HIV Testing Was Also Accurate 15 Years Ago

In my response dated 19th February I cited a recent finding by Reynolds et al(1), in which they found 100% sensitivity and 100% specificity for a new HIV antibody test.
I did not mean to imply that older tests were any less accurate (or at least not significantly so). Accurate tests in fact were in use in the 1980's, as shown by Maskill et al (2). The significance of the newer test lies more so in its ease of use and rapid result, which can be determined on the spot by a trained operator in as little as 20 minutes.
Facts would appear to be the 'Achilles Heel' in arguments that HIV testing isn't accurate.

References
(1) Reynolds SJ, Ndongala LM, Luo CC, Mwandagalirwa K, Losoma AJ, Mwamba KJ, Bazepeyo E, Nzilambi NE, Quinn TC, Bollinger RC. Evaluation of a rapid test for the detection of antibodies to human immunodeficiency virus type 1 and 2 in the setting of multiple transmitted viral subtypes. Int J STD AIDS 2002 Mar;13(3):171-3
(2) Maskill WJ, Crofts N, Waldman E, Healey DS, Howard TS, Silvester C, Gust ID. An evaluation of competitive and second generation ELISA screening tests for antibody to HIV. J Virol Methods 1988 Oct;22(1):61-73

Competing interests: None declared

Reply to Floyd and Foley 23 February 2003

David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583
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Re: Reply to Floyd and Foley

Tony Floyd points to the recently approved 20-minute HIV antibody test that produces identical results obtained with standard HIV antibody tests. He says that "Criticisms of (much older) HIV antibody tests should be reassessed with this in mind." However, the question is not whether different antibody tests can be tuned to give the same results, but whether the results of any HIV antibody test is a reliable indication of infection with HIV and, more importantly, whether a positive result means that a person will eventually develop AIDS and die. That is the crux of my skepticism and criticism of the HIV antibody tests.
In responding to my fanciful story of contract tracing of people who came in contact with a diabetic, Foley says that, "It is not 'bizzare' at all to question whether a disease or syndrome is genetic..., environmental..., or contagious." That is quite true, of course. However, his statement illustrates nicely how epidemiological correlations can mean whatever you want them to mean. Epidemiological correlations may be consistent with a particular hypothesis (or even conflicting hypotheses) but they cannot answer the questions Foley raises. For example, a phenomenon that appears to be clustered could be consist with genetic, environmental, and contagious hypotheses. But the question is, which if any of these hypotheses is correct? That's why epidemiologists have it drilled into their heads at school that correlations do not prove causation. Yet, epidemiological correlations between antibodies to HIV and AIDS are offered as the strongest evidence that HIV cause AIDS.
On the other hand, while correlations do not prove causation, the absence of a correlation that should be present if a hypothesis is true, is indeed strong evidence that the hypothesis is wrong. For example, I have cited the numerous paradoxes and inconsistencies that arise when the epidemiological data for HIV and AIDS are compared with what one would expect to find for a sexually transmitted disease.
To reiterate, the claimed "extremely" high correlation between antibodies to HIV and AIDS is a simple artifact of the definition of AIDS:
Antibodies to HIV plus AIDS-defining disease or condition equals AIDS.
Absence of HIV antibodies precludes AIDS.
At the risk of over-emphasizing the point, had the CDC defined AIDS as pneumonia in people with blue eyes, then only blue-eyed people with pneumonia would have AIDS. Using that peculiar definition, people with brown eyes could still get pneumonia but would be spared from even the possibility of getting AIDS--unless, of course, they wore blue-tinted contact lenses.
David Rasnick
Competing interests: None declared

Do AIDS drugs deserve credit for extending life? 23 February 2003

David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583
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Re: Do AIDS drugs deserve credit for extending life?

Martin Delaney says that, "the multi-drug combinations have dramatically reduced death rates and greatly extended the lives of those [HIV-positive people] using such therapies". This is a very common assertion made these days about the wonderful life- saving benefits of the admittedly highly toxic anti-HIV drugs. Let's take a look at the evidence and see if Delaney's unrestrained enthusiasm for the antiretrovirals is justified.
First, we must look at the CDC's HIV/AIDS Surveillance Reports to see how AIDS has changed in the USA over the past two decades. The CDC data show that AIDS peaked in 1992 and has been going down steadily ever since (see for example the cover of the 1997 year end edition of the HIV/AIDS Surveillance Report). The mortality rate from AIDS is dropping because AIDS has been declining in the USA since 1992, years before the introduction of HAART, the multi-drug combinations that Delaney touts. The apparent life-saving benefits of the HIV-protease inhibitor cocktails is a consequence of the simple fact that these drugs have appeared on the scene long after AIDS peaked in the USA, during a period when the mortality due to AIDS was naturally in decline (Centers for Disease Control and Prevention (1997): U.S. HIV and AIDS cases reported through December 1997; Year-end edition. 9: 1-43).
Another reason for the decline in AIDS deaths is the CDC's re- definition of what constitutes AIDS in the USA. Since the mid 1990s, well over half of all new AIDS cases in the USA represented people who weren�t even sick. As of 1993, all you needed to qualify as an AIDS case were results from two lab tests: be immune to HIV, that is have antibodies to the virus, and have fewer than 200 CD4 cells per microliter of blood or a CD4 percentage less than 14 (Centers for Disease Control and Prevention. 1993, Revised Classification System for HIV Infection & Expanded Surveillance Case Definition for AIDS Among Adolescents & Adults. MMWR 1992; 41: 1-19).
In 1997, 36,634 people (61% of all new AIDS cases) were classified under this non-disease category (Table 12 of Centers for Disease Control and Prevention (1997): U.S. HIV and AIDS cases reported through December 1997; Year-end edition. 9: 1-43). We can no longer follow the nationwide trend of including healthy people as AIDS cases after 1997 because the CDC stopped listing the AIDS-indicator diseases and conditions (formerly Table 12) in its HIV/AIDS Surveillance Reports.
However, San Francisco continues to report AIDS cases according to specific AIDS-defining diseases. The San Francisco Quarterly AIDS Surveillance Report for 2000 shows in Table 10 on page 8 that 47.7 percent of all AIDS cases from 1980 through 2000 were diagnosed with AIDS according to the two lab tests of the 1993 definition change (Katz M, Schwarcz S, Hsu L, Parisi MK, Chu PL, Scheer S (2000): Quarterly AIDS Surveillance Report. Journal The AIDS Surveillance Report is accessible via internet: www.dph.sf.ca.us/PHP/AIDSSurvUnit.htm). Since this is a cumulative number, which combines all AIDS cases under four different definitions of AIDS, well over half of all people (mostly gay men) in San Francisco that are currently being labeled as AIDS cases have no AIDS-defining disease.
The CDC has a rule that an AIDS case is classified according to the earliest definition that applies. Because the majority of new AIDS cases in the USA are classified according to the non-disease criteria of the CDC's 1993 definition change, they do not have any of the colossal list of AIDS diseases--from diarrhea to dementia, pneumonia to cervical cancer--required by earlier definitions. Thus, the majority of new AIDS cases are disease-free (healthy) people. In spite of the 1993 definition change, with its inclusion of large numbers of healthy people as AIDS cases, the figure on page 1 of the Quarterly AIDS Surveillance Report for San Francisco cited above shows that the number of new AIDS cases for 2000 was at the same level as 1982 (below 50 cases), so few you could know them all by name.
As a consequence of the CDC's 1993 definition of AIDS, over half of the people treated with the anti-HIV drug cocktails in the USA since 1996 (the year the HIV protease inhibitor cocktails became available) were healthy when they started taking the drugs. Delaney, the mainstream AIDS press and AIDS researchers are crediting HAART with prolonging the lives of these healthy people. Sadly, these healthy people taking HAART don't stay healthy long. They eventually get sick from the drugs and die if they stay on them long enough (Levy JA (1998): Caution: should we be treating HIV infection early? The Lancet 352: 982-983; Duesberg PH, Rasnick D (1998): The AIDS dilemma: drug diseases blamed on a passenger virus. Genetica 104: 85-132; Lauritsen J (1990): Poison by Prescription-The AZT Story. New York, Asklepios Press; Altman L: U.S. Panel seeks Changes in Treatment of AIDS Virus. New York Times 2001;February 4: 16; Altman L: U.S. warns doctors to limit use of anti-HIV drug. New York Times 2001;Jan. 5: A12).
Next, an examination of the clinical trials conducted to measure the clinical benefits of the anti-HIV drugs.
David Rasnick
Competing interests: None declared

Rasnick has already PUBLISHED that HIV can be transmitted by sex. 24 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Rasnick has already PUBLISHED that HIV can be transmitted by sex.

Whilst looking for even more evidence that HIV causes AIDS, that HIV can be sexually transmitted, that everyone should not share needles or practice unsafe casual sex etc. etc...
I came across Rasnick's own article, which, half way down the page states that:

"Since the virus is very rare ... and very hard to transmit sexually"
VERY HARD to transmit sexually!!! When did you change your mind about HIV? You've stated here that it isn't sexually transmitted, yet only a few years ago you co-authored a document saying that it was?
Are there any of your other claims that you have changed your mind about recently?
Even if some research has found transmission rates low, what about when it does transmit? Such as the case of a child who was raped by a HIV-positive man(2). The virus in the rapist and victim both contained a unique amino acid deletion that contributed to the rapist's conviction.

References
(1) Duesberg P, Rasnick D. The AIDS dilemma: drug diseases blamed on a passenger virus. Genetica 1998;104(2):85-132
(2) Machuca R, Jorgensen LB, Theilade P, Nielsen C. Molecular investigation of transmission of human immunodeficiency virus type 1 in a criminal case. Clin Diagn Lab Immunol 2001 Sep;8(5):884-90
Competing interests: None declared

AIDS and drugs - a response to David Rasnick 24 February 2003

Peter J Flegg,
Physician
Blackpool Victoria Hospital. UK Fy3 8NR
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Re: AIDS and drugs - a response to David Rasnick

David Rasnick titles his latest contribution "Do AIDS drugs deserve credit for extending life?", but pointedly fails to address the question he has raised. It is easy to see why, since he can provide no evidence for his claims. Instead he talks about CDC definitions of AIDS, as though this is relevant, or that changes in this definition somehow invalidate the clearly apparent benefits from the drugs.
Yes, the AIDS case definition has changed, as have definitions for other conditions over recent years, such as myocardial infarction for example. If he is trying to discuss the HIV drugs "extending life", he should concentrate on AIDS mortality, which he fails to do. If I wish to discuss whether statins prolong survival in those with ischaemic heart disease, I do not discuss differing definitions of myocardial infarction according to troponin levels, but look at mortality statistics.
A little history lesson seems to be in order. HIV therapies were introduced in the late 1980s, firstly with single, then dual therapy. Studies in symptomatic patients showed the benefit in this approach, but real inroads were only made with the introduction of triple drug regimens from 1995 onwards.
A look at the reported adult AIDS deaths in the United States shows a steady rise which slows after 1990, reaching a peak of nearly 51000 deaths in 1995, then a dramatic fall to under 9000 deaths in 2001(1). These dates and figures fit extremely well with the experience of clinicans on the ground who were treating HIV patients with HIV drug regimens, and for Rasnick to dissemble about changing AIDS definitions is merely a diversionary tactic.
Rasnick's claim that deaths are caused by the HIV drugs ("Sadly, these healthy people taking HAART don't stay healthy long") also fails. Not only have AIDS deaths have fallen by over 80%, but this has happened during a period when antiretrovirals have been prescribed ever more widely (a seven-fold increase in global volume of sales since 1995). If it is the drugs that are lethal, they seem to have mysteriously lost much of their toxicity.
Rasnick quotes a leading HIV practitioner as having doubts about the impact of new therapies(2). Or rather he misquotes him, since JA Levy is discussing in his article (from 5 years ago) the initiation of therapy in early, asymptomatic HIV infection which as anyone with experience of treating HIV will tell you, is a quite different prospect from the use of therapy according to recognised guidelines. But we should get used to this approach from the dissidents - they will use misquotes, out of context quotes, out of date references, and sources that sound impressive but are often written by non scientists (or scientists from a field unrelated to HIV medicine) in long since defunct dissident magazines with grand titles.
(1)Centers for Disease Control & Prevention National Center for HIV, STD, and TB Prevention Divisions of HIV/AIDS Prevention. Table 21. U.S. HIV and AIDS cases reported through December 2001. Year-end edition Vol.13, No.2.
(2)Levy JA. Caution: should we be treating HIV infection early? The Lancet 1998; 352: 982-983
Competing interests: None declared

Scientists must always be able to change their minds 24 February 2003

David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583
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Re: Scientists must always be able to change their minds

Dear Editor,
Brian Foley wants to know, "When did [I] change your mind about HIV? You've stated here that it isn't sexually transmitted, yet only a few years ago you co-authored a document saying that it was? Are there any of your other claims that you have changed your mind about recently?"
I'm flattered that Foley cites our Genetica paper (Duesberg PH, Rasnick D (1998): The AIDS dilemma: drug diseases blamed on a passenger virus. Genetica 104: 85-132) as evidence supporting his position that HIV is sexually transmitted. Again, one can find the quote Foley uses in the abstract of that lengthy paper. I encourage people to read the paper in depth. It can be found at:
http://www.duesberg.com/papers/pddrgenetica.html
where you can download it as a pdf document.
During the mid 1980s, I accepted without skepticism (I was a young scientist, eager to make HIV protease inhibitors at the time) the contagious/HIV hypothesis of AIDS. I had assumed that Gallo and his colleagues knew what they were talking about. That was a mistake I hope never to make again.
One of the advantages of being a scientist is that one can change his mind as his understanding of the evidence changes. Foley seems to hold that against me. Is he prepared to change his mind as the evidence warrants?
I gave up acceptance of the contagious/HIV hypothesis of AIDS grudgingly and stepwise. In 1985, I was privileged to listen to a group of San Francisco Bay area virologists discussing HIV. The thing that struck me most was a discussion of the viral titer in AIDS patients--the titer was zero. HIV was not to be found in AIDS patients using standard methods of detection. That's why to this day, antibodies to HIV are used to label a person with AIDS and not detection of the virus itself. (We will talk about PCR viral load later.)
Recalling the efforts to identify the virus that caused polio, I interpreted the inability to measure HIV in AIDS patients to the fact that Gallo had simply gotten (from Montagnier) the wrong virus. Nevertheless, I still accepted that a virus (a different virus) caused AIDS, and the rest of the dogma. I assumed that the right virus would eventually be discovered. However, sometime during 1987 I realized that the evidence was overwhelming against AIDS being contagious and sexually transmitted--HIV had already been put in the dust bin. I didn't know what was causing AIDS, but it was not an infectious agent and certainly not HIV.
I began reading everything I could lay my hands on regarding the paradoxes and outright contradictions resulting from the contagious/HIV hypothesis of AIDS. In 1988, I came across Peter Duesberg's paper in Cancer Research, published the year before (Duesberg PH (1987): Retroviruses as carcinogens and pathogens: expectations and reality. Cancer Res 47: 1199-1220). The paper was like a legal document, dismantling brick by brick the hypothesis that retroviruses in general, HIV in particular, were pathogenic to humans. That paper was like a revelation. The evidence since has driven a mountain of nails into the coffin of the contagious/HIV hypothesis of AIDS.
Knowing my own struggle confronting the contagious/HIV hypothesis of AIDS, I try to help people ease into asking their own questions about it by starting with what the mainstream itself is saying and pointing out the problems with that. For example, in the Genetica paper that Foley cites, the mainstream says that HIV is sexually transmitted but it is very hard to transmit. We and others ask, what does very hard to transmit mean for the hypothesis? It pulls the rug out from under it.
As a scientist, I have no beliefs about AIDS. (Beliefs are things taken to be true in the absence of evidence.) However, I do have views and opinions. I hope that I will always be able to change my views and opinions as my understanding of the evidence changes.
David Rasnick
Competing interests: None declared

Foley has never cited Genetica. Why did you change your mind again? 25 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Foley has never cited Genetica. Why did you change your mind again?

Rasnick's recent response entitled Scientists must always be able to change their minds clearly states:

"Foley cites our Genetica paper"
There are 14 responses from Foley above, not one of them cites or so much as alludes to an article from Genetica.
Was it my Genetica reference that prompted your comments? I pointed out that your 1998 paper states that the virus CAN be transmitted sexually. I asked when did you change your mind, I did not challenge your RIGHT to change your mind! My question is all the more pertinent now that your response has discussed all of the 'evidence' that you came across 10-15 years ago, and yet you put your name to a contagious theory in 1998.
You should check your facts a little closer, and reference the correct person. Oh, and if you changed your mind pre-1998, when did you change back post-1998, and what good evidence-based decision making prompted both decision?

Competing interests: None declared

I stand corrected 26 February 2003

David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583
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Re: I stand corrected

Dear Editor,
Tony Floyd has correctly pointed out a factual error. I have confused him with Brian Foley in my letter titled �Scientists must always be able to change their minds�. I am eager to apologize to both Floyd and Foley for my mistake. I was afraid that I would windup confusing them. The letter should have been directed to Tony Floyd. I will try harder to more careful.
David Rasnick
Competing interests: None declared

Duesberg Must Have Also Changed His Mind. 26 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Duesberg Must Have Also Changed His Mind.

Hard to transmit does not mean NOT transmissible. You're unlikely to die of a heart attack at any given moment, so does that mean we can conclude that heart attacks are not fatal?
In the response Scientists must always be able to change their minds:

"During the mid 1980s, I accepted ... the contagious/HIV hypothesis of AIDS"
Then:

"during 1987 I realized that the evidence was overwhelming against AIDS being contagious and sexually transmitted"
Then in the 1998 Genetica paper:

"Since the virus is ... very hard to transmit sexually"
Until now when the pendulum would appear to have swung again, denying any infectious cause for AIDS.
From the same response comes:

"Duesberg PH (1987): ... That paper was like a revelation."
It must not have been a convincing revelation, because Duesberg was also an author of the 1998 paper that stated that the virus is hard to transmit, and therefore transmissible! Has he also changed his mind again?
Competing interests: None declared

The anti-HIV drugs 26 February 2003

David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583
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Re: The anti-HIV drugs

I must apologize for the length, but the seriousness of the subject demands a degree of thoroughness.
We begin with the well-recognized severe toxicities of the anti-HIV drugs. This will set the stage for the discussion that follows.
The nucleoside analogs were developed in the 1960s as cytotoxic chemotherapy for cancer. It is often forgotten that these drugs are not only inhibitors but also substrates of the human enzymes responsible for DNA synthesis. As substrates, the drugs are incorporated into growing DNA chains, thus terminating further polymerization, which kills or otherwise injures the cells. All of the anti-HIV nucleoside analogs come with a black box label warning of severe life-threatening toxicities, which include: a profound general depression of the immune system, anemia, lactic acidosis, liver damage, among numerous other unpleasant effects.
As everyone knows, the purpose of cytotoxic chemotherapy is to quickly kill as many cancer cells as possible without killing the patient. That's why chemotherapy for cancer is stopped after only days, weeks, or months. Yet, the standard of care for HIV positive patients is to prescribe the DNA chain-terminating cytotoxic chemotherapies (some of which, e.g. AZT, are still being use as short-term cancer chemotherapy) for life. Prescribing these powerfully immune suppressive drugs to hundreds of thousands of HIV-positive people for life in an effort to treat an immune suppressive disease (AIDS) represents not just a monumental paradox but is an ongoing medical tragedy of colossal proportions.
The non-nucleoside analog nevirapine is no less toxic. It has its own black box label warning of life-threatening liver toxicity and life-threatening skin reactions. The HIV protease inhibitor cocktails have a whole conference devoted to their myriad toxicities. Recently, a book devoted to the toxicity of HAART (Highly Active Anti-Retroviral Therapy) (Lark Lands, (2002) A Practical Guide to HIV Drug Side Effects, first edition, ISBN 0-9730715-2-4) was made available online http://www.catie.ca/sideeffects_e.nsf.
It is not surprising that the well-known mechanisms of action and severe toxicities of the anti-HIV drugs have produced dissidents within the ranks of mainstream AIDS researchers. These mainstream dissidents take issue with the claim that the anti-HIV drugs do more good than harm. A list of examples follows:
1) Seligmann M, et al.
Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Lancet 343: 871-881 (1994)).
"The results of Concorde do not encourage the early use of zidovudine [AZT] in symptom-free HIV-infected adults. They also call into question the uncritical use of CD4 cell counts as a surrogate endpoint for assessment of benefit from long-term antiretroviral therapy". -------------------------
2) Fleming TR
Surrogate markers in AIDS and cancer trials. Statistics in Medicine 13: 1423-1435 (1994)
In the Concorde Study, there was a 25% higher mortality rate among those who took AZT early compared to those who took the drug later. The pressures to use AZT treatment in asymptomatic persons with HIV were not supported by this and other long-term clinical trials. -------------------------
3) Jay Levy, UCSF
AIDS surrogate markers, is there truth in numbers?, JAMA vol 276, pages 161-162 (1996)
Commenting in 1996 on Abbott's report of increased survival in its HIV protease inhibitor clinical trial Levy said: "...can one really report a 50% increase in survival based on only 6 months of treatment and results that reflect 4.8% (treated) vs 8.4% (untreated) of the subjects studied? ...With all the hoopla about antiviral drugs, and you get any virologist aside and they'll say this is not how we are going to win, it's high time we look at the immune system"
Two years later Levy was still unconvinced that the anti-HIV drugs do more good than harm.
4) Jay Levy
Caution: should we be treating HIV infection early?, The Lancet 352: 982-983 (1998).
"The clinical state (if the person is without symptoms) is not a major detriment [to administering anti-HIV drugs]: it is the [viral load] numbers that appear to decide the therapeutic course. I take issue with that approach."
"[T]hese drugs can be toxic and can be directly detrimental to a natural immune response to HIV... This effective antiviral immune response is characteristic of long-term survivors who...have not been on any therapy. ...[T]he current antiviral therapies...do not bring about the results achieved by a natural host anti-HIV response. This immune response, observed in long-term survivors, maintains control of HIV replication without the need for antiviral treatment." -------------------------
5) A. N. Phillips and G. D. Smith,
Viral load and combination therapy for human immunodeficiency virus, The New England Journal of Medicine 336, no. 13: 958-959 (1997)
"No randomized trials in asymptomatic patients have established that those treated early survive any longer than those for whom treatment is deferred. Extended follow-up of patients in one trial, the Concorde study, has shown a significantly increased risk of death among the patients treated early. The suggestion is that the situation is different for combination therapy. But where is the evidence...?"
"There is no more hard evidence now of the benefits of early therapy than there was in 1990. We need new randomized trials to determine whether the notion that was probably not true in the era of [AZT] monotherapy-that early therapy prolongs survival as compared with deferred therapy-is now true." ----------------------------
6) Don Abrams, SF General Hospital
Tanaka, M. "Abrams cautious on use of new AIDS drugs", Synapse vol 4, pages 1 & 5 (1996)
"In contrast with many of my colleagues..., I am not necessarily a cheerleader for anti-retroviral therapy. I have been one of the people who's questioned, from the beginning, whether or not we're really making an impact with HIV drugs and, if we are making an impact, if it's going in the right direction."
"I have a large population of people who have chosen not to take any antiretrovirals... They've watched all of their friends go on the antiviral bandwagon and die, so they've chose to remain na�ve [to therapy]. More and more, however, are now succumbing to pressure that protease inhibitors are 'it'... We are in the middle of the honeymoon period, and whether or not this is going to be an enduring marriage is unclear to me at this time..." -----------------------
7) The Italian Register for HIV Infection in Children
"Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy" AIDS 13: 927-933 (1999)
"The probability of developing severe disease at 3 years of life was significantly higher in children born to [AZT+] mothers...than in those born to [AZT-] mothers... . The same pattern was observed for severe immune suppression: the probability of developing severe immune suppression was significantly higher in the children born to [AZT+] mothers... than born to [AZT-] mothers... . Finally, survival probability was lower in children born to [AZT+] mothers...compared with children born to [AZT-] mothers..."
In short, if a mother takes AZT during pregnancy, her newborn is much more likely to get severely sick and die by age 3 than a newborn whose mother did not take AZT during pregnancy. ---------------------
8) Amanda Mocroft et al.
"Anaemia is an independent predictive marker for clinical prognosis of HIV-infected patients from across Europe" AIDS 13: 943-950 (1999)
These authors looked at 6725 patients from EuroSIDA, a prospective study in 52 centers across Europe.
They "found a strong relationship between haemoglobin, CD4 lymphocyte count and risk of death."
Their results showed that patients with severe anemia had from 30 to 90 times the risk of death compared to patients with a normal hemoglobin level.
There is no mystery to this extraordinarily high risk of mortality since the authors provide the answer themselves:
"Patients with mild or severe anaemia were significantly more likely to have taken zidovudine [AZT] at some stage... . In addition, patients with anaemia, mild or severe, were much more likely to have been diagnosed with AIDS..."
"We found that 78.2% of the patients with mild or severe anaemia at baseline had received zidovudine [AZT]..."
Anemia is listed in the black box warning label as one of the toxic consequences of taking AZT. --------------------------
9) O. A. Olivero et al.
"Incorporation of zidovudine into leukocyte DNA from HIV-1- positive adults and pregnant women, and cord blood from infants exposed in utero" AIDS 13: 919-925 (1999)
"...further study of the biological consequences of [AZT]-induced DNA damage in the human population is warranted." --------------------
10) R. van Leeuwen, et al.
"Additive or sequential nucleoside analogue therapy compared with continued zidovudine monotherapy in HIV-infected patients with advanced disease does not prolong survival: an observational study" The Journal of Infectious Diseases 175, 1344-1351 (1997)
"Additive or sequential treatment was associated with an increased risk of death." --------------------
11) S. Lindb�ck, et al.
"Long-term prognosis following zidovudine monotherapy in primary HIV type 1 infections", The Journal of Infectious Diseases 179, 1549-1552 (1999)
"Zidovudine treatment initiated during primary HIV (PHIV) infection did not improve long-term outcome after symptomatic PHIV infection." ---------------------
12) K. Brinkman, et al.
"Mitochondrial toxicity induced by nucleoside-analogue reverse- transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy", The Lancet 354, 1112-1115 (1999)
"...nearly all side-effects that have been attributed to the use of NRTIs, such as polyneuropathy, myopathy, cardiomyopathy, pancreatitis, bone-marrow suppression, and lactic acidosis, greatly resemble the spectrum of clinical manifestations seen in inherited mitochrondrial diseases." -------------------
13) Anthony Fauci, Director NIAID, NIH
Quoted in "1997 Year of the Crash: Despite New AIDS Drugs, Many Still Lose the Battle" by Sheryl Gay Stolberg, New York Times, Friday, August 22, 1997, Page 1.
"'There is an increasing percentage of people in whom, after a period of time, the virus breaks through,' said Dr. Anthony Fauci, director [NIAID]. 'People do quite well for six months, eight months or a year, and after a while, in a significant proportion, the virus starts to come back.'"
"No one knows the true extent of the problem, but Fauci estimates that when these cases of 'viral breakthrough' are accounted for, the failure rate of the new drug cocktails may eventually run as high as 50 percent."
Fauci's failure rate was really 100% in the AIDS cases that actually have symptoms of disease. Recall that since 1993, 50% of AIDS cases (as mentioned previously) have no symptoms of disease (Centers for Disease Control and Prevention (1997): U.S. HIV and AIDS cases reported through December 1997; Year-end edition. 9: 1-43). ---------------------
14) Disclaimer attached to Merck's HIV protease inhibitor.
"Crixivan is not a cure for HIV or AIDS. People taking Crixivan may still develop infections or other conditions associated with HIV. Because of this, it is very important for you to remain under the care of a doctor. It is not yet known whether taking Crixivan will extend your life or reduce your chances of getting other illnesses associated with HIV. Information about how well the drug works is available from clinical studies up to 24 weeks." -----------------------
15) From the 1997 NIH Guidelines to physicians for the Use of Anti-retroviral Agents in HIV-Infected Adults and Adolescents
"The physician and the patient should be fully aware that therapy of primary HIV infection is based on theoretical considerations, and the potential benefits..., should be weighed against the potential risks."
"[N]o long term clinical benefit of treatment has yet been demonstrated."
Theoretical rationale is fourfold:
� to suppress viral replication
� to potentially decrease the severity of acute disease
� to potentially alter the initial viral "set point," which may ultimately affect the rate of disease progression
� to possibly reduce the rate of viral mutation due to the suppression of viral replication.
Notice the potentiallys, possibly, and may. This theoretical rationale is the basis on which authorities endorse treatment of HIV infection. This is because, aside from the original Fischl et al. AZT clinical trial (which was not confirmed by subsequent trials) (Fischl MA, et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med 317: 185-191 (1987)), no clinical trial has demonstrated that any anti-HIV drug, or combination of drugs, prolongs the lives of HIV positive people, or in general does more good than harm. Short-term changes in surrogate markers are the only bases of FDA approval of anti-HIV drugs. -----------------------
Since the anti-HIV drugs were clearly doing a considerable amount of harm, the NIH finally changed the treatment recommendations. In February 2001, the US National Institutes of Health (NIH) warned doctors to limit the use of anti-HIV drugs and not prescribe them to asymptomatic HIV positive people (Altman L: U.S. Panel seeks Changes in Treatment of AIDS Virus. New York Times 2001;February 4: 16; New York Times: U.S. warns doctors to limit use of anti-HIV drug. New York Times 2001;Jan. 5: XX).
David Rasnick
Competing interests: None declared

HIV drugs fail in children 27 February 2003

David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583
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Re: HIV drugs fail in children

I have scoured the literature for evidence that the anti-HIV drugs actually prolong the lives, or at least improve the quality of the lives, of the children given these drugs. In short: I could not find any support for either possibility.
To begin with, not one study that claims health benefits of anti-HIV drug-treatment included any control groups , i.e. HIV negative children or mothers from similar backgrounds, or HIV positive children followed over time who were not given the drugs.
However, when control groups that did not receive the anti-HIV drugs were included, the devastating toxic and lethal effects of the drugs were manifest. Below are representative examples of the published studies.
The paper by R. E. McKinney et al. entitled "A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease" acknowledges the shortcomings of not using controls [1]:
"Although no control group was available for direct comparison, the improvement in the children in this study closely paralleled the observations in controlled studies of adults receiving zidovudine [AZT]."
That is, in addition to no control groups, this study showed that AZT has similar effects in children as in adults. We have previously documented that AZT accelerates the deaths of those taking that drug compared to HIV positive people who do not take AZT [2]. By inference, the same could be expected for children given AZT.
Further on, the authors state that, "Children treated with zidovudine [AZT] continued to have bacterial and opportunistic infections. The effect of the drug on the frequency of these events could not be assessed because of the lack of control groups."
In other words, AZT did them no good. The lack of control groups is not exceptional but is actually policy. The excuse given for the lack of control groups is that it is unethical to include them. Most people believe that previously approved anti-HIV drugs actually promote health and well-being because of their willful ignorance of the fact that there is no evidence to support that belief.
Finally, in the study of 88 children, "One or more episodes of hematologic toxicity occurred in 54 children (61 percent)-anemia in 23 children (26 percent) and neutropenia in 42 (48 percent)"-all directly caused by AZT.
-----------------------------
Ricardo S. de Souza et al., in their paper entitled "Effect of prenatal zidovudine on disease progression in perinatally HIV-1-infected infants" [3], state that:
"Our results suggest that maternal treatment with [AZT] may influence the course of disease among perinatally infected infants. In this retrospective study, the risk of RPD [rapid progression of disease] was five to six times higher among infants born to [AZT] treated compared with [AZT] untreated mothers."
"After adjusting for prematurity and maternal clinical characteristics, RPD was three times more likely to occur in infants born to [AZT] treated compared with findings in [AZT] untreated mothers."
Moreover, Figure 1 of the paper clearly shows a dose response for the toxic effects of AZT treatment during pregnancy. The earlier the mother began AZT treatment while pregnant, the sooner her HIV positive child got sick and died compared with the HIV positive children born to HIV positive mothers who did not take AZT during pregnancy.
-----------------------------
Then we have L. Kuhn, et al. in their paper entitled "Disease progression and early viral dynamics in human immunodeficiency virus-infected children exposed to zidovudine during prenatal and perinatal periods" [4], saying that:
"Prenatal and perinatal [AZT] exposure were associated with 1.8- fold increased risk of progression to AIDS or death after adjusting simultaneously for all variables associated with disease progression.... Restricting the analysis to children born after April 1994 (date of public release of the results of ACTG 076), [AZT] exposure was associated with 2.5-fold increased risk of progression to AIDS or death after adjusting simultaneously for the same variables."
"Steady improvements in prognosis of [HIV] infected children unexposed to [AZT] were observed in each successive birth cohort, but infected children exposed to [AZT] lagged behind these temporal changes. Our results are from a well-characterized and prospectively followed cohort of US HIV-infected children and are consistent with recent results from the Italian Registry for HIV Infection in Children"-the next reference below.
-----------------------------
The Italian study entitled "Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy" [5] reveals even more of the tragic consequences of treating pregnant women with AZT:
"The probability of developing severe disease at 3 years of life was significantly higher in children born to [AZT+] mothers...than in those born to [AZT-] mothers.... The same pattern was observed for severe immune suppression: the probability of developing severe immune suppression was significantly higher in children born to [AZT+] mothers...than born to [AZT-] mothers.... Finally, survival probability was lower...compared with children born to [AZT-] mothers..."
In short, if a mother takes AZT during pregnancy, her newborn is much more likely to get severely sick and die by age 3 than a newborn whose mother did not take AZT during pregnancy.
-----------------------------
Another example from the literature of pediatric anti-HIV drug studies is the paper by L. L. Lewis et al. entitled "Lamivudine in children with human Immunodeficiency virus infection: A phase I/II study" [6].
Again, there were no control groups in this study. The authors acknowledge that the nucleoside analog reverse transcriptase inhibitors, including the study compound Lamivudine, act as DNA chain terminators. There is no data in the paper showing that the drug does anything good for the children. On the contrary, among 90 children in the study, "11 children had been withdrawn from study for disease progression [in other words, it didn't work for them] and 10 because of possible lamivudine-related toxicity, and 6 had died."
In short, about 1/3 of the children clearly did not benefit from the drug and there was no report of children who benefited other than the lab reports stating that p24 and viral load decreased. Those lab tests were the only positive indicators that the drug did anything desirable from their perspective.
-----------------------------
Another example in the pediatric literature is by M. W. Kline et al., entitled "A randomized comparative trial of Stavudine (d4T) versus zidovudine (ZDV, AZT) in children with human immunodeficiency virus infection" [7].
I quote: "Until recently, zidovudine (ZDV, AZT) was considered the drug of choice for initial therapy of symptomatic HIV-infected children. Unfortunately, therapy with ZDV sometimes is limited by intolerance, toxicity, or HIV disease progression."
In other words, AZT doesn't work. The study showed that Stavudine and AZT were comparable. So, Stavudine is no advance over AZT.
-----------------------------
Another example is by M. W. Kline et al., entitled "A phase I/II evaluation of Stavudine (d4T) in children with human immunodeficiency virus infection" [8].
"Thirty-five of 37 subjects experienced serious clinical adverse events, including infection (33 subjects), lymphadenopathy (19 subjects), hepatosplenomegaly (15 subjects), chills and fever (12 subjects), and development of an AIDS-defining condition (four subjects)."
"Clinical adverse events of lesser severity that were reported by more than 20% of subjects included rhinitis (76%), cough (70%), diarrhea (68%), rash (62%), nausea and vomiting (51%), abdominal pain (43%), anorexia (41%), respiratory disorder (38%), headache (35%), pharyngitis (32%), pruritis (30%), pain (22%), peripheral neurologic symptoms (22%), and nervousness (22%)."
In the last paragraph of the paper, the authors had the temerity to conclude that, "stavudine appears to hold promise for treatment for HIV infection in children. Its pharmacokinetic properties are consistent and predictable, and it appears to be remarkably well- tolerated and safe. Although our study was not designed to assess the drug's efficacy for treatment of HIV infection, preliminary clinical and laboratory evidence of activity was observed."
One can only wonder if the authors were talking about their own results.
-----------------------------
The last incredible example is by P. A. Pizzo et al., entitled "Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection" [9].
The authors studied 21 children. "Transfusion was required in 14 patients because of low levels of hemoglobin. Dose-limiting neutropenia occurred in most patients who received doses of 1.4 mg per kilogram per hour or more."
"The major limitation of the therapy was hematologic toxicity-a decrease in both the hemoglobin concentration and the white-cell count."
"Regardless of the starting dose, nearly all patients had a transient drop in their neutrophil counts within 10 days of the initiation of AZT therapy."
Both anemia and neutropenia are inevitable consequence of AZT poisoning. And just when you thought it couldn't get worse there is this incredible statement:
"In three of the five children who died, evidence of a response to AZT, particularly neurodevelopmental improvement, was present at the time of death."
That is the ultimate example of "the operation was a success but the patient died" clich�.
David rasnick
References
1 McKinney RE, Jr., Maha MA, Connor EM, Feinberg J, Scott GB, Wulfsohn M, McIntosh K, Borkowsky W, Modlin JF, Weintrub P, et al. (1991): A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group. N Engl J Med 324: 1018-25.
2 Duesberg PH, Rasnick D (1998): The AIDS dilemma: drug diseases blamed on a passenger virus. Genetica 104: 85-132.
3 de Souza RS, Gomez-Marin O, Scott GB, Guasti S, O'Sullivan MJ, Oliveira RH, Mitchell CD (2000): Effect of prenatal zidovudine on disease progression in perinatally HIV- 1-infected infants. J Acquir Immune Defic Syndr 24: 154-61.
4 Kuhn L, Abrams EJ, Weedon J, Lambert G, Schoenbaum EE, Nesheim SR, Palumbo P, Vink PE, Bulterys M (2000): Disease progression and early viral dynamics in human immunodeficiency virus-infected children exposed to zidovudine during prenatal and perinatal periods. The Journal of Infectious Diseases 182: 104- 111.
5 de Martino M, et al. (1999): Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy. AIDS 13: 927-933.
6 Lewis LL, Venzon D, Church J, Farley M, Wheeler S, Keller A, Rubin M, Yuen G, Mueller B, Sloas M, Wood L, Balis F, Shearer GM, Brouwers P, Goldsmith J, Pizzo PA (1996): Lamivudine in children with human immunodeficiency virus infection: a phase I/II study. The National Cancer Institute Pediatric Branch-Human Immunodeficiency Virus Working Group. J Infect Dis 174: 16-25.
7 Kline MW, Van Dyke RB, Lindsey JC, Gwynne M, Culnane M, McKinney RE, Jr., Nichols S, Mitchell WG, Yogev R, Hutcheon N (1998): A randomized comparative trial of stavudine (d4T) versus zidovudine (ZDV, AZT) in children with human immunodeficiency virus infection. AIDS Clinical Trials Group 240 Team. Pediatrics 101: 214-20.
8 Kline MW, Dunkle LM, Church JA, Goldsmith JC, Harris AT, Federici ME, Schultze ME, Woods L, Loewen DF, Kaul S, et al. (1995): A phase I/II evaluation of stavudine (d4T) in children with human immunodeficiency virus infection. Pediatrics 96: 247-52.
9 Pizzo PA, Eddy J, Falloon J, Balis FM, Murphy RF, Moss H, Wolters P, Brouwers P, Jarosinski P, Rubin M, et al. (1988): Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection. N Engl J Med 319: 889-96.
Competing interests: � None declared

Non-specific therapeutic effects of protease inhibitors 27 February 2003

Richard G Fiddian-Green,
None
None
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Re: Non-specific therapeutic effects of protease inhibitors

Protease inhibitors inhibit the conversion of xanthine dehydrogenase to xanine oxidase induced by proinflammatory mediators or hypoxia (1). In so doing they prevent the generation of free radical and possibly the degradation of ATP with depletion of ATP stores. ATP stores take 300 days to be repleted de novo rather than adenenylate nucleotides. Dysoxia, be it induced by hypoxia or the uncoupling of oxidative phosphorylation by cytokines, appears to be the principle cause of organ dysfunctions and failures and nosocomial infections in the acutely and possibly even in the chronically ill. Dysoxia is very likely, therefore, to be an important cause of opportunistic infections especially those caused by gut mucosal dusruption.
If protease inhibitors have any therapeutic value in patients with "AIDS" it is likely, therefore, be due to the above mechanisms and not to a specific effect upon HIV or CD4 counts per se. The drugs might even prevent opportunistic infections by means unrelated to HIV and CD4 counts.
1. Homocysteine, ATP degradation and free radical release. Richard G Fiddian-Green bmj.com/cgi/eletters/325/7374/1202#27916, 17 Dec 2002
Competing interests: None declared

comments on debate 27 February 2003

Carl Williams,
layperson affected (not infected) by HIV
Devon, England TQ11 0LQ
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Re: comments on debate

Dear Editor, �
I have followed the debate on various issues regarding HIV as a sexually transmitted disease, the utility of the tests used for diagnosis and the treatment given to those diagnosed HIV positive with interest.� There are several points that have struck me about this debate. �
1)�� I feel that when those involved in an intellectual debate feel the need to personalise the issues by attacking the person, or persons who hold differing opinions to theirs, they do themselves a disservice.
2)�� When participants employ emotive language I feel this is unhelpful to the debate. The discussion is debased by a lack of humility and honesty when those who take part in it feel unable to acknowledge the validity of opposing points that have been made.� This is especially pertinent as participants often put forward research that can be interpreted to support differing opinions.
3)�� In my opinion, when an attempt is made to stifle debate or to censor it, this indicates that the person who initiates such action feels threatened to have their position questioned.� A person who is sure of their own position would feel comfortable to answer questions relating to it without regarding those questions as a threat, or an affront to the �scientific method�.
4)�� When there are many contentious issues it may be that neither side is entirely right, nor entirely wrong - contrary to Brian T Foley�s earlier remark �We obviously both can't be right.� Perhaps the answer may be that both are partly right and partly wrong.��
5)�� I think it is important to acknowledge that regardless of how much research appears to support the orthodox point of view, the sheer quantity of research does not invalidate the significance of supposed discrepancies that do not fit comfortably within the conventional paradigm, neither does it make those who point out research that is seemingly incongruent �in denial�. �
Without intending to denigrate the importance of the points that are being debated, I would like to point out that much of the argument is circular and �tit for tat� responses do not necessarily further the debate.� As has been pointed out it is practicably impossible for David Rasnick to prove his points with the aid of the research that he asserts needs to done, because to do so would involve protocols that are currently considered to be unethical.� Conversely it is impossible for Brian T Foley to prove his points (in the manner that David Rasnick would like) because, regardless of inconsistencies or lack of accuracy with earlier methodologies employed in initial research into the cause of AIDS (as Brian T Foley has himself pointed out), all research since those early days has had the built-in assumption that HIV is a sexually transmitted retrovirus and that once a person has tested HIV antibody positive, their CD4 T + Lymphocyte cells will be gradually eroded by the persistent chronic HIviral infection. �
At the risk of being labelled one of the �less scientifically educated people� that Riccardo Baschetti referred to by offering the following (perhaps naively flawed) suggestion, maybe there is research that could be carried out that would settle this debate, or at the very least a protocol that might help to settle some of the issues without the necessity of recourse to unethical research. �
Given that the central issue of this debate appears to be that one side sees the existence of HIV in AIDS patients as just a correlation, whereas the other side sees the relationship of HIV to AIDS as causative, is it possible to use correlation as the proof for causation?� I imagine that this would be impossible to prove by epidemiological means because if (as David Rasnick has asserted) there are reasons other than the acquisition of an exogenous retrovirus being transmitted in every case that can account for the positive HIV test result, the more people who are tested for HIV the more people will invariably test positive. Thus those who state HIV is exogenous would always see the correlation that supports their theory and those who choose David Rasnick�s interpretation of correlation only would always see the positive results as supporting their theory.� Perhaps one way of showing whether or not the orthodox theory is right would be to test everybody in the world using exactly the same test kit and criteria for a positive result. As that seems unlikely to happen there is a far simpler way of discounting some of the assumptions that are the basis of some dissenting views. �
The orthodox theory is that HIV is a relatively recent co- inhabitant with humans.� The UNAIDS surveillance figures referred to by Tony Floyd, state that the appearance of HIV in various parts of the world began in the 70�s and 80�s, thus supporting the proposition that HIV has a latency period of around ten years before its presence become noticeable in its host. �
As I understand it the so-called �dissident� theories of what HIV is, or isn�t, are varied on this point, but there appears to be one clear distinction between dissident and orthodox theories, and that is that all dissident theories assume that HIV is not a new exogenous retrovirus. Therefore HIV, or at least a positive HIV antibody test, or PCR amplification of �gag�, �env� and �pol� sequences should in principle have been present in much earlier blood sera.� �
My lack of a scientific education may let me down at this point as I don�t know how practically possible this may be to accomplish, but I would suggest that researchers examine stored blood samples from all over the world, from as far back as possible (from people who were in varying degrees of health) and test those samples using the modern test kits that according to Tony Floyd are 100% sensitive and specific (or at least approaching that degree of accuracy), to see what happens.� Of course such testing should be totally blinded with the use of modern day control samples so that no claims can be made that assumptions are built into the outcomes. If there prove to be no positive results from these older samples, then surely the theory that HIV is anything but new would be disproved and conversely if there were positive results then perhaps we should look into why this so and how this effects our understanding of the role of HIV in modern day disease progression.
Yours Carl
Competing interests: � concerned about scientific debate

HIV - from lethal into a chronic infection with drugs 27 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: HIV - from lethal into a chronic infection with drugs

Various authors have been described above as:

"dissidents within the ranks of mainstream AIDS researchers"
One of the authors (reference number 12 in the response 'The anti-HIV drugs') cited is Kees Brinkman, who has authored several papers regarding side effects of anti-HIV drugs. But does he fit the claimed 'dissident' label? A quick search of PubMed reveals quite the opposite. For example, his 2002 Journal of Clinical Virology paper(1) clearly states that:

"With the introduction of HAART, the HIV-1 has turned from a lethal into a chronic infection in the majority of patients."
HAART of course is an acronym for 'Highly Active Antiretroviral Therapy', or the newer breed of anti-HIV drugs.
The author's research into the side effects of those drugs does not seem to have turned him into much of a dissident.

References:
(1) Wolters LM, Niesters HG, Hansen BE, van der Ende ME, Kroon FP, Richter C, Brinkman K, Meenhorst PL, de Man RA. Development of hepatitis B virus resistance for lamivudine in chronic hepatitis B patients co-infected with the human immunodeficiency virus in a Dutch cohort. J Clin Virol 2002 Apr;24(3):173-81

Competing interests: None declared

Do HIV drugs do more harm than good? 28 February 2003

Peter J Flegg,
Physician
Blackpool Victoria Hospital, Blackpool UK, FY3 8NR
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Re: Do HIV drugs do more harm than good?

Response to Rasnick�s letter (The anti HIV drugs, 26th Feb)
No one is denying that anti-HIV drugs have side effects and sometimes serious toxicities. As with all drugs, their use requires a careful risk- benefit assessment. For HIV drugs, the balance is clearly tipped in favour of benefit in treating symptomatic or advanced HIV disease, but not for early, asymptomatic infection. There is still uncertainty as to the benefits with acute (primary) HIV infection (a totally separate clinical concept, the significance of which seems to completely escape Rasnick). He is unable to distinguish the differences between an appropriate expression of concern about drug toxicity potentially outweighing the benefits of therapy in early disease from the unequivocal benefit of using the drugs in progressive HIV infection. I suggest he look at the current guidelines for the use of antiretroviral therapy to find out exactly when their use is advised before he comments further. Just because a doctor states that insulin would be inappropriate to use for someone with mild type 2 diabetes, it does not mean he is recommending it is not given to treat diabetic keto-acidotic coma. In Rasnick�s denialist world, any comment that reflects on HIV drugs as having side effects is assumed to be a ringing endorsement for his claim that they are nothing but poison.
Rasnick states: "It is not surprising that the well-known mechanisms of action and severe toxicities of the anti-HIV drugs have produced dissidents within the ranks of mainstream AIDS researchers. These mainstream dissidents take issue with the claim that the anti-HIV drugs do more good than harm. A list of examples follows:"
It is disingenuous of Rasnick to claim that his list consists of mainstream researchers who are "dissidents" who agree the drugs do more harm than good. In true denialist fashion, he misquotes and reinterprets their findings to suit his own agenda. Not one of these individuals would endorse the denialist position, and some that I know personally would be horrified that Rasnick has twisted their data in such a fashion.
Let us take his examples one by one, seeing if the researchers state that the drugs "do more harm than good".
Rasnick: "1) Seligmann M, et al. Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Lancet 343: 871-881 (1994)). "The results of Concorde do not encourage the early use of zidovudine [AZT] in symptom-free HIV-infected adults. They also call into question the uncritical use of CD4 cell counts as a surrogate endpoint for assessment of benefit from long-term antiretroviral therapy".
Sorry, there is nothing here other than the finding that early use of zidovudine in symptom-free adults did not improve outcome.
Rasnick: "2) Fleming TR Surrogate markers in AIDS and cancer trials. Statistics in Medicine 13: 1423-1435 (1994) In the Concorde Study, there was a 25% higher mortality rate among those who took AZT early compared to those who took the drug later. The pressures to use AZT treatment in asymptomatic persons with HIV were not supported by this and other long-term clinical trials."
In fact Concorde was a rather more complex study than many realise, with different ways of assessing outcome. The HIV-related mortality over the study period of 3 years was higher in those on early compared to deferred zidovudine (81 vs 69, a non significant difference) but mortality over longer term study rose to 241 in the early zidovudine group compared to 199 in the deferred group ( a difference of 21%, not 25%). It is interesting to note that there were fewer events (AIDS/death) in the early versus deferred zidovudine group (162 vs 184). Considering that zidovudine is meant to be extremely "toxic" and "immunosuppressive", this is quite a remarkable statistic.
Rasnick: "3) Jay Levy, UCSF AIDS surrogate markers, is there truth in numbers?, JAMA vol 276, pages 161-162 (1996) Commenting in 1996 on Abbott's report of increased survival in its HIV protease inhibitor clinical trial Levy said: "...can one really report a 50% increase in survival based on only 6 months of treatment and results that reflect 4.8% (treated) vs 8.4% (untreated) of the subjects studied? ...With all the hoopla about antiviral drugs, and you get any virologist aside and they'll say this is not how we are going to win, it's high time we look at the immune system"
Sorry, how exactly does this show the "drugs do more harm than good"?
Rasnick: "Two years later Levy was still unconvinced that the anti- HIV drugs do more good than harm. 4) Jay Levy Caution: should we be treating HIV infection early?, The Lancet 352: 982- 983 (1998). "The clinical state (if the person is without symptoms) is not a major detriment [to administering anti-HIV drugs]: it is the [viral load] numbers that appear to decide the therapeutic course. I take issue with that approach." "[T]hese drugs can be toxic and can be directly detrimental to a natural immune response to HIV... This effective antiviral immune response is characteristic of long-term survivors who...have not been on any therapy. ...[T]he current antiviral therapies...do not bring about the results achieved by a natural host anti-HIV response. This immune response, observed in long-term survivors, maintains control of HIV replication without the need for antiviral treatment."
I have already pointed out to Rasnick in a previous letter that this comment concerns the use of the drugs in early, asymptomatic infection when there is no argument that they would be better left until later on in the course of disease. However in true denialist style, he refuses point blank to take on board data that contradict his belief, in complete perversion of the scientific method.
Rasnick: "5) A. N. Phillips and G. D. Smith, Viral load and combination therapy for human immunodeficiency virus, The New England Journal of Medicine 336, no. 13: 958-959 (1997) "No randomized trials in asymptomatic patients have established that those treated early survive any longer than those for whom treatment is deferred. Extended follow-up of patients in one trial, the Concorde study, has shown a significantly increased risk of death among the patients treated early. The suggestion is that the situation is different for combination therapy. But where is the evidence...?" "There is no more hard evidence now of the benefits of early therapy than there was in 1990. We need new randomized trials to determine whether the notion that was probably not true in the era of [AZT] monotherapy-that early therapy prolongs survival as compared with deferred therapy-is now true."
Again, these authors are commenting on the results of Concorde , reflecting that there is no evidence supporting the use of early zidovudine. Suggestions had been made that combination therapy may prove to be of greater benefit, but Andrew Phillips asks where is the evidence for this, and calls for more studies. If this is what Rasnick claims is a mainstream dissident position, then I must call myself and most colleagues dissidents also, since we all ask for evidence to support hypotheses before accepting them.
Rasnick: "6) Don Abrams, SF General Hospital Tanaka, M. "Abrams cautious on use of new AIDS drugs", Synapse vol 4, pages 1 & 5 (1996) "In contrast with many of my colleagues..., I am not necessarily a cheerleader for anti-retroviral therapy. I have been one of the people who's questioned, from the beginning, whether or not we're really making an impact with HIV drugs and, if we are making an impact, if it's going in the right direction." "I have a large population of people who have chosen not to take any antiretrovirals... They've watched all of their friends go on the antiviral bandwagon and die, so they've chose to remain na�ve [to therapy]. More and more, however, are now succumbing to pressure that protease inhibitors are 'it'... We are in the middle of the honeymoon period, and whether or not this is going to be an enduring marriage is unclear to me at this time..." -
"whether or not this is going to be an enduring marriage is unclear to me at this time.." Perhaps Rasnick should ask Don Abrams what his position is now, 7 years later. Again, I see nothing Abrams says in this interview in 1996 that suggests the drugs cause "more harm than good", only anecdotal evidence from his patients that those who are on the drugs tend to be the ones who die. If Rasnick wants us to use anecdote as evidence instead of controlled trials, I can provide him with plenty of counter examples. Strangely, the patients I see in hospital who die from myocardial infarction all happen to have been given aspirin when they developed chest pain. Should I take this as anecdotal evidence that aspirin has caused their death?
Rasnick: "7) The Italian Register for HIV Infection in Children "Rapid disease progression in HIV-1 perinatally infected children born to mothers receiving zidovudine monotherapy during pregnancy" AIDS 13: 927- 933 (1999) "The probability of developing severe disease at 3 years of life was significantly higher in children born to [AZT+] mothers...than in those born to [AZT-] mothers... . The same pattern was observed for severe immune suppression: the probability of developing severe immune suppression was significantly higher in the children born to [AZT+] mothers... than born to [AZT-] mothers... . Finally, survival probability was lower in children born to [AZT+] mothers...compared with children born to [AZT-] mothers..." In short, if a mother takes AZT during pregnancy, her newborn is much more likely to get severely sick and die by age 3 than a newborn whose mother did not take AZT during pregnancy. --
This study offers no suggestion that zidovudine toxicity is in anyway implicated. Instead, the authors speculate that zidovudine resistance may play a part. This Italian Register has published data on 1142 children with HIV in total, but Rasnick would prefer you didn�t look at this to closely, only the bits he thinks support his case. Why else would he ignore their findings that children who receive triple combination HIV therapy have a 71% lower risk of death than those on no therapy? (ref 1)
Rasnick "8) Amanda Mocroft et al. "Anaemia is an independent predictive marker for clinical prognosis of HIV -infected patients from across Europe" AIDS 13: 943-950 (1999) These authors looked at 6725 patients from EuroSIDA, a prospective study in 52 centers across Europe. They "found a strong relationship between haemoglobin, CD4 lymphocyte count and risk of death."
Hmmm�. And I always thought dissidents said CD4 counts were not a predictor�..
Rasnick: "Their results showed that patients with severe anemia had from 30 to 90 times the risk of death compared to patients with a normal hemoglobin level. There is no mystery to this extraordinarily high risk of mortality since the authors provide the answer themselves: "Patients with mild or severe anaemia were significantly more likely to have taken zidovudine [AZT] at some stage... . In addition, patients with anaemia, mild or severe, were much more likely to have been diagnosed with AIDS..." "We found that 78.2% of the patients with mild or severe anaemia at baseline had received zidovudine [AZT]..." Anemia is listed in the black box warning label as one of the toxic consequences of taking AZT. -
Dissidents always state correlation does not equal causation, but it seems Rasnick is happy to do this when it suits him (the mark of a true scientist!), There is an association between anaemia and mortality, and yes, zidovudine can cause anaemia, but the mortality is unlikely to be explained by zidovudine use alone. In this cohort study, there are several other variables, not least the severity of illness, but you will not find Rasnick mentioning these, obviously.
Perhaps Rasnick would rather study the conclusions that the EuroSIDA Group make concerning antiretroviral therapy in general and outcome/survival:
"Death rates across Europe among patients infected with HIV-1 have been falling since September, 1995, and at the beginning of 1998 were less than a fifth of their previous level. A large proportion of the reduction in mortality could be explained by new treatments or combinations of treatments". (Ref 2)
"Antiretroviral therapy has been used more aggressively in Europe in recent years, resulting in improved prognosis" (Ref 3)
"These results suggest that the beneficial effect of nucleoside combination therapy identified in controlled trials can be seen in routine clinical practice."(Ref 4)
Rasnick: "9) O. A. Olivero et al. "Incorporation of zidovudine into leukocyte DNA from HIV-1- positive adults and pregnant women, and cord blood from infants exposed in utero" AIDS 13: 919-925 (1999) "...further study of the biological consequences of [AZT]-induced DNA damage in the human population is warranted."
Sensible enough, but not evidence that the drugs "do more harm than good".
Rasnick: "10) R. van Leeuwen, et al. "Additive or sequential nucleoside analogue therapy compared with continued zidovudine monotherapy in HIV-infected patients with advanced disease does not prolong survival: an observational study" The Journal of Infectious Diseases 175, 1344-1351 (1997) "Additive or sequential treatment was associated with an increased risk of death."
The reasons for a lack of efficacy with the above strategy are now clear, and relate primarily to the use of inadequate drug regimens and viral resistance. The main reason for the change in drug treatment regimen in these patients was because of side effects from zidovudine, so it is unsurprising that a group of patients pre-selected for analysis because of drug toxicity should also show the possible consequences of this toxicity.
Rasnick: "11) S. Lindb�ck, et al. "Long-term prognosis following zidovudine monotherapy in primary HIV type 1 infections", The Journal of Infectious Diseases 179, 1549-1552 (1999) "Zidovudine treatment initiated during primary HIV (PHIV) infection did not improve long-term outcome after symptomatic PHIV infection."
Again, I suggest Rasnick finds out what "primary HIV infection" actually is, and what current guidelines suggest about use of HIV therapy in this situation. It is unknown if there is likely to be overall benefit, and studies are ongoing. And yet again, this paper does not show the "drugs do more harm than good".
Rasnick: "12) K. Brinkman, et al. "Mitochondrial toxicity induced by nucleoside-analogue reverse- transcriptase inhibitors is a key factor in the pathogenesis of antiretroviral-therapy-related lipodystrophy", The Lancet 354, 1112-1115 (1999) "...nearly all side-effects that have been attributed to the use of NRTIs, such as polyneuropathy, myopathy, cardiomyopathy, pancreatitis, bone- marrow suppression, and lactic acidosis, greatly resemble the spectrum of clinical manifestations seen in inherited mitochrondrial diseases."
Confirmation of toxicity, but not evidence that the "drugs do more harm than good".
Rasnick: "13) Anthony Fauci, Director NIAID, NIH Quoted in "1997 Year of the Crash: Despite New AIDS Drugs, Many Still Lose the Battle" by Sheryl Gay Stolberg, New York Times, Friday, August 22, 1997, Page 1. "'There is an increasing percentage of people in whom, after a period of time, the virus breaks through,' said Dr. Anthony Fauci, director [NIAID]. 'People do quite well for six months, eight months or a year, and after a while, in a significant proportion, the virus starts to come back.'" "No one knows the true extent of the problem, but Fauci estimates that when these cases of 'viral breakthrough' are accounted for, the failure rate of the new drug cocktails may eventually run as high as 50 percent." Fauci's failure rate was really 100% in the AIDS cases that actually have symptoms of disease."
Is Rasnick claiming that 100% of Fauci�s patients have failed to respond to therapy? If he is, a reference to this data would be nice. Fauci appears to be saying here (in 1996) what has been shown to happen, namely that some patients do not have a durable response to therapy. This is not evidence that the "drugs do more harm than good".
Rasnick: "14) Disclaimer attached to Merck's HIV protease inhibitor. "Crixivan is not a cure for HIV or AIDS. People taking Crixivan may still develop infections or other conditions associated with HIV. Because of this, it is very important for you to remain under the care of a doctor. It is not yet known whether taking Crixivan will extend your life or reduce your chances of getting other illnesses associated with HIV. Information about how well the drug works is available from clinical studies up to 24 weeks."
And this is evidence for what exactly? The use of quotes from legal disclaimers on drug packets or laboratory tests has long been used by dissidents as "evidence" of something fishy, but it is never clear exactly what (other than a healthy respect for a legal system that has resulted in disclaimers such as "Warning: May contain nuts!" appearing on packets of nuts).
Rasnick: "15) From the 1997 NIH Guidelines to physicians for the Use of Anti-retroviral Agents in HIV-Infected Adults and Adolescents "The physician and the patient should be fully aware that therapy of primary HIV infection is based on theoretical considerations, and the potential benefits..., should be weighed against the potential risks." "[N]o long term clinical benefit of treatment has yet been demonstrated." Theoretical rationale is fourfold: � to suppress viral replication � to potentially decrease the severity of acute disease � to potentially alter the initial viral "set point," which may ultimately affect the rate of disease progression � to possibly reduce the rate of viral mutation due to the suppression of viral replication. Notice the potentiallys, possibly, and may. This theoretical rationale is the basis on which authorities endorse treatment of HIV infection."
No, No, NO, and NO! This is the basis on which authorities in 1997 considered the use of treatment for primary HIV infection! Again I refer Rasnick to the literature on this subject. Also, this rationale may have been theoretical then, but 6 years on there is evidence emerging from a number of studies that supports it.
Rasnick:"Since the anti-HIV drugs were clearly doing a considerable amount of harm, the NIH finally changed the treatment recommendations. In February 2001, the US National Institutes of Health (NIH) warned doctors to limit the use of anti-HIV drugs and not prescribe them to asymptomatic HIV positive people (Altman L: U.S. Panel seeks Changes in Treatment of AIDS Virus. New York Times 2001;February 4: 16; New York Times: U.S. warns doctors to limit use of anti-HIV drug. New York Times 2001;Jan. 5: XX)."
At long last Rasnick acknowledges that there are guidelines, and that they do not recommend use in asymptomatic patients. But the reasons that the treatment recommendations were changed is not because "the anti-HIV drugs were clearly doing a considerable amount of harm", but because they were not shown to have clear benefits that outweighed the risks. There is a difference.
For those of you who have managed to last this far into the rebuttal of Rasnick�s claims, I too apologise for the length of this letter. Some, like JK Anand (19th February) have stated they wish to see a point by point rebuttal. It is clear from Rasnick�s list of references that he is guilty of: (a) failing to understand the natural history of HIV infection, being unable to distinguish primary from early from advanced infection, and (b) using selective, out of context quotes that do not even then provide evidence for what he claims, namely that the anti-HIV drugs "do more harm than good".
As a list of references that clearly shows evidence for any harm outweighing good, I remain distinctly underwhelmed.
Refs: 1. Italian Register for HIV Infection in Children and the Italian National AIDS Registry. Reduction in Mortality With Availability of Antiretroviral Therapy for Children With Perinatal HIV-1 Infection JAMA. 2000;284:190-197)
2. Mocroft A, et al.Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet 1998 Nov 28;352(9142):1725-30)
3. Chiesi A, et al Regional survival differences across Europe in HIV -positive people: the EuroSIDA study. AIDS 1999 Nov 12;13(16):2281-8
4. Phillips AN et al. Survival in 2367 zidovudine-treated patients according to use of other nucleoside analogue drugs. The EuroSIDA Study Group. J Acquir Immune Defic Syndr Hum Retrovirol 1998 Mar 1;17(3):239-44
Competing interests: Attendance at HIV conferences under sponsorship from Glaxo Smith Kline, Bristol Myers Squibb, Gilead, Abbott, Boehringer Ingleheim and Merck.

Another round of reference checking reveals more holes in AIDS-Denialist argument 28 February 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Another round of reference checking reveals more holes in AIDS-Denialist argument

Yet another one of the authors cited above as an 'AIDS dissident' has published work contrary to that label and, whilst aware of the side effects, supports the use of anti-HIV drugs.
Rick van Leeuwen (reference number 10 in the response 'The anti-HIV drugs') was also listed as a researcher that believed that anti-HIV drugs do more harm than good. Checking the actual Journal of Infectious Diseases(1) article cited above reveals that the HIV-infected patients studied were already at an advanced disease state when treatment was changed. It does not suggest that they would have been better off without drugs all together.

References:
(1) van Leeuwen R, Bonsel GJ, Reiss P, Danner SA, Lange JM. Additive or sequential nucleoside analogue therapy compared with continued zidovudine monotherapy in human immunodeficiency virus-infected patients with advanced disease does not prolong survival: an observational study. J Infect Dis 1997 Jun;175(6):1344-51
Competing interests: None declared

Re: comments on debate 1 March 2003

Peter Morrell,
freelance researcher, history of medicine, UK
Staffordshire, UK
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Re: Re: comments on debate

Sir,
I find myself in complete agreement with Carl Williams� very sensible letter and its many erudite comments about this enriching and fascinating debate. However, I would like to add some points of my own.
The deeper implications of what Rasnick is saying need to be considered a little more carefully. For example, if HIV is not the cause of Aids, then what is? If HIV is not the cause of Aids, then what is HIV all about and what type of association, if any, does it have with Aids as a syndrome? Further, if HIV is not sexually transmitted, then how is Aids acquired and passed on in heterosexual populations like Africa? Questions such as these all flow naturally from the position that Rasnick has presented. Thusfar, none of his critics has taken his case seriously enough and considered these implications deeply, being far too eager to emotionally reject his views outright and attack him as a person. As Williams clearly states, they greatly weaken their own arguments by such uncharitable and disrespectful behaviour.
Looked at conceptually, what we see here is a group of people very eager indeed to believe that HIV causes a condition called Aids and that it is sexually transmitted; they reach for the virus hypothesis as if by reflex, and become very angry when others question or dismiss this theory as somehow deficient or bogus. Two elements emerge in that scenario - why are they so averse to criticism of the orthodox theory? And why are they so angry? As 'neutral and emotionally detached scientists' [so-called] they should be eager and willing to discuss alternatives and to take on board any critique of their views without any emotional interference. That would be a best-case scenario of the decent scientist as �neutral observer.�
Rasnick�s critics have all fallen a long way short of that ideal and reveal themselves NOT as emotionally neutral disinterested parties or truly objective minds in this matter, but indeed, emotionally biased and quite outraged that someone dares to challenge the orthodox theory. Their very emotionality reveals that their views are rooted more in belief than in evidence. As Williams also states, a person who is calm and firm in their view based in evidence, does not need to get angry with those who oppose his views.
Rasnick has behaved throughout this debate with impeccable calm and rationality, in spite of repeated personal attacks. This stands in very marked contrast to the openly vicious comments made about him by his critics. You only have to read their letters besmirching Rasnick as a dissident, an Aids denialist and a non-scientist - the regrettable language they use reveals a fundamental fear and insecurity on their part, the basis of which needs to be more clearly established.
They have turned a rational discussion into a witch-hunt. They have demonised Rasnick and his viewpoint. They would probably even go so far as to say he does not have the right to express that view. What seems genuinely worrying, viewed from the sidelines, is that these guys present themselves as scientists and yet their behaviour is more like some fundamentalist Christian, or worse. Who is going to believe such people in preference to calmly reasoned argument?
There is a more general need to explore why clinicians want to adhere to the virus theory [any virus theory] and how generally convenient that idea has become to the modern medical mindset. For example, it might be possible, and often is in the natural world, that two things become correlated without being causally connected. Could not sexual transmission, HIV and Aids have become accidentally entangled at an early stage and their non-causal association been interpreted too literally from the start as a definite causal relationship, which workers have subsequently been too unwilling to question? If so, then Rasnick makes a very important point.
The argument in large part revolves about adherence to an orthodox view and defence of a status quo of belief, plus posturing to medical conformity and the hidden agenda of vested interest, all couched in the language of repelling a dissident as if they signal the approach of some pernicious evil. This has very little to do with science and a lot to do with a social process and the release of pent-up emotions covertly concerning financial self-interest and drug company endorsements, careers at stake, and belief in science as a religious condition in the modern world. As manifested by this discussion, that mental condition is every bit as passionately dogmatic, as narrowly blind, as all-consuming, as fanatical as the rantings of any truth-hating medieval cleric, cardinal or bishop.
Modern medicine seems a tad too eager to accept the preferred and simplistic disease causes such as gene and virus, rather than admit the less convenient social, lifestyle, dietary or socio-economic causes of human sickness. Moreover, this molecular and reductionist fixation blinds it to the importance of such causes. Are clinicians still deaf to the valid points of McKeown and Illich made forty years ago?
Competing interests: None declared

Time to Try and See the Forest Inspite of the Trees. Checking Common References. 1 March 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Time to Try and See the Forest Inspite of the Trees. Checking Common References.

As Carl Williams response ('comments on debate' 27th Feb) rightly points out, this (alleged) debate appears to be going nowhere.
As the goal posts continue to be shifted, those who haven't yet fallen asleep could check references used by more than one author and make their own mind up.
Both David Rasnick and Peter Flegg have cited:
M Seligmann, whose 19 99 Lancet article(1) states:

"Subcutaneous interleukin-2 is a convenient regimen that, as well as intravenous therapy, improves immunological function in HIV-1-infected patients receiving two nucleosides. Larger studies are needed to show whether immunological improvements translate into clinical benefit."
Seligmann hence studied whether or not interleukin-2 augments the treatment of patients receiving 2 anti-HIV drugs. Odd he would do such a thing if he thought the drugs were no good at all.

TR Fleming, whose 199 5 article(2) discusses statistical challenges and opportunities in HIV vaccine trial design. Any suggestion that either vaccines or existing drugs are a waste of time is notably absent.
AN Phillips, whose 20 02 article(3) states:

"Although studies have reported large reductions in the risks of AIDS and death since the introduction of potent anti-retroviral therapies, few have evaluated whether this has been similar for all AIDS-defining diseases."
Which I interpret to mean that the drugs reduce death, but the authors would like to compare the benefit amongst particular diseases. Checking the evidence reveals that Phillips, like other authors cited, reaffirms the efficacy of anti-HIV drugs.

*** References:
(1) Levy Y, Capitant C, Houhou S, Carriere I, Viard JP, Goujard C, Gastaut JA, Oksenhendler E, Boumsell L, Gomard E, Rabian C, Weiss L, Guillet JG, Delfraissy JF, Aboulker JP, Seligmann M. Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. ANRS 048 study group. La ncet 1999 Jun 5;353(9168):1923-9
(2)Schaper C, Fleming TR, Self SG, Rida WN. Statistical issues in the design of HIV vaccine trials. Ann u Rev Public Health 1995;16:1-22
(3) Babiker A, Darbyshire J, Pezzotti P, Porter K, Rezza G, Walker SA, Beral V, Coutinho R, Del Amo J, Gill N, Lee C, Meyer L, Tyrer F, Dabis F, Thiebaut R, Lawson-Aye S, Boufassa F, Hamouda O, Fischer K, Pezzotti P, Rezza G, Touloumi G, Hatzakis A, Karafoulidou A, Katsarou O, Brettle R, del Romero J, Prins M, van Benthem B, Kirk O, Pederson C, Hernandez Aguado I, Perez-Hoyos S, Eskild A, Bruun JN, Sannes M, Sabin C, Lee C, Johnson AM, Phillips AN, Francioli P, Vanhems P, Egger M, Rickenbach M, Cooper D, Kaldor J, Ashton L, Vizzard J, Muga R, Day NE, De Angelis D; CASCADE Collaboration. Changes over calendar time in the risk of specific first AIDS-defining events following HIV seroconversion, adjusting for competing risks Int J Epidemiol 2002 Oct;31(5):951-8
Competing interests: Students are encouraged to check references and find such flaws.

Re: comments on debate 2 March 2003

Christian Fiala,
Specialist in OB/Gyne
Vienna, Austria
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Re: Re: comments on debate

Dear Editor,
spread of HIV in the general population outside so-called risk groups is accepted by many scientists. This conviction is based on the information given by patients on their own sexual preference after they got a positive HIV-test or an Aids-diagnosis. Although we know that information given about ones own sexual life and preference or ones (illegal) drug use is by no means reliable nor can it be proven. It is therefore necessary to analyse screening programs with a high number of individuals. After two decades of an HIV epidemic, these data should give a reliable answer to the question whether or nor HIV is spreading in the heterosexual population.
Results of the following studies are presented:
1. Anonymous unlinked testing of blood from the umbilical cord
2. Blood donors in Germany
3. Military conscripts in Austria
4. Prostitutes in Europe
5. Thailand (STD's and HIV)
6. Back-calculation of HIV-incidence in Germany
7. Condoms sold in Germany
ad 1. anonymous unlinked testing of blood from the umbilical cord In order to assess the risk for women in the general population, we can rely on the anonymous, unlinked testing of blood from the umbilical cord. The results provide information on the presence of HIV-antibodies in the mother. Since 1993, this survey has been carried out in almost all women giving birth in Berlin, the German city with the most Aids cases per capita, the highest number of i.v. drug adicts and many people from Africa. If transmission of HIV would take place, originating from the so-called risk groups and spreading into the general population than one would expect an increase over the years and a high prevalence after more than 15 years of spread. The same survey is being performed in Lower Saxony and Bavaria. The population in these regions are thought to be of lower risk, based on the prevalence of Aids-cases and people with HIV-anitbodies. In Berlin 0,57 per 1.000 women were HIV-positive, compared to 0,14 in Lower Saxony and 0,16 in Bavaria. The prevalence remained stable over the years not even increasing in Berlin. The Robert Koch Institute in Berlin, which is responsible for the evaluation of the German figures, has come to the following conclusion: "The results - HIV prevalence significantly under one per thousand among women giving birth - confirm the assumption of a low distribution of HIV in the general heterosexual population so far... The observed low prevalence might be an overestimate of the true prevalence due to the fact that a high percentage of the HIV-positive women in this study (60%) come from a Pattern II country."
Robert Koch Institut, Berlin, Bericht zur epidemiologischen Situation in der Bundesrepublik Deutschland. 31.12.1996 Robert Koch Institut, Berlin, Bericht zur epidemiologischen Situation in der Bundesrepublik Deutschland. 31.12.1997 Dathe O. et al, Ist Anonymes Unverkn�pftes Testen auf Anti-HIV an Geb�renden zur Pr�valenzbestimmung sinnvoll?, 6. Deutscher Aids-Kongre�, 1996; P 112
ad 2. blood donors
"Blood donors are representative for the sexual active population.... Analysing this group can therefore give reliable information on the spread of sexually transmissible diseases in the general population after excluding recognisable members of the risk groups." If HIV would spread in the general population this would result in an increasing percentage of HIV-positive blood donors without any risk behaviour in their history. It would also result in a high number of HIV-positive donors after more than 15 years of spread of HIV. There are about 3 million blood donations per year in Germany. The results however show a decline from 9,8 HIV-positive donations per 100.000 in 1985 to 1,4 in 1988 and a constant rate since than, around 0,9-2,4. Leading to the following conclusion: "The data of this study confirm the results of other studies showing a low transmission of HIV outside the well known risk groups." One would need to ad: An effect of the prevention campaigns can not be observed as the described decline took place before they started. All qotations from: Aids-Zentrum im Bundesgesundheitsamt, Bericht zur epidemiologischen Situation in der BRD zum 31.12.1995, Berlin
ad 3. military conscripts in Austria When it comes to the assessment of young people, we can rely on the analysis of HIV tests for conscripts in the Austrian army. Austria is the only western country with an obligatory military service and a screening for HIV of its conscripts. The results have a high validity as about three quarters of the male age-class of 19-21 years is screened in this programme every year since 1985. True, the HIV test is not part of the call-up in Austria. However, practically all of the 40,000 annual conscripts out of a population of eight millions, are regularly tested for HIV, and this goes back to 1985. The basis for this is an agreement between the army, which is seeking a cost-effective method of determining the blood group of its soldiers, and the Red Cross, which exceptionally is prepared to determine the blood group of non-donors at no cost if it is guaranteed that the majority of conscripts take part in the blood-donor scheme. In order to ensure the motivation of the conscripts for this scheme, they are allowed to leave for the weekend on the Friday once they have donated blood. Non-donors, however, including occasionally those who are refused on medical grounds, have to wait until Saturday evening for their weekend leave, and usually no longer have any chance of travelling home by public transport. This procedure, which has been rejected in other European countries as being involuntary, has thus far ensured the almost total testing of Austrian conscripts. As a result, there is now data on the frequency of HIV infection in three quarters of all males aged 19 to 21 for the last twelve years. Actually, it turns out as an average of 2.3 positive results per year. Almost all cases, 25 of the total of 27, came from the Vienna blood bank, which also covers Lower Austria and Burgenland. (Vienna is the only big city in Austria.) In Carinthia, since 1985 there has been a total of two HIV-positive blood donors from army barracks. Since the survey began, in 1985, there has not been one single HIV-positive blood donor from army barracks in the other provinces, Upper Austria, Styria, Tyrol and Vorarlberg. Assuming a participation of about 95% of conscripts in the blood-donor scheme, this results in a rate of six positive HIV tests per 100,000 blood donors. (For all male first-time donors in Germany in 1993, the rate was 11.6). The studies published by the German and the French Ministry of Defence also show a similar result. The data there, however, are not so reliable, because conscripts' participation in the blood-donor scheme was significantly lower because it was voluntary. The spread of HIV among young males outside those involved in the recognised classical risk behaviour cannot be observed on the basis of available data. Nor has there been a change in time demonstrating any spread or effect of the prevention campaigns. Fiala, HIV/AIDS - Wie gro� ist die Gefahr f�r Jugendliche - Am Beispiel der Rekruten, �sterreichisches Institut f�r
Jugendforschung, facts 04/1998
ad 4 prostitutes in Europe Prostitutes are at special risk when it comes to STDs. Consequently one would expect a high prevalence of HIV-positive results in this population. Interestingly a study among prostitutes in Europe found an HIV-prevalence of 5,3%. But most of the positive results came from prostitutes admitting i.v. drug consumption (prevalence of 32% compared to 1,5% among the non-drug consuming prostitutes). This is confirmed by the routine screening among the 800 prostitutes in Vienna (1,5 Mio inhabitants.) Since 1985 a total of three of them was found to be HIV-positive. Again this is incompatible with HIV spreading as a STD among the heterosexual population nor can any effect of the prevention campaigns be demonstrated.
Kunz, Virusepidemiologische Information, 1987-97, Wien European Working Group on HIV Infection in Female Prostitutes; HIV infection in European female sex workers: epidemiological link with use of petroleum-based lubricants, AIDS, 1993; Mar; 7(3): 4.1-8
ad 5 Thailand (STD's and HIV no correlation) It is widely believed that HIV spreads mainly by heterosexual means. It is also widely believed that the high prevalence of STDs facilitates the transmission of HIV. It is therefore interesting to analyse some data from a country with a well documented high prevalence of STDs like Thailand: - Prevalence of HIV among STD patients The prevalence of STDs has been very high since decades. Nevertheless the HIV-epidemic is said to have started only around 1990, many years after its introduction into Thailand and 10 years later than in the US. It is difficult to understand why HIV should have started to spread heterosexually only when STD rates where on a sharp decline. - Geographical distribution of STDs and HIV/Aids The highest prevalence of STDs is generally found in great cities. This is also true in Thailand, with Bangkok on the lead compared to other regions in the country. Nevertheless there is no correlation to the HIV-prevalence and the number of Aids-cases. Both of them are highest in the North also known as part of the Golden Triangle and one of the biggest opium producer in the world. But STD prevalence is second lowest in this region. And even if one looks into more detail at the provinces of the North Region one is confronted by the fact that there is absolutely no correlation between STDs and AIDS. With Payo Province having the highest STD-prevalence and the lowest number of cumulative Aids-cases in the North or on the other hand Lamphun Province with the highest number of cumulative Aids cases and a STD-prevalence below average. Again whatever might be the cause of HIV-positive tests in Thailand it can not be heterosexually transmitted like the other STDs.
Chitwarakorn A. et al, Sexually Transmitted Diseases in Asia and the Pacific, 1998, Ministry of Public Health, AIDS Division, HIV/AIDS Situation in Thailand October 31, 1998 Office of Communicable Disease Control Region 10, Chiang Mai, Thailand
ad 6 Back-calculation of the HIV-incidence in Germany The most reliable figure we have in Europe, is the Aids incidence. Even if one has to take into consideration the extension of the definition of Aids at several occasions, leading to an (artificial) increase in the number of Aids-patients. The number of new Aids-cases in Germany grew from 1985 until it peaked in 1993, when the latest modification of the Aids-definition was introduced. It declined since than. The Aids-incidence has been the starting point for the European Institute of Monitoring HIV/Aids, to calculate the HIV-incidence. This back-calculation was based on the assumption of a transmission of HIV leading to Aids after an incubation period of 10 years in average. The result shows a steep increase of new HIV-infections from 1979 to a peak in 1983 at around 7.000, followed by a sharp decline until 1987. The number of new HIV-infections per year is said to be stable at around 2.000 since than. It is remarkable that the so-called HIV-epidemic appears to be self-limited at a very low level. The peak of HIV-incidence from 1983 to 1987 happened long before any intervention (prevention-campaigns) started. Furthermore a low number of number of new HIV-infections is incompatible with an infectious disease in the general population.
Robert Koch Institut, Berlin, Bericht zur epidemiologischen Situation in der Bundesrepublik Deutschland. 31.12.1997 Dietz K., Seydel J., Back-Projection of German Aids data using information on dates of tests, Stat-med , 1991; 13: 1991-2008 Downs A et al, Reconstruction and prediction of the HIV/Aids epidemic among adults in the European Union and in the low prevalence countries of central and eastern Europe, Aids, 1997; 11: 649-62
ad 7 condoms sold in Germany Condom promotion campaigns are part of the so-called prevention campaigns. Analysing the number of condoms sold in Germany can give some information as to the success of changing the sexual behaviour of a population. The number of condoms sold per capita was two condoms in 1980. Fifteen years later it has been 2,3 after numerous campaigns. Apparently most people in Germany don't like condoms and cannot be convinced to use them. A similar situation occurred in Austria, where the number of condoms did not move even during the last campaign in 1994. This has been one of the arguments to stop these campaigns. We know from Family Planning Programs that it is possible to change the contraceptive behaviour to a small extend. But this needs a message that is not only credible but also applicable. But the messages of the condom campaigns in the HIV-area did not correspond with the experiences of the people and proved to be wrong anyway (the epidemic did not happen). But more important the request of using a condom in all circumstances outside a mutually faithful relation, were perceived as being unrealisable and incompatible with a spontaneous sexual life. It is noteworthy that there has been no HIV-epidemic in Germany although condom use remained very low. The population in some other countries might behave more rational in their sexual life than Germans and might use more condoms. Whether this would have an effect on the HIV-prevalence remains to seen.
Mitteilung der Deutschen Latex Forschung, D�sseldorf Mitteilung des Statistischen Bundesamtes Wiesbaden
Conclusion: Heterosexual spread of HIV in the general population cannot be observed where reliable data exist as in the case of Germany. The prevention campaigns have therefore been a waste of money and energy. Furthermore they did not lead to a substantial increase of condom use, but had a negative impact on the credibility of the institutions involved. (The danger, HIV concerns everybody, and the predictions were wrong.) The loss of credibility might have a negative longterm effect for any health education in the future. Countries with a limited budget might set priorities in a different way and invest i.e. in prevention of unwanted pregnancies, avoiding unsafe injections, reducing infectious diseases etc.
Competing interests: � None declared

Hooray! I am part of a conspiracy!!! 2 March 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Hooray! I am part of a conspiracy!!!

I am not sure if any of these comments were directed at myself, but as I haven't taken my medication today I will just assume so and respond anyway:
> if HIV is not sexually transmitted, then how is Aids acquired and passed on in heterosexual populations like Africa?
Low transmissibility (via peni-vaginal sex) of HIV has been demonstrated by numerous studies in countries such as the US. Aside from poorer countries having a much greater prevalence of other STD's (hence creating breaks in the mucosa through which HIV may pass), they were not afforded the same mass-media warnings that increased condom use and decreased peni-anal sex in wealthy countries.

"The increase in HIV infection and transmission in HSV positive patients leads to treat genital ulcers to decline the rate of HIV and HSV transmission. "(1)
Hence those with access to treatments for sexually transmitted infections like herpes decrease their risk of contracting other infections such as HIV.
> reject his views outright and attack him as a person.
Mea culpa. I apologise if I have attacked the person rather than the person's argument. I have seen much emotion on this issue elsewhere; some Doctors became quite upset when babies in South Africa were denied anti-HIV drugs for no good reason. I have provided numerous links above to articles cited by people of differing views, and to other research articles by authors also cited by Rasnick, Flegg and Foley. Follow the links and make your own conclusions as to who is misinterpreting evidence.
> adherence to an orthodox view ... the hidden agenda of vested interest ... pent-up emotions covertly concerning financial self-interest and drug company endorsements
A conspiracy theory!? Fantastic! Hidden agendas, drug companies, JFK's real killer, area 51, say no more! Whilst Peter Flegg and Brian Foley have spent their time providing well-referenced facts that HIV treatments save lives and that sex transmits HIV, would not an ad hominem implication that they are part of a 'conspiracy' be an attack on the person?
If the desire to be sceptical and check the facts makes me part of a conspiracy, then where do I sign for a life membership?

***

References:
(1) Picard O. [Herpetic infections and human immunodeficiency virus] [Article in French] Pathol Biol (Paris) 20 02 Aug;50(7):460-2

Competing interests: Just warming up.

HIV/AIDS - there is no "debate" 3 March 2003

Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital, Blackpool, UK FY3 8NR
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Re: HIV/AIDS - there is no "debate"

Peter Morrell has commented on the "debate", with several accusations of his own concerning those responding to David Rasnick. Seemingly we have resorted to personal attacks, among other things "besmirching Rasnick as a dissident, an Aids denialist and a non-scientist" (http://bmj.com/cgi/eletters/326/7381/126/e#30058). Since Rasnick is a self-confessed dissident and denialist, I fail to see why pointing this out would "besmirch" him. I have not accused him of being a non-scientist, but did refer to him as a dissident "scientist" in an earlier letter. I apologise if this has given the impression that I think he is not (which he clearly is).
Some may feel this "debate" has overheated. For those unfamiliar with it, it must be said that what is visible in this forum represents only a minor fragment. The "acceptable face" of dissidence that Rasnick represents here is not the norm. Orthodox scientists in the pursuit of a cure for AIDS have suffered accusations of genocide and comparisons with Hitler. Those who believe that HIV does not exist have dissuaded HIV- infected individuals from taking therapy and mothers of accepting interventions to prevent their children becoming infected (1,2). A small core of activists patrols the internet, forcing HIV/AIDS information and discussion boards to close, denying those anxious about their status to seek help and advice, or "mail bombing" worried posters with disinformation about HIV. On a larger scale, HIV dissidents like Rasnick and members of Mbeki's Presidential Advisory Panel have helped persuade Mbeki that HIV is not the cause of the AIDS epidemic in South Africa. The human consequences of this have been catastrophic, with up to 40 thousand infants needlessly becoming infected each year with HIV from the lack of drugs to prevent mother to child transmission.
Despite what Rasnick asserts, the Presidential AIDS panel seems to be defunct. As politically expedient as it might have seemed initially for President Mbeki to blame South Africa's health problems on malnutrition, TB and the apartheid legacy, it does now seem that he is being forced to face the realities of his country's HIV epidemic through a combination of the efforts of his own people and the High Courts.
There is no "HIV debate". HIV has been shown to exist and to cause immunodeficiency and AIDS. Ample evidence has been presented for this (3,4) and over 5000 scientists at the Durban International AIDS conference signed up to a "Durban Declaration" to this effect and to refute the disidents' claims.
What is taking place on this forum is a farce, not a debate. A debate consists of two parties discussing evidence for and against a contentious position, with the aim of reaching some definitive conclusion or consensus. Dissidents like to refer to these interchanges as "scientific debate" since this lends veracity to their contention that there is uncertainty about HIV, and their web sites are full of highlighted references to their eBMJ missives, designed to impress casual browsers that they have peer-reviewed publications on the subject. Rasnick has used the opportunity provided by the BMJ to introduce topics far removed from the original article in question. He has moved from sexual transmission to HIV testing, from HIV therapy to paediatric HIV, and there is the veiled promise of more topics to come. Whenever his claims are discounted, or a point by point rebuttal is given, instead of staying "on topic" and discussing these, he moves in a different direction. Good scientists are meant to accept new evidence and incorporate this into their hypotheses. The dissident approach is to ignore new evidence that is contradictory to their predetermined stance. After comprehensive rebuttal of any point of view, the dissident tactic is to quickly switch to a different topic. Then later, when no-one is looking, they can switch back to the original theme, hoping no-one will realise that these points were completely discredited on an earlier occasion.
No-one is denying dissidents the right to express opinions or the opportunity for relevant debate. But as we have seen, even forums like this where there is an opportunity for sensible discussion of evidence, it is very hard to hit a rapidly-moving target. I am saddened that some correspondents do not look a bit deeper into the consequences that arise from the dissident agenda and the real impact this has had from an individual perspective up to national standpoint. I am not concerned about upsetting personal sensibilities when so much is at stake. We are discussing crucial issues here which are relevant to the lives of thousands of people, not semantics about whether the earth is flat.
(1)Edelman K, Horning P, Catalan J, Gazzard B. HIV does not cause AIDS--impact of T.V. programme on attitudes to zidovudine in HIV patients. VIIth Int Conf on AIDS, (abstract no. W.B.2097), June 16-21, 1991
(2)Boyer PJ, Dillon M, Navaie M, Deveikis A, et al. Factors predictive of maternal-fetal transmission of HIV-1. Preliminary analysis of zidovudine given during pregnancy and/or delivery. JAMA 1994;271(24):1925-30
(3) http://www.niaid.nih.gov/newsroom/focuson/hiv00/default.htm
(4) http://www.niaid.nih.gov/publications/hivaids/hivaids.htm
Competing interests: None declared

Heterosexual transmission and credibility 3 March 2003

Christian Fiala,
Specialist in OB/Gyne
1060 Vienna/Austria
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Re: Heterosexual transmission and credibility

Dear Editor,
"Hence those with access to treatments for sexually transmitted infections like herpes decrease their risk of contracting other infections such as HIV" This is a widely held theory repeated by Tony Floyd. Unfortunately things are not as easy: "We observed no effect of the STD intervention on the incidence of HIV-1 infection." Are the conclusions of a study perforemed in Uganda adding to the evidence that HIV is not behaving like an STD. (1)
We do not necessarily need to accept all the contradictions in the theory of heterosexual transmission of HIV. But predictions based on this assumption did not come true in the past and there is no reason to believe they will do so in the future.
What is at stake is credibility. Take the example of Uganda. This country has been subject to dire predictions some 10-15 years ago. The current situation is in sharp contrast to them. Population growth has virtually exploded during the last 10 years from 2.5% to 3,4%. In other words the former epicentre of the Aids pandemic has one of the highest population growths in the world. This is not exactly the result one would expect from a deadly heterosexually transmitted disease.
1.) Control of sexually transmitted diseases for AIDS prevention in Uganda: a randomised community trial. Rakai Project Study Group. Lancet 1999 Feb 13;353(9152):525-35 2.) Uganda Bureau of Statistics, Entebbe: www.ubos.org
Competing interests: � None declared

Re: Do not be seduced by the sirens of dissidence 3 March 2003

Rodney M Richards,
Independent AIDS Researcher
Louisville CO, 80027
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Re: Re: Do not be seduced by the sirens of dissidence

*Practicing in different worlds, the two groups of scientists see different things when they look from the same point in the same direction. ... Each group uses its own paradigm to argue in that paradigm's defense...the status of the circular argument is only that of persuasion. It cannot be made logically or even probabilistically compelling for those who refuse to step into the circle.* (Thomas Kuhn. The Structure of Scientific Revolutions, 1962.)
Peter J Flegg suggests that David Rasnick's critique of problems with the HIV tests (HIV antibody test is the Achilles heel of AIDS, Inc.) is lacking credibility because he relies on "quotes [from] several sources, most of which are either not peer-reviewed or which are so old as to have been superceded by new data (of which he is no doubt aware but prepared to ignore)."
I would like to suggest that information taken from package inserts for diagnostic testing products represents perfectly valid reference material for scientific inquiry and discourse. Even though this information is not formally "peer-reviewed," it is thoroughly reviewed by panels of experts in the field of HIV testing at the United States Food and Drug Administration (FDA) prior to product release, and it is certainly not "old."
Flegg attempts to discount the information Dr. Rasnick quotes from these package inserts by asserting: "Virtually every diagnostic assay will have a legal disclaimer of some sort specifying that the tests should not be the sole basis on which a disease is diagnosed." While it is true that manufactures tend to disclaim their products with regard to the "intended use," they have no liability associated with physicians who choose to use their products "off label" for other purposes. Relevant to this is the little known fact that none of the 30 so-called HIV tests currently approved by the FDA (1) claim to be intended for use in diagnosing infection with HIV in the first place. As such, the notion that statements pertaining to the use of these tests for diagnosing infection with HIV might be cautiously vague or understated due to liability considerations is without merit.
The inappropriate use of antibody tests for the purpose of diagnosing infection with HIV can be traced back to 1987, when the US Centers for Disease Control (CDC) declared: "The presence of antibody indicates current infection." (2) Interestingly, the CDC has never offered any reference to any scientific study to substantiate this claim. Indeed, a substantial proportion (and in some studies the majority) of antibody positive individuals have no evidence of infection whatsoever when their tissues are subjected to the accepted gold standard of HIV culture analysis, which in principle can detect a single infectious viral particle. Nevertheless, the above uncorroborated proclamation from the CDC was quickly accepted as fact and has formed the foundation of all subsequent diagnoses of HIV infection; including the most recent UNAIDS/WHO estimates of 40 million current global infections and 25 million cumulative AIDS deaths. (3)
This is particularly disturbing when one considers that the manufacturers and the FDA explicitly warn against the use of these tests for diagnosing infection. In fact, in the very same year that the CDC endorsed the use of antibody tests for diagnosing infection (1987), the FDA announced, "The significance of antibodies [to HIV] in an asymptomatic individual is not known." (4) Furthermore, according to manufacturers of ELISA tests currently on the market, "The risk of an asymptomatic person with a repeatedly reactive serum sample developing AIDS or an AIDS related condition is not known." (5,6) And even the manufacturers of the so-called confirmatory Western Blot [WB] assays currently on the market, caution, "The clinical implications of antibodies to HIV-1 in an asymptomatic person are not known." (7)
In fact, according to the manufacturers, one should be cautious using these tests even for the purpose of diagnosing antibodies to HIV, let alone infection. According to the manufacturer of the most widely used ELISA, "At present there is no recognized standard for establishing the presence and absence of HIV-1 antibody in human blood." (5) And even the manufactures of WB assays, which supposedly confirm the presence of antibodies (not HIV), inform us that, "A sample that is reactive in both the EIA [ELISA] screening test and the Western blot is *presumed* to be positive for *antibody* to HIV-1." (8) (*emphasis* added)
Well aware of the fact that these tests will ultimately be used to tell people they are infected, the manufactures do warn, "A person who has antibodies to HIV-1 is *presumed* to be infected with the virus." (5,6,8) (*emphasis* added) However, the manufactures themselves will only go so far as to declare, "A positive result *may* indicate infection with [HIV]." (7,8) (*emphasis* added) And this statement pertains to samples that have been "confirmed" positive by WB testing! One could equally well declare, "a positive result for antibodies to herpes simplex virus *may* indicate infection with HIV."
All of this is further complicated by the fact that various institutions and countries use different definitions of what combination of antibody test results should be considered sufficient to hand out declarations of infection. Some countries consider a single ELISA sufficient, while others might require two or three different ELISA tests. Yet other countries or institutions insist their unsubstantiated declarations of infection be based on follow-up WB testing; and even in this case, currently used rules (interpretive criteria, or evaluation criteria) for deciding what combination of bands constitutes a positive result on WB vary dramatically. Consider a person with the following common WB banding pattern: (p24 + gp160). Should this person be told they are infected? According to the criteria of Australia, France, the UK, and the WHO, the answer is, "no." In contrast, according to the criteria of the Germany, the CDC, the Ugandan Viral Research Institute, and the National Institute of Virology (NIV) in South Africa, the answer is unequivocally, "yes!"
Flegg asserts such discrepancies in WB interpretation represent "historical inconsistencies." It is true that various institutions have changed their interpretive criteria over the years, however, as illustrated above, it is not true that the discrepancies have disappeared. Institutions within the USA appear to be closing in on a consensus as to what constitutes a positive WB, however, the USA represents only about 2.5% of the currently estimated 40 million global infections. Discrepancies in WB interpretations from institution to institution and country to country are just as dramatic today as they were ten or fifteen years ago. Unfortunately, until such time that we have an international standard for scoring WB results, any comparison of data from study to study, country to country, or year to year, will remain compromised. However, it cannot be overemphasized that even if the global research community were to eventually agree on a common set of rules for scoring WB, that still doesn't mean the results can be used to diagnose infection with HIV. According to the manufacturer quoted above, the best we can do with a positive WB declaration is to *presume* it is positive for antibodies, which *may* indicate infection with HIV.
Some experts will argue that their declarations of infection are valid because the majority of individuals who have been told that they are infected also test positive on Viral Load (VL) tests; which detect fragments of RNA or DNA supposedly unique to the virus. However, according to the manufacturer of the only FDA approved PCR test on the market, their test, "is not intended to be used...as a diagnostic test to confirm the presence of HIV infection." (9) Other experts have warned, "the trend toward earlier and more aggressive treatment of HIV infection has lead to the inappropriate use of these [VL] assays," and that, "viral load tests for HIV-1 were neither developed nor evaluated for the diagnosis of HIV infection." (10) According to others, this is because, "there is no 'gold-standard' laboratory test that defines the true infection status, and a true positive PCR test cannot be distinguished from a false positive." (11)
Unfortunately, there is a systemic illusion in the research community that the magnificent Sensitivities and Specificities reported in the contemporary literature (for various HIV test kits) pertain to the tests ability to diagnose the presence or absence of HIV in a sample. In fact, these reported accuracies represent nothing more than measures of concordance between various antibody test kits; none of which have been validated or approved for diagnosing infection with HIV. Since all of these tests are based on the same molecular principle of antibodies in a particular sample binding to prepared antigens in a test kit (be they on plastic plates, beads, microspheres, or nitrocellulose strips), it is not surprising that concordance between various test kits is quite high. However, even a 100% concordance between two different tests does not justify the use of either for purposes other than what they have been validated and approved for.
In summary, there simply is no laboratory test that has ever been approved for medical use by the FDA that claims to be able to diagnose the presence or absence of HIV in any sample, with any degree of accuracy. Until we have such a laboratory test, debates over issues such as whether or not HIV is sexually transmitted are likely to go unresolved. A validated and approved test for diagnosing infection with HIV would undoubtedly serve as an invaluable contribution to our understanding of AIDS, and to our ability to effectively manage the millions who suffer its effects.
References:
1. Licensed / Approved HIV, HTLV and Hepatitis Tests. http://www.fda.gov/cber/products/testkits.htm
2. CDC. MMWR 1987; 36:509-15.
3. UNAIDS/WHO. AIDS epidemic update December 2001; UNAIDS/01.74E - WHO/CDS/CSR/NCS/2001.2 (www.unaids.org).
4. Suzan Cruzan. FDA News Release April 30, 1987; P87-11.
5. Abbott Laboratories, Abbott Park Il. Package Insert for Human Immunodeficiency Virus Type 1 [Abbott] HIVAB[TM] HIV-1 EIA. US License No. 43, January, 1997.
6. Genetic Systems Corp., Redmond WA. Package Insert for Genetic Systems HIV-1/HIV-2 Peptide EIA. US License No. 978, Revised February 2000.
7. Cambridge Biotech Coirp., Rockville MD. Package Insert for HIV-1 Western Blot. US License No. 1063. June 2, 1998.
8. Epitope, Inc., Beaverton, OR. Package Insert for OraSure[R] HIV-1 Western Blot Kit. US License No. 1133, January 10, 1996
9. Roche Diagnostic Systems, Inc., Branchburg, NJ. Package Insert for Amplicor[R] HIV-1 Monitor[TM] Test. US License No. 83088, 1996.
10. Rich JD, et al. Ann Intern Med 1999, 130:37-9.
11. Sheppard, HW, et al. JAIDS 1991; 4:819-23.
Rodney Richards
Competing interests: None declared

AIDS. South African Government Now Treating Rather Than Debating the Deadly Disease. 4 March 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia
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Re: AIDS. South African Government Now Treating Rather Than Debating the Deadly Disease.

Dr Manto Tshabalala-Msimang, , South Africa's Minister of Health recently stated:

"I have made it clear that our priorities this year include the expansion of the prevention of mother-to-child-transmission of HIV programme and increased funding for post-exposure prophylaxis for survivors of sexual assault."
Few have summed up this (alleged) debate as well as Peter Flegg has in his response:

"What is taking place on this forum is a farce, not a debate. A debate consists of two parties discussing evidence for and against a contentious position, with the aim of reaching some definitive conclusion or consensus. Dissidents like to refer to these interchanges as "scientific debate" since this lends veracity to their contention that there is uncertainty about HIV"
Great to see that the South African Government is now getting on with saving lives and allocating less time to farcical 'debates.'

***
Competing interests: None declared

Diagnostic philosophy and a response to Richards 5 March 2003

Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital, UK, FY3 8NR
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Re: Diagnostic philosophy and a response to Richards

I am grateful that Rodney Richards has pursued the topic of HIV diagnosis, since it affords me the opportunity to put the concept of �diagnosis� into clinical perspective.
The diagnosis of a medical condition is the direct responsibility and prerogative of the clinician concerned. He/she should use all available information such as history of the illness, examination findings and results of laboratory tests in order to reach a diagnosis. There is a fundamental difference in the way in which clinicians and non-clinicians regard tests for the diagnosis of disease, and this is revealed in much of the above debate on HIV testing. With some diseases, tests are so definitive that they can establish a diagnosis on their own merit (e.g. a biopsy showing malignancy). For other conditions, tests are insufficiently robust and additional clinical information is required to reach a probable diagnosis (e.g. acute coronary syndromes). So where do we stand with HIV?
In usual practice, HIV tests are employed in both a parallel and serial fashion. When interpreting the result of a test, it is not merely a question of the sensitivities and specificities, but of probabilities and odds. Likelihood ratios reflecting these odds are perhaps the best way to evaluate the relevance of results. They provide useful information, particularly when tests are used in series, as is often the case in HIV infection. The post-test odds of the first test become the pre-test odds for the second test, and so on, arriving at a final post-test probability that enables a diagnosis to be reached with a high degree of precision.
The initial battery of tests for suspected HIV infection will include an ELISA, usually followed by a further ELISA and then confirmatory Western Blot (or in England an additional ELISA). A second sample of blood from the patient is retested (to confirm it is the right patient's blood). Those who are HIV positive will have subsequent tests which are incorporated into the diagnostic algorithm, at each stage increasing the post-test probabilities of a positive diagnosis (viral load assays, HIV sequencing to determine subtype and resistance mutations, immunological profiling etc.). It is the clinician that ultimately decides on the significance of all these test results, and not the kit manufacturers. When one is faced with the clinical scenario of a patient with repeated positive HIV antibody assays, positive confirmatory Western Blot, HIV viral load of 58000 copies/ml, Subtype B infection, no resistance mutations, CD4 lymphocyte count of 26/ml, it hardly requires the inputting of clinical information that he has thrush and Pneumocystis jiroveci pneumonia to reach a diagnosis of HIV.
All that HIV antibody tests can do is test for the presence of antibody to HIV, and nothing more. Since there is always a tiny chance of false positivity occurring, no antibody test kit manufacturer (for any test anywhere) is going to claim that a positive test confirms infection, and the numerous quotes from test kit inserts that Richards quotes merely confirm this fact. I can see nothing wrong with them claiming that positive tests are "presumed" to demonstrate HIV antibodies, since that is the presumption of the test.
Richards claims that the kit manufacturers and FDA "explicitly warn against the use of these tests for diagnosing infection". If there is a reference to this explicit warning, I would like to see it, rather than quotations that the longer term risks of developing AIDS are unknown.
Richards is also incorrect concerning the use of antibody tests in diagnosis. He states some countries use a "single ELISA" to make a diagnosis. A single ELISA may be employed for screening or epidemiological reasons, but is insufficient to make a diagnosis. In some resource-poor countries with a high prevalence of HIV, this might be used for logistical reasons when doctors are faced with a patient who has a suspected AIDS- defining illness, but in these situations even a single ELISA is a relative luxury and would better be kept for antenatal or blood donor screening.
As regards Western Blots, Richards refers to differing interpretation of band patterns between certain countries, whilst acknowledging that the interpretive criteria are still evolving. He is wrong to state that someone in Australia, France or the UK showing bands to p24 and gp160 would be told they are not infected. A negative Western Blot requires the total absence of any bands whatsoever. Anyone who has a band pattern that is not indicative of HIV infection will be told that the result is "indeterminate", not told they are HIV negative. An indeterminate result may represent several things, including cross-reacting antibodies (often to p24 antigen), early infection, or advanced HIV/AIDS. Indeterminate results should be rechecked at 6 weeks and 3 months to pick up those who are seroconverting. The interpretation of results in those who are HIV ELISA positive but persistently WB indeterminate (an unusual scenario in clinical practice) will be up to the clinician concerned, and if he chooses to use additional tests such as viral load to improve his post- test probability then I say well done for carrying out an appropriate clinical decision analysis of the situation.
Richards concludes: "there simply is no laboratory test that has ever been approved for medical use by the FDA that claims to be able to diagnose the presence or absence of HIV in any sample with any accuracy". Firstly, the tests in question do not look for HIV, but HIV antibodies. Secondly, they do this with considerable accuracy.
Richards quotes Thomas Kuhn (The Structure of Scientific Revolutions, 1962). Yes, each group will use its own paradigm to argue in that paradigm�s defence. Kuhn describes these paradigms as the basic gestalt within which science interprets the evidence it has available. But he claims there are no independent data by which to decide between competing paradigms. This implies that all theories or paradigms have equal scientific merit, a concept that rings false in my ears. My own view is more aligned to that of William of Occam (he of Occam�s razor) and to that of Karl Popper (The Logic of Scientific Discovery, 1934), who stated that when you have a choice of theories, you should accept the one that is better corroborated than the others. Ask any practicing clinician which philosophy he prefers. I certainly hope that when I am lying in a cardiac unit with chest pain that my physician agrees with Popper and not Kuhn!
This does not presuppose that I have a disinclination for alternative interpretations of the HIV construct. I merely wish that competing/alternative explanations should be able to provide sufficient evidence for their hypotheses and to be able to stand up to rigorous scientific scrutiny. The dissidents� theories concerning HIV/AIDS do neither. They have no credible alternative theories to HIV, but confine themselves to trying to nibble at areas of mainstream scientific uncertainty, hoping that by pointing out tiny inconsistencies they can persuade themselves and others that the whole concept is inconsistent and therefore mistaken.
Competing interests: None declared

Rakai Project Showed Link Between Viral Load and Heterosexual Transmission 5 March 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Rakai Project Showed Link Between Viral Load and Heterosexual Transmission

In a response entitled 'Heterosexual transmission and credibility' the Rakai Project Study Group(1) was cited.
Further reading reveals that:

"The viral load is the chief predictor of the risk of heterosexual transmission of HIV-1, and transmission is rare among persons with levels of less than 1500 copies of HIV-1 RNA per milliliter. "
So the more virus, the more chance that it can be transmitted heterosexuality. Continuing to insist that heterosexual transmission of HIV is not possible is a bit like arguing that all sheep are white - you only have to find one black sheep to end the discussion.

References:
(1) Quinn TC, Wawer MJ, Sewankambo N, Serwadda D, Li C, Wabwire-Mangen F, Meehan MO, Lutalo T, Gray RH. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med 2000 Mar 30;342(13):921-9

Competing interests: None declared

Re: HIV/AIDS - there is no "debate" 5 March 2003

Todd Miller,
researcher
Miami 33136
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Re: Re: HIV/AIDS - there is no "debate"

Peter J. Flegg wrote, "...5000 scientists at the Durban International AIDS conference signed up to a "Durban Declaration" to this effect and to refute the disidents' claims."
I don't think this is a proper document to reference in support of the HIV theory of AIDS. The motivation for writing it was because the establishment felt threatened, nothing more. In that sense, it was a small victory for those questioning the theory, since the declaration acknowledged the threat. It is basically non-scientific propaganda written to appear as an authoritative document intended to stifle debate, a thoroughly anti-scientific endeavor.
One could easily imagine a situation 20 years ago, when the cause of ulcers was thought to be excess stomach acid or any of several other non- specific causes. If there was a perceived threat to this notion, doctors would have readily signed any document "declaring" the cause of ulcers. How would they feel when Dr. Marshall made his discovery? Would they suddenly remember their scientific training, assuming they learned it at all?
The history of medicine and science if full of such examples. They are often caused by deviations from the scientific method (I would consider the Durban Declaration and any reference to it as that), and we ignore them at our peril.
Also, to those who would try to stifle this debate by arguing that to even discuss it is "dangerous", I would remind you that this debate has been going on for nearly 15 years, and during that time I've found that the it is not easy to find anyone who has heard of Peter Duesberg or these ideas. During the same time new cases have declined. Dr. Padian's transmission frequencies are still a secret to the public, as is this debate. Let's stick to the science and leave moral admonitions out.
Competing interests: None declared

The Padian Paper Does NOT Support Alternative AIDS Theories 6 March 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia
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Re: The Padian Paper Does NOT Support Alternative AIDS Theories

A response above has claimed that:

"Dr. Padian's transmission frequencies are still a secret to the public"
NO, they are not a secret to the public, they are available online(1)
Padian's paper does not prove that HIV can't be transmitted sexually because:
Although there were no NEW transmissions during the study period:
1. All participants were aware that they were with a HIV-positive partner.
2. They all new that they were part of a study examining transmission.
3. Condom use increased substantially during the study period.
4. Anal sex decreased substantially during the study period.
5. The whole world does not live in North Carolina.

References:
(1) Padian NS. Shiboski SC. Glass SO. Vittinghoff E. Heterosexual transmission of human immunodeficiency virus (HIV) in northern California: results from a ten-year study. American Journal of Epidemiology. 146(4):350-7, 1997 Aug 15. [Abstract]

Competing interests: None declared

Antiretorvirals and risk of foetal brain injury 6 March 2003

Richard G Fiddian-Green,
None
None
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Re: Antiretorvirals and risk of foetal brain injury

I have repeatedly drawn attention to the relevance of the adequacy of mitochondrial oxidative phosphorylation to health including that of the foetus and infant in these rapid responses. Some three years ago I also drew the attention of the WHO representive in Cape Town (Professor Folb)and a minister, who is a doctor in President Mbeki's government offices in Cape Town (Asmal), to the potential risks of causing brain injury in the foetus by treating pregnant women with anti-retrovirals (1,2). To my astonishment limited use for pregnant women was approved soon after. An astonishing decision especially as the drugs might compound the effects of other mitochondrial poisons to which pregnant mothers are almost certainly exposed in South Africa.
1. McComsey G. Update on mitochondrial toxicity of antiretrovirals and its link to lipodystrophy. AIDS Rev. 2002 Jul-Sep;4(3):140-7. Review.
2. Tan S, Zhou F, Nielsen VG, Wang Z, Gladson CL, Parks DA. Increased injury following intermittent fetal hypoxia-reoxygenation is associated with increased free radical production in fetal rabbit brain. J Neuropathol Exp Neurol. 1999 Sep;58(9):972-81.
Competing interests: � None declared

Survival in HIV-infected children has greatly improved with antiretroviral therapy. 7 March 2003

Tony Floyd,
Medical Student
Newcastle University, Australia 2308
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Re: Survival in HIV-infected children has greatly improved with antiretroviral therapy.

The McComsey paper referred to above is also available online(1).
As you can read for youself, it does review the clinical consequences of the toxicities of antiretroviral drugs.
Does Grace McComsey recommend against the use of such drugs? One might be tempted to look at her other papers to see if, at long last, a prominent researcher is against antiretroviral drugs.
For example, her January 2003 paper(2) states that:

"Survival in HIV-infected children has greatly improved with the introduction of highly active antiretroviral therapy."
This and other papers by McComsey prove that she, like thousands of others, are getting on with the job of improving existing therapies for what is a real and tragic illness. Citing her work in an attempt to support alternative viewpoints may only convince people who either aren't sceptical of extraordinary claims, or don't wish to check the facts.
References:
(1) McComsey G. Update on mitochondrial toxicity of antiretrovirals and its link to lipodystrophy. AIDS Rev 2002 Jul-Sep;4(3):140-7 [Abstract]
(2) Leonard EG, McComsey GA.Metabolic complications of antiretroviral therapy in children. Pediatr Infect Dis J 2003 Jan;22(1):77-84 [Abstract]
Competing interests: None declared

An abuse of surrogate markers for AIDS 10 March 2003

David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583
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Re: An abuse of surrogate markers for AIDS

It should come as a shock, no doubt, to learn that if three laboratory tests somehow disappeared or were outlawed (HIV antibody test, CD4 cell count, PCR viral load test), then AIDS, as commonly understood, would formally vanish from the USA and Europe. The three laboratory tests in question are called surrogate markers because they stand in for either AIDS itself or for its supposed cause, HIV. According to the current definition of AIDS, no matter how sick an American or European is with AIDS-defining diseases, he or she cannot be classified as an AIDS case if antibodies to HIV are not present. In other words, for an American or European doctor to diagnose pneumonia, TB, dementia, cervical cancer, etc. as AIDS it is necessary to obtain laboratory test results that satisfy the definition of AIDS. Since the HIV- antibody test has been discussed in depth already, I will limit my remarks to CD4 cell counts and viral load.
At the beginning of the AIDS epidemic, it was already recognized as probably a mistake to use CD4 as a marker of AIDS or even a measure of therapeutic effectiveness. In 1981, James Goodwin, MD, wrote what he called "a diatribe against the measurement of T-cell subsets in human diseases" [1]. His "diatribe" began: "It's starting again. ...The T- and B-cell measures--having run through the sick, the elderly, the young, the pregnant, the bereaved--had finally run out of diseases. Each condition was the subject of many reports; so that now, to give but one example, we can conclude with some assurance that T-cell numbers are up, down, or unchanged in old folks. And it's starting all over again, this time with T-cell subsets."
"What will they find?" he asked. "Sometimes the suppressor cell markers will be up and helper cells down; sometimes the suppressor cells will be down and the helper cells up; sometimes they'll be unchanged--and various combinations of the aforementioned. ...My strongest argument is this: Measurement of T and B cells and their subsets in diseases has no clinical meaning."
"Nonimmunologists have naturally assumed that any subject occupying so much journal space must be relevant in some way--a logical but incorrect assumption. ...And while the identification of T- cell subsets in mouse and man represents a major breakthrough in the understanding of immunoregulation, the enumeration of these subsets in myriad diseases largely represents a waste of time".
As recently as 1998, Mario Roederer of Stanford University confirmed Goodwin's assessment that an obsession with T-cell subsets in AIDS patients has been a mistake: "[T]he facts (1) that HIV uses CD4 as its primary receptor, and (2) that CD4+ T cell numbers decline during AIDS, are an unfortunate coincidence that have led us astray from understanding the immunopathogenesis of this disease" [2].
Prior to Roederer's remarks, the use of the CD4 (T-cell counts) as a surrogate marker of disease progression was also criticized by the authors of the Concorde Study, the largest clinical trial evaluating the use of AZT: The authors concluded that:
"The small but highly significant and persistent difference in CD4 count between the groups was not translated into a significant clinical benefit. Thus, analyses of the time until certain concentrations of CD4 were reached (eg, 200/_L, 350/_L, or 50% of baseline) revealed significantly shorter times in the Def[erred] group. Had such analyses been regarded as fundamental, the trial might have been stopped early with a false-positive result. This discrepancy in the differences between Imm[ediate] and Def groups in terms of changes of CD4 count and of long-term clinical response casts doubt on the uncritical use of CD4 counts as 'surrogate endpoints' in trials..." [3].
Thomas Fleming and David DeMets have stated that, "The use of surrogate end points has probably been more intensely discussed in the design and analysis of clinical trials of HIV infection and AIDS than in any other area" [4]. However, "Predictions having an accuracy of approximately 50%, such as the accuracy seen with the CD4 count in the HIV setting, are as uninformative as a toss of a coin." With regards to clinical trials and FDA approval of anti-HIV drugs, Fleming and DeMets have warned that, "Surrogate end points are rarely, if ever, adequate substitutes for the definitive clinical outcome in phase 3 trials" [4].
Indeed, a summary result from a 1993 state-of-the-art conference had previously concluded that the effect of treatment on the most popular surrogate, CD4 cell count, did not accurately predict the effect of treatment on the clinical outcomes, that is, progression to AIDS or time to death [5]. Nevertheless, with the exception of the early AZT clinical trials, all subsequent anti-HIV drug trials and FDA approvals have relied exclusively on the measurements of these surrogate markers and not on the real clinical outcomes, such as morbidity and mortality, that matter to most people.
A year later, Fleming stated that, "It is very apparent one cannot simply consider establishment of statistically significant treatment effects on CD4 cell counts to be a valid surrogate for either of the two clinical endpoints. When the progression to AIDS/death endpoint was positive, the CD4 endpoint appropriately was significantly positive in 7 of 8 trials; unfortunately however, the CD4 endpoint was significantly positive in 6 of 8 trials in which the progression to AIDS/death endpoint was negative. The relationship of CD4 effects and survival is even more unsatisfactory. The CD4 endpoint was significantly positive in only 2 of 4 trials in which the survival endpoint was positive; yet it was significantly positive in 6 of 7 trials in which the survival endpoint was negative. In three other trials, survival trends were observed which were in the opposite direction of significant treatment effects on CD4" [6].
The well-recognized problems with CD4 counts eventually led to its being replaced by the PCR viral-load test as the primary surrogate marker to be used in anti-HIV drug clinical trials. But, the "viral load" test has its share of problems. To start with, Roche's "AMPLICOR HIV-1 MONITOR Test is not intended to be used as a screening test for HIV or as a diagnostic test to confirm the presence of HIV infection" (Roche Diagnostic Systems AMPLICOR HIV-1 MONITOR Test package insert, PMA No. BP950005/4).
To save space, below is a list of some of the problems with the viral load test that were published in the scientific, medical literature:
False positive or false negative? It depends on the answer you want. Apparently, absence of antibodies to HIV trumps a high viral load result.
Schwartz D. H. et al., "Extensive evaluation of a seronegative participant in an HIV-1 vaccine trial as a result of false-positive PCR" (1997) The Lancet 350: 256-259.
An individual tested positive by PCR, but was antibody negative. Therefore, the patient's viral load of 100,000 copies of RNA per ml was called false-positive. It took $5000 worth of PCR testing in several labs to get the "right" answer: negative.
----------------------
Christine Defer et al., "Multicentre quality control of polymerase chain reaction [viral load] for detection of HIV DNA" (1992) AIDS 6: 659-663
"False-positive and false-negative results were observed in all laboratories (concordance with serology ranged from 40 to 100%)."
---------------------
Michael P. Busch et al., "Poor sensitivity, specificity, and reproducibility of detection of HIV-1 DNA in serum by polymerase chain reaction" (1992) Journal of Acquired Immune Deficiency 5: 872-877.
"The results indicate that current techniques for detecting cell-free HIV-1 DNA in serum lack adequate sensitivity, specificity, and reproducibility for widespread clinical applications."
"In any event, the levels of viral (and cellular) DNA in serum appear to be so low that reproducible detection, even with use of PCR, is not currently possible."
---------------------
Josiah D. Rich et al., "Misdiagnosis of HIV infection by HIV-1 plasma viral load testing: a case series" (1999) Annals of Internal Medicine 130: 37-39.
"The availability of sensitive assays for plasma HIV viral load and the trend toward earlier and more aggressive treatment of HIV infection has led to the inappropriate use of these assays as primary tools for the diagnosis of acute HIV infection."
"Physicians should exercise caution when using the plasma viral load assays to detect primary HIV infection..."
"Plasma viral load tests for HIV-1 were neither developed nor evaluated for the diagnosis of HIV infection..."
------------------------
M. Piatak et al., "High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR" (1993) Science 259: 1749-1754.
"Plasma virus levels determined by QC-PCR correlated with, but exceeded by an average of 60,000-fold, virus titers measured by endpoint dilution culture."
In fact, 53% of the viral load positive patients had no culturable HIV.
"For HIV-1 propagated in vitro, total virions have been reported to exceed culturable infectious units by factors of 10,000 to 10,000,000, ratios similar to those we observed in plasma."
----------------------
Haynes W. Sheppard et al., "Viral burden and HIV disease" (1993) Nature 364: 291.
"...the high level of plasma virus observed by Piatak et al. [reference above] was about 99.9 per cent non-culturable, suggesting that it was either neutralized or defective. Therefore, rather than supporting a cytopathic model, this observation actually may help explain the relatively slow dissemination of the infected cell burden and thus the relative ineffectiveness of therapy with nucleoside analogues which target this process.
"...we question the longitudinal conclusions some of these investigators have drawn from cross-sectional data. The results presented are equally consistent with the conclusion that higher viraemia is a consequence of, rather than the proximate cause of, defective immune responses."
----------------------
Simply put: the AIDS surrogate markers are being abused. These surrogate markers are causing a great deal of harm by labeling people with myriad diseases and conditions--even healthy people who only have antibodies to HIV--as having incurable AIDS, which is said to be invariably fatal. The surrogate markers are also being used to obtain FDA approval of clinically ineffective AIDS chemotherapies that are highly toxic and even lethal if taken long enough.
David Rasnick
References
1. Goodwin, J. S. (1981) OKT3, OKT4, and all that, Journal of the American Medical Association 246, 947-948
2. Roederer, M. (1998) Getting to the HAART of T cell dynamics, Nature Medicine 4, 145-146
3. Seligmann, M., et al. (1994) Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection, Lancet 343, 871-881
4. Fleming, T. R., et al. (1996) Surrogate end points in clinical trials: are we being misled?, Annals of Internal Medicine 125, 605- 613
5. Sande, M. A., et al. (1993) National Institute of Allergy and Infectious Diseases state-of-the-art Panel on Anti-retroviral therapy for adult HIV-infected patients, Journal of the American Medical Association 270, 2583-2589
6. Fleming, T. R. (1994) Surrogate markers in AIDS and cancer trials, Statistics in Medicine 13, 1423-1435
Competing interests: None declared

Re: HIV drugs fail children 11 March 2003

Peter J Flegg,
Consultanat Physician
Blackpool Victoria Hospital, UK FY3 8NR
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Re: Re: HIV drugs fail children

http://bmj.com/cgi/eletters/326/7381/126/e#29986
David Rasnick claims he has "scoured the literature" for evidence of the benefits of HIV therapy in children. I suggest he has not tried nearly hard enough. Instead he has come up with several references showing that HIV drugs have side effects in children (but no evidence that they have no benefits). I am willing to accept that the drugs have side effects. I know that every paper can reveal different things to its readers, myself included. But let us be clear. Here we are asked to consider evidence that the drugs "do not prolong lives or improve quality of lives", and therefore we must scrutinise carefully each reference Rasnick cites and see if it meets his criteria. In fact none of the studies quoted are suitable for verifying his claims. What actually becomes clear from Rasnick�s citations is that he is unable to comprehend what amounts to appropriate evidence and he displays a total lack of understanding about clinical trial methodology.
Several of the trials he quotes are phase I/II studies. For Rasnick�s enlightenment, I should point out that a Phase I trial is used to determine the maximum tolerated dose and to define the toxicities of the treatment. Phase II studies will help determine whether the drug has the desired effect. It is inevitable that some patients will experience adverse effects. Using these trials (which are specifically designed to determine safety and tolerability of a drug), to make specious claims about clinical efficacy and other properties which are outside the remit of the trial methodology is poor science. He also seems to be confused as to when trials should have control groups, being critical (unless it suits his purpose) of trials which quite appropriately are uncontrolled.
Additionally, in a clinical trial, any clinical event is categorised as an adverse event, irrespective of its likely cause. For Rasnick to assume that all events are related to drug toxicity is misleading. An example of this can be found in the claim that in a trial of stavudine "Thirty-five of 37 subjects experienced serious clinical adverse events", with Rasnick�s implication being that stavudine is to blame (1). Actually the authors concluded: "One subject with baseline neurologic abnormalities experienced a transient episode of apparent pain or discomfort in her fingers, possibly related to stavudine. All other adverse events were attributed to underlying disease". Why doesn�t Rasnick report this fact, unless his intention is to mislead readers?
Another Phase I/II trial of zidovudine seems to concern Rasnick because of anaemia and neutropenia in trial subjects (2). Yes, these can be serious events, but this was a dose-ranging study, so toxicity at higher doses was not unexpected, and helped define the safety margins of zidovudine doses in the management of encephalopathy. Rasnick neglects to mention the study�s findings that "all children with encephalopathy improved with zidovudine treatment."
Yet another early Phase II trial from 1991 designed to study safety and tolerance of zidovudine seems to upset Rasnick (3). He claims the study, which had no control group by design, "acknowledges the shortcomings of not using controls". And all because the study stated: "although no control group was available for direct comparison, the improvement in the children in this study closely paralleled the observations in controlled studies of adults receiving zidovudine". My interpretation of this statement differs radically from that of Rasnick. I leave readers to make up their own minds what this sentence means.
Rasnick does raise the pertinent issue of zidovudine in prevention of mother to child transmission. There are already data from 5 randomised, zidovudine-placebo-controlled trials that show no difference in progression or mortality between HIV-infected infants exposed to placebo or zidovudine (4), but there are reports with the intriguing finding that HIV-infected infants may progress more rapidly if they received exposure to zidovudine compared to those who didn�t. This is likely to be related to the induction of zidovudine resistance in the affected infants, who respond less well when they progress to illness requiring therapy. There is no evidence for a similar effect in children who receive combination therapy in utero. Rasnick claims there is "clearly a dose response for the toxic effects of AZT treatment during pregnancy", but this is not clear to the authors of the paper he cites. They state that in utero transmission or transmission of zidovudine resistant virus is the most likely explanation.
Rasnick�s propensity to further misinterpret these results is demonstrated in his comments that "In short, if a mother takes AZT during pregnancy, her newborn is much more likely to get severely sick and die by age 3 than a newborn whose mother did not take AZT during pregnancy". This is incorrect, and takes no account of the fact that the use of zidovudine will greatly reduce the number of infected infants being born in the first place. What Rasnick should have said was "In short, if a mother takes AZT during pregnancy, her newborn, *IF HIV-INFECTED*, is much more likely to get severely sick and die by age 3 than an *HIV-INFECTED* newborn whose mother did not take AZT during pregnancy". I would also add the proviso that this has been shown only in cohort studies, but not shown to be the case in the other 5 randomised, controlled studies. In fact, in one of these, the progression rate for infected infants was nearly double for the infants who had received placebo (5). Rasnick says he wants controlled studies, but when they are available, he cites retrospective, uncontrolled studies instead. One can only wonder what his true intentions are.
Rasnick is probably an excellent chief scientist. However, I suggest he confines his future comments to his own field of laboratory methodology, and not to the clinical trials arena, which is difficult enough to understand without his unhelpful re-interpretation of published trials, which can only confuse the unwary.
(1) Kline MW, Dunkle LM, Church JA, Goldsmith JC, Harris AT, Federici ME, Schultze ME, Woods L, Loewen DF, Kaul S, et al. (1995): A phase I/II evaluation of stavudine (d4T) in children with human immunodeficiency virus infection. Pediatrics 96: 247-52.
(2) Pizzo PA, Eddy J, Falloon J, Balis FM, Murphy RF, Moss H, Wolters P, Brouwers P, Jarosinski P, Rubin M, et al. (1988): Effect of continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection. N Engl J Med 319: 889-96.
(3) McKinney RE, Jr., Maha MA, Connor EM, Feinberg J, Scott GB, Wulfsohn M, McIntosh K, Borkowsky W, Modlin JF, Weintrub P, et al. (1991): A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group. N Engl J Med 324: 1018-25.
(4) Mofeson LM, Munderi P. (2002): Safety of Antiretroviral Prophylaxis of Perinatal Transmission for HIV-Infected Pregnant Women and their Infants. JAIDS 30: 200-215.
(5) Connor EM et al. (1994). Reduction of maternal-infent transmission of human immunodeficiency virus type 1 with zidovudine treatment. N Eng J Med 331: 1173-1180.
Competing interests: Pharmaceutical-sponsored attendance at HIV conferences

Surrogate markers 11 March 2003

Peter J Flegg,
Consultant Physician
Blackpool Victoria Hospital, UK FY3 8NR
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Re: Surrogate markers

David rasnick States: "It should come as a shock, no doubt, to learn that if three laboratory tests somehow disappeared or were outlawed (HIV antibody test, CD4 cell count, PCR viral load test), then AIDS, as commonly understood, would formally vanish from the USA and Europe."
Would it come as a "shock" to be told that if blood glucose analysis was outlawed, then diabetes would disappear as a clinical entity? Very likely, because obviously it wouldn't.
I would remind Rasnick that clinical AIDS predated the HIV tests. Even if they somehow did not exist, the pandemic of immunodeficiency- induced illness that we have seen sweep the globe will not magically vanish.
Competing interests: None declared

Fleming and Seligmann do NOT support alternative AIDS theories... 11 March 2003

Tony Floyd,
Medical Student
Newcastle University, Newcastle Australia 2308
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Re: Fleming and Seligmann do NOT support alternative AIDS theories...

In a response entitled "An abuse of surrogate markers for AIDS" (10th March 2003), Professor Thomas Fleming from the University of Wisconsin Medical School has again been incorrectly cited as a supporter of alternative AIDS theories.
In his 1995 paper(1) he clearly states:

--- "The urgency of the Acquired immune deficiency syndrome (AIDS) epidemic has mandated that multiple therapeutic approaches be developed and that these approaches be evaluated through clinical trials." ---
The fact that he has also questioned various laboratory methods does not seem to have dented his belief in the need for therapies which save lives.
Maxime Seligmann has also, again, been misrepresented as supporting (alleged) theories that HIV drugs do no good. His 1999 Lancet article(2) states:

--- "Subcutaneous interleukin-2 is a convenient regimen that, as well as intravenous therapy, improves immunological function in HIV-1-infected patients receiving two nucleosides. Larger studies are needed to show whether immunological improvements translate into clinical benefit." ---
Seligmann hence studied whether or not interleukin-2 augments the treatment of patients receiving 2 anti-HIV drugs. Odd he would do such a thing if he thought the drugs were no good at all.
Apologies for re-posting the Seligmann material from a response on 01st March, but as long as the same false assumptions continue to be made about researchers I will have to keep pointing them out.
References:
(1) DeMets DL, Fleming TR, Whitley RJ, Childress JF, Ellenberg SS, Foulkes M, Mayer KH, O'Fallon J, Pollard RB, Rahal JJ, et al. The data and safety monitoring board and acquired immune deficiency syndrome (AIDS) clinical trials. Control Clin Trials 1995 Dec;16(6):408-21 [Abstract]
(2) Levy Y, Capitant C, Houhou S, Carriere I, Viard JP, Goujard C, Gastaut JA, Oksenhendler E, Boumsell L, Gomard E, Rabian C, Weiss L, Guillet JG, Delfraissy JF, Aboulker JP, Seligmann M. Comparison of subcutaneous and intravenous interleukin-2 in asymptomatic HIV-1 infection: a randomised controlled trial. ANRS 048 study group. Lancet 1999 Jun 5;353(9168):1923-9 [Abstract]

***
Competing interests: None declared

Re: Diagnostic philosophy and a response to Richards 12 March 2003

Rodney M Richards,
Independent AIDS Researcher
Louisville CO, 80027
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Re: Re: Diagnostic philosophy and a response to Richards

*The superior physician listens to the voice, the common physician observes the color, the inferior physician feels the pulse.* (T'ien-t'ai, Chinese scholar, 594 a.d.)
In response to my clarification that there currently exists no approved laboratory test for diagnosing infection with HIV, Peter J Flegg emphasizes: "[The clinician] should use all available information such as history of the illness, examination findings and results of laboratory tests in order to reach a diagnosis." In my opinion, this represents the spirit of the "superior physician" quoted above; and I have no issue with any physician who chooses to diagnose or treat any illness based on their clinical experience, with or without additional information from peripheral laboratory tests. I personally regard a physician's clinical experience to be far more valuable than any diagnostic test could ever hope to be.
However, Flegg goes on to suggest that when it comes to HIV, clinical information is not necessary to reach a diagnosis of infection: "When one is faced with the clinical scenario of a patient with repeated positive HIV antibody assays, positive confirmatory Western Blot, HIV viral load of 58000 copies/ml, Subtype B infection, no resistance mutations, CD4 lymphocyte count of 26/ml, it hardly requires the inputting of clinical information that he has thrush and Pneumocystis jiroveci pneumonia to reach a diagnosis of HIV."
The justification for his position on this issue is that: "The post- test odds of the first test become the pre-test odds for the second test, and so on, arriving at a final post-test probability that enables a diagnosis to be reached with a high degree of precision." While this is a true statement, it is important to note that none of the laboratory tests listed in the above scenario claim to be correlated with the presence or absence of HIV in a sample with any degree of probability whatsoever.
According to the manufactures of antibody tests, the best we can do with a sample that tests positive on ELISA and WB is to "presume" it is positive for antibodies to HIV. What precisely is the post-test probability that such a sample is infected with HIV? Is it 99.9%? Is it 5%? The answer is, we don't know because it has never been determined. It is unknown.
The manufacturers of FDA approved viral load (VL) and HIV resistance tests make no claim that their products can be used to predict the presence or absence of HIV in a sample with any degree of probability whatsoever; and the package inserts for both of these tests explicitly warn their products are "not intended to be used...to confirm the presence of HIV infection." (1) In other words, the post-test probability that a sample is infected with HIV cannot be determined using these tests. It is unknown.
The FDA has never even approved a sub-typing test for HIV, let alone one that claims to be correlated with infection. And finally, laboratory methods for determining CD4 counts are neither approved nor specific for diagnosing infection with HIV. As such, the post-test probability that a sample is infected with HIV cannot be determined using these tests. It is unknown.
Since the pre- and post-test probability that a sample is infected with HIV is unknown for every single test listed in the above clinical scenario, I assert that the combined probability is also necessarily unknown. Perhaps this is why the manufactures of these tests along with the FDA also claim the "significance of antibodies to HIV in an asymptomatic individual is not known."
Flegg asserts I am wrong in saying some countries use a single ELISA for the purpose of diagnosing infection with HIV. In fact, the use of a single ELISA for diagnosing infection in certain populations is a recommendation put forth by UNAIDS/WHO. According to their 1997 revisions, a single ELISA is sufficient "to confirm the clinical diagnosis of [HIV in] individuals meeting the WHO criteria of stage III or IV of HIV infection and when the HIV prevalence in the sample population (e.g., patients from a tuberculosis ward) is above 30%." (2) This report also recommends that in cases where two ELISA algorithms are used for diagnosing infection, persons with stage III or IV conditions should be considered infected even if they test negative on one of the two ELISAs.
In other words, a single positive ELISA is considered sufficient to tell persons in the less developed World that they are infected with HIV, provided they are experiencing conditions such as weight loss of more than 10%, chronic diarrhea, prolonged fever, oral candidiasis, oral hairy leukoplakia, pulmonary TB, or bacterial infections (Stage III conditions). (3)
Flegg goes on the assert I am, "wrong to state that someone in Australia, France or the UK showing bands to p24 and gp160 would be told they are not infected." Had I made such a statement I would be wrong. However, I actually said such a person would not be told that they "are" infected. Indeed they would be considered indeterminate and therefore receive the benefit of follow-up testing, which may well confirm them to be uninfected. In contrast, had such an individual lived elsewhere in the world, they would have been declared unequivocally infected and therefore understandably never subjected to retesting. Is this a likely scenario?
Flegg suggest the likely outcome of follow-up testing for individuals initially WB indeterminate is either an eventual positive result (representing early seroconversion), or an "unusual" persistently indeterminate result. This may well be in the case for individuals in risk groups living in industrialized nations, however, the situation is dramatically different in the developing world.
For example, of 63 pregnant women in the Congo who tested positive on ELISA and indeterminate on WB, and who were retested 3 months later, "[t]wenty-five (41%) of those retested became negative, and 36 (59%) remained indeterminate." (4) Only two women (3.2%) in this study developed positive Western blot patterns. According to the authors of a more recent study using blood collected from Ethiopians in various community cohort studies: "Of 31 WB assays initially indeterminate...and with follow-up samples, 29 (93.5%) became negative when retested subsequently while 2 (6.5%) remained indeterminate for more than a year and were thus considered negative." (5) In other words, 100% of individuals with WB indeterminate results in this study were found to be uninfected on follow-up. According to data in this study, had these uninfected individuals lived in the USA where the CDC criteria is used, 19.4% of them would have been declared infected. This being the case, none of these individuals would have ever come to find out that they are currently negative for all bands on WB.
These examples vividly illustrate how discrepancies between institutional criteria for scoring WB results can have a profound effect on whether or not someone is told they are infected or retested. Since various ELISA testing algorithms are selected and tuned to concord with these various institutional criteria for scoring WB, they are likewise predisposed to this same phenomenon.
Flegg contends that dissidents hope "by pointing out tiny inconsistencies they can persuade themselves and others that the whole concept [of HIV/AIDS] is inconsistent and therefore mistaken."
According to UNAIDS and the WHO, 25 million humans on this planet have died from infection with a deadly virus, and another 40 million are estimated to be currently infected. Yet, after 20 years of research supported by $100 billion in public funds, we still don't have a have single diagnostic test approved by any government in the developed world that claims to be able to determine whether or not any given individual is infected with this deadly virus. This is not a "tiny inconsistency." It is time for the mainstream research community to stop ignoring this serious deficiency in AIDS research; and to redirect funds as well as research efforts to the goal of developing a reliable laboratory test intended for use in diagnosing infection with this virus. The citizens of this planet, especially those suffering the devastating consequences of AIDS, deserve such a test.
References:
1. TRUGENE [TM] HIV-1 Genotyping Kit. Visible Genetics Inc., Toronto, Ontario.
2. WHO. Wkly Epidemiol Rec 1997; 72:81-88.
3. WHO. Wkly Epidemiol Rec 1990; 65:221-8.
4. Lallemant M, et al. JAIDS 1992; 5:279-85.
5. Meles H, et al. Clin Diagn Lab Immunol 2002; 9:160-3.
Rodney Richards
Competing interests: None declared

Reply to Flegg 13 March 2003

David Rasnick,
Chief Science Officer, Boveran, Inc.
San Ramon, CA 94583
Send response to journal:
Re: Reply to Flegg

Peter Flegg said that, "AIDS predated the HIV tests". That is so true. That was back in the days before HIV-dogma had taken over- -in the days when questions were allowed and debate possible in the USA. However, after three major definition changes as to what constitutes AIDS in the USA, antibodies to HIV is now forced by definition to determine a diagnosis of AIDS. Conversely, a person suffering from the exact same AIDS-defining diseases but who is confirmed to test negative for those antibodies is precluded, by definition, from being diagnosed with AIDS. The CDC now calls such HIV-free AIDS cases by the highly memorable name of Idiopathic CD4 Lymphocytopenia (ICL) [1]. So, the AIDS-defining diseases don't change--they remain the same as always--it's only their names that change. That's why outlawing the HIV antibody and viral load tests would eliminate diagnosing new cases of what is commonly understand as AIDS because there would be no way of knowing if someone had antibodies to HIV or not--whether someone had AIDS or ICL. If it's AIDS, you get AZT and other DNA chain-terminators. If ICL, you're treated for good old-fashion pneumonia, TB, c