Canadian aboriginals in Vancouver face AIDS epidemicBMJ 2003; 326 doi: https://doi.org/10.1136/bmj.326.7381.126/e (Published 18 January 2003) Cite this as: BMJ 2003;326:126
All rapid responses
The AIDS denialists should look into a few multi-billion dollar sources of funding:
1) The clotting factor industry has paid out hundreds of millions of dollars to HIV-infected hemophiliacs. They could have saved a lot of coin if the denialists were able to cast coubt on HIV as the cause of AIDS.
2) The porn film industry seems to be convinced that HIV can be sexually transmitted, and it is costing them several million dollars this spring alone.
If the AIDS denialists really had any significant information on this topic, they could easily make millions of dollars selling that information.
Competing interests: No competing interests
Perhaps I can comment on what David Rasnick views as a lack of
supporting evidence for a beneficial effect of anti-HIV therapy in
children. In one sense he has a point, because there are fewer studies
reported in children than adults. For a number of reasons
(medicolegal/ethical, practical and logistical), drug trials in children
will always be less satisfactory than in adults. New drugs are initially
studied in adults, and even when shown to be effective, there can be
problems repeating satisfactory similar studies in children. No one wants
to reinvent the wheel and deny children treatment that has been shown to
be effective in adults, and often studies are less robust and fail to meet
level I requirements for evidence. This is true for almost all paediatric
therapies, not just HIV. However most paediatric studies of HIV drugs
reach level IIa or IIb requirements, and are deemed sufficient for drug
In the case of children with HIV, the natural development of drug
trials was firstly monotherapy with AZT (level IIb, uncontrolled), then
progressing to dual versus monotherapy (level IIa, controlled [PACTG 152,
PACTG 300, PENTA 3 and Penta4]) and then triple combination therapy (level
IIa, such as PENTA5), and some four drug combinations (level IIa).
Unfortunately Rasnick seems to want what is accepted as current standard
of care (triple therapy) to be tested in a phase III, randomised, placebo-
controlled trial. This will never take place and would be totally
unethical, given the weight of evidence for benefit. New drugs or
combinations of drugs must be tested against the most effective existing
therapy, and not against placebo. How would Rasnick feel if his child had
leukaemia, andwas asked to participate in the trial of a new drug
combination, but those conducting the trial insisted his child take part
in a randomised, double blind trial of the drug matched against a
placebo?. Contrary to what Rasnick asserts, there are many phase III
studies in children as pointed out above, but these have compared drugs to
drugs, and not to placebos.
I am entirely comfortable with the evidence that the drugs benefit
adults (indeed there are several meta-analyses to demonstrate this even to
level Ia evidence) (see refs 1,2,3). If one drug is better than none, and
two better than one, and three better than two, I am quite willing to
arrive at the logical conclusion the three are better than none. I am also
happy that there is more than enough corroborative evidence that the drugs
also work in children. There are also the results from longitudinal cohort
studies, like the the PACTG 219 study, and the Italian Register referred
to earlier. I am sorry that the significance of this type of study escapes
Rasnick – instead of accepting its conclusions, he tries to say "Oh, it's
only a cohort study" and tries to trivialise its methodology and
reinterpret its results. Rasnick states the Register "compared the
outcomes of three arbitrary groupings of patients from different periods
of the epidemic. This approach is highly deceptive and is at best bad
science". The grouping was not "arbitrary" – it was determined by calendar
year of availability of new HIV therapy strategies. Would Rasnick call
grouping in a study on the morbidity of diabetes "arbitrary" because it
looked at outcome pre- and post-insulin? This may not be perfect science,
but by no means is it "bad science".
There are still significant causes for concerns about therapy in
children , particularly long term toxicity and sustainability.
Nevertheless, there is clear evidence for benefit when treatment is
started at an appropriate stage of infection. I refer Rasnick to an
excellent source of information on paediatric HIV which contains many of
the relevant references
Finally, Rasnick asks why I brought up the McSherry analysis of PACT
076. I did this to point out that in this (randomised, placebo-controlled)
study, as with others, there was no deleterious effect noted in the
children with HIV who had received zidovudine perinatally. Rasnick states:
...."here's how McSherry et al. summed up their results that Flegg says
support his contention. "In this limited study, zidovudine therapy during
pregnancy and labor and in the neonatal period for 6 weeks failed to have
a major effect on rapid progression of disease, timing of transmission,
and viral replication in HIV-infected infants." Given that conclusion, I
say that the results of the McSherry et al. better study support my
contention than his".
I would like to remind Rasnick that it was his contention that
perinatal zidovudine actually caused HIV infected children to progress
more rapidly than those who received none. McSherry's conclusions that
Zidovudine failed to have any effect on progression (either advantageous
or deleterious) therefore support my contention, and not his. I would also
point out (again) that Rasnick's claims for his contention stem from the
very study he has slated as being "at best bad science", namely the
Italian Register of children with HIV! He seems to want to both have his
cake and eat it.
1. HIV Trialists Collaborative Group. Zidovudine, didanosine and
zalcitabine in the treatment of HIV infection: meta-analysis of the
randomised evidence. Lancet 1999; 353: 2014-25
2. Staszewski S et al. Reductions in HIV-1 Disease progression for
zidovudine/lamivudine relative to control treatments: a meta-analysis of
controlled trials. AIDS 1997; 11:477-83.
3. Jordan R et al. Systematic review and meta-analysis of evidence
for increasing numbers of drugs in antiretroviral combination therapy. BMJ
2002; 324: 757-60.
Drug company sponsorship to attend HIV meetings
Competing interests: No competing interests
The McSherry paper(1) referred to has the conclusion:
Would they write such a thing if the study showed otherwise? Are you contesting that all the authors are self-medicating? Why would the editors and the review panel at the Journal of Pediatrics allow such a conclusion to be published if it wasn't supported by the findings?
Yet more unanswered questions.
Now McSherry joins Meles, Seligmann, Fleming, Padian, Phillips, McComsey, Pizzo and Gallo as authors (or authors of research) cited incorrectly to be in support of alternative AIDS theories.
(1) McSherry GD, Shapiro DE, Coombs RW, McGrath N, Frenkel LM, Britto P, Culnane M, Sperling RS. The effects of zidovudine in the subset of infants infected with human immunodeficiency virus type-1 (Pediatric AIDS Clinical Trials Group Protocol 076).
J Pediatr. 1999 Jun;134(6):717-24. [Abstract]
Competing interests: No competing interests
Peter Flegg says that I fail "to understand what is an appropriate
study to demonstrate clinical efficacy of a drug. I will say again, a
phase I/II safety/tolerability study is not designed to look at efficacy.
The fact that Rasnick fails to acknowledge this fact, and that he
persists in misrepresenting the trial data speaks volumes."
I understand completely the purposes of the three phases of
clinical trials. However, I can only work with what has been
published. I could not find (nor has Flegg cited) a completed or
even partial phase III clinical trial on the efficacy of anti-HIV drugs
in children. I ask Flegg: Where is that study? Where is the phase III
clinical trial that demonstrated that children taking the anti-HIV
drugs live longer or at least healthier lives than a similar group of
HIV-positive children not taking the drugs?
Failing to take his own advice, Flegg offers not a phase III, nor
even a phase I/II study, to argue for the life-saving benefits of the
anti-HIV drugs for children. Instead, the best he has come up with
is an observational study that spans 17 years (1980-1997) of the
AIDS epidemic in Italy . Flegg says that, "This longitudinal cohort
study of HIV in 1142 children demonstrated clearly that survival
improved with HIV therapy. In fact, the more drugs in combination
that children took, the better their prognosis (a finding that drives a
horse and cart through the dissidents' assertions that the drugs do
harm). The relative hazard of death declined with each extra drug
added into the combination as compared with no therapy (RH 0.29
for triple therapy)."
I have already provided ample evidence in the literature that the
anti-HIV drugs do considerable harm. The task now is to show, if
possible, that there are life-saving and other real clinical benefits
of the drugs that out weigh their well documented risks. With that in
mind, let's take a closer look at the de Martino et al. observational
study that spans a period that spawned four definitions of AIDS.
A decisive argument against this study proving any clinical benefit
whatever is that it was not a clinical trial designed to detect
potential clinical benefits of the drugs. A crucial point is that the
authors did not compare during the same period similar groups of
children taking the drugs and placebo. Instead, the authors used
the trick commonly employed by an AIDS establishment desperate
to justify claims that the anti-HIV drugs do more good than harm.
They compared the outcomes of three arbitrary groupings of
patients from different periods of the epidemic. This approach is
highly deceptive and is at best bad science. The authors state that,
"The [survival] estimates were calculated for birth cohort and
calendar period and grouped according to the distribution of
predominant type of antiretroviral therapy administered over time
(in part reflecting availability): 1980-1989 (reference group), 1990-
1995, and 1996-1998 (1996-1997 only for birth cohort because
those born later were excluded from this analysis)" . I use the
following parable to make clear the fallacy in the approach taken
by de Martino et al.
By arbitrarily comparing different periods of the epidemic one
could propose all sorts of nonsensical explanations for observed
correlations. For example, from 1980 to 1992, Republicans held
the presidency in the USA. This was the same period when AIDS
began in the USA and slowly increased to its peak in 1992 (see
cover of reference ). But, in 1992, a Democrat was elected
president and the AIDS epidemic immediately began to decline
and continued to do so through 2000, the end of Clinton's last term
in office. Ominously for this scenario, a Republican now occupies
the Whitehouse. It is still too soon to tell if there will be a rebound
in AIDS as a consequence.
Even though this farcical scenario is completely consistent with the
data, and shows a perfect correlation between political party and
direction of the AIDS epidemic, one would be foolish to conclude,
without further, more compelling evidence, that Republican
presidents promote AIDS while Democrats retard the epidemic.
Yet, in an analogous scenario we are encouraged to accept a
shaky (certainly unproved) explanation for a much poorer
correlation (almost no correlation, as shown below) between
survival of HIV-positive children and various periods in which
different antiretroviral drugs and combinations were in fashion.
Table 1 from the de Martino study shows that the number of HIV-
positive children reached a plateau from 1985 to 1992 and has
since declined steadily. This trend reflects the peaks in the various
AIDS epidemics for adults and children that were seen between
the late 1980s up to about 1995 all across Europe and the USA
(see especially Fig. 3 on page 43 of reference ).
In contrast with Flegg's assertions about what the de Martino et al.
study showed, the authors state that, "The probability of survival
did not significantly differ between the 1980-1989 and 1990-1995
birth cohorts (P=.15), whereas it was significantly higher for the
1996-1997 birth cohort... In evaluation of the calendar period
effect..., the cumulative probability of survival did not significantly
differ between children at risk in 1980-1989 and 1990-1995 (P=
.75), whereas probability of survival was significantly higher for
1996-1998...". The authors attributed the reduction in the mortality
of the 1996-1997 cohort and the 1996-1998 calendar period to the
introduction of triple combination antiretroviral cocktails, some of
which included the protease inhibitors or a nonnucleoside reverse
transcriptase inhibitor. But, Table 2 of the same paper seems to
erase the prospect that triple combination therapy prolonged the
lives of the Italian children. It shows that there was no significant
reduction in the adjusted relative hazards of death of the children
regardless of birth cohort or calendar period. Such shaky evidence
is not nearly as convincing to me as it apparently is to Flegg.
Even if one uncritically accepts the validity of the seriously flawed
de Martino et al. study, its own results clearly do not show any
beneficial effect on survival of the children who went from no drugs
to one anti-HIV drug, then two DNA-chain terminators, followed by
multiple combinations of two antiretroviral drugs. Yet we are
somehow expected to accept the magic number of three life-
saving antiretroviral drugs even though the evidence for them is
only two to three years old, compared to 9 years of evidence of no
life-saving benefits for one or various combinations of two drugs.
The authors conclude that, "Our study shows that although the
survival of HIV-infected children in Italy remained unchanged up to
1995, it has significantly improved since 1996, with a more than
30% reduction in the adjusted risk of death for children at risk in
the period 1996-1998 vs those at risk in the period 1980-1989."
But, since the authors state that, "57% of children were born to a
mother who was an injecting drug user or sexual partner of an
injecting drug user", there may be another explanation that the
authors did not consider. Were the children born to iv drug using
mothers equally distributed over the 17-year period under
consideration? Perhaps there were more such children in the
1980-1989 and 1990-1995 periods compared to the 1996-1998
period. If so, this could explain the reduced mortality in 1996-1998.
Almost any explanation is possible with an observational study
that spans 17 years, 4 definitions of AIDS, numerous changes in
therapies and heads of state.
Referring almost in passing to another study, Flegg says that
McSherry et al. showed that "26% of placebo-children progress[ed]
to AIDS compared with 14% of zidovudine-exposed children. The
actual numbers are small and immaterial in the context of this
discussion (even though they support my contention) ." Then
why bring it up?
Nevertheless, here's how McSherry et al. summed up their results
that Flegg says support his contention. "In this limited study,
zidovudine therapy during pregnancy and labor and in the
neonatal period for 6 weeks failed to have a major effect on rapid
progression of disease, timing of transmission, and viral replication
in HIV-infected infants." Given that conclusion, I say that the results
of the McSherry et al. better study support my contention than his.
1. de Martino, M., et al. (2000) Reduction in mortality with
availability of antiretroviral therapy for children with perinatal HIV-1
infection. Italian Register for HIV Infection in Children and the
Italian National AIDS Registry, Jama 284, 190-197
2. Centers for Disease Control and Prevention. (1997) U.S. HIV
and AIDS cases reported through December 1997; Year-end
edition, 9, 1-43
3. European Centre for the Epidemiological Monitoring of AIDS.
(2002) HIV/AIDS Surveillance in Europe: End-year report 2001,
No. 66, Saint-Maurice: Institut de Veille Sanitaire
4. McSherry, G. D., et al. (1999) The effects of zidovudine in the
subset of infants infected with human immunodeficiency virus type-
1 (Pediatric AIDS Clinical Trials Group Protocol 076), J Pediatr
Competing interests: No competing interests
David Rasnick (13th March,
http://bmj.com/cgi/eletters/326/7381/126/e#30342), yet again fails to
understand what is an appropriate study to demonstrate clinical efficacy
of a drug. I will say again, a phase I/II safety/tolerability study is not
designed to look at efficacy. The fact that Rasnick fails to acknowledge
this fact, and that he persists in misrepresenting the trial data speaks
He also takes me to task for not finding evidence that "anti-HIV
drugs actually prolong the lives, or at least improve the quality of the
lives, of the children given these drugs". I would like to point out that
I never offered to do his work for him, only pointing out that he was
looking in the wrong place. But since he wants evidence, perhaps I should
refer him back to the Italian Register of HIV infection in children, which
he cited in his earlier letter (1). This longitudinal cohort study of HIV
in 1142 children demonstrated clearly that survival improved with HIV
therapy. In fact, the more drugs in combination that children took, the
better their prognosis ( a finding that drives a horse and cart through
the dissidents' assertions that the drugs do harm). The relative hazard of
death declined with each extra drug added into the combination as compared
with no therapy (RH 0.29 for triple therapy).
Rasnick was unable to find my reference for lower progression rate
among HIV infected children exposed to perinatal zidovudine in the PACTG
076 trial. I apologise for giving the main trial authors as the source of
this information, in fact the relevant data are in a separate substudy of
PACT 076 (2). This showed 26% of placebo-children progressing to AIDS
compared with 14% of zidovudine-exposed children. The actual numbers are
small and immaterial in the context of this discussion (even though they
support my contention). The point I was making was that five randomised,
placebo-controlled controlled trials of perinatal zidovudine demonstrated
no evidence of harm in zidovudine recipients. Again, this is a fact
Rasnick seems willing to ignore, preferring to blame zidovudine toxicity
itself for reports in other studies where there has been more rapid
progression, even when the study authors do not take this view but give
alternative feasible explanations.
(1) Italian Register of HIV infection in Children. Reduction in
Mortality With Availability of Antiretroviral Therapy for Children With
Perinatal HIV-1 Infection.
JAMA, 2000; 284, pp. 190-197
(2) McSherry GD et al. The effects of zidovudine in the subset of
infants infected with human immunodeficiency virus type 1 (PACTG 076).
J Paediatr; 1999; 134; pp717-724
Attendance at HIV meetings with drug company sponsorship
Competing interests: No competing interests
Carl Williams' response 'Further comments on debate' raises a few questions (some of which are beyond my knowledge), however he does
make reference to a researcher that I have read of:
> ‘Evidence for exposure to HTLV-111 in Uganda before 1973.’ Science 227:1036-8. In that research, Robert Gallo and others reported
testing a number of sera from Uganda
I am not sure what this paper(1) from 1985 adds,
please feel free to let me know.
Much clearer are other findings by Robert Gallo. In his Historical Essay: The Early Years of HIV/AIDS(2), published in Science 2002:
various modes of HIV transmission were elucidated, all of HIV's genes and most of its proteins were defined, and the blood supply in most
developed nations was rendered safe as a result of screening for HIV."
many regions of the world."
(1) Saxinger WC, Levine PH, Dean AG, de The G, Lange-Wantzin G, Moghissi J, Laurent F, Hoh M, Sarngadharan MG, Gallo RC. Evidence for
exposure to HTLV-III in Uganda before 1973.
Science. 1985 Mar 1;227(4690):1036-8.
PMID: 2983417 [Abstract]
Competing interests: No competing interests
Further comments on debate
In my previous letter, I made various comments about
the use of emotive language and the unnecessarily
defensive tone employed in this debate. I also put
forward a suggestion as to a possible type of research
that, given the apparent circularity of the debate, might
further the discussion by elucidating results that are
unambiguous and irrefutable. I put forward this
suggestion because it is obviously difficult for either
side to conclusively prove the other side wrong by
reference to the currently available research.
It was my impression from reading the various
interchanges, that the personalities involved were at
times investing more energy attacking each other’s
right to a point of view, than addressing, in a
meaningful way, the contentious issues that were
being raised. Whilst I appreciate that scientists from
each side of the conventional/dissident fence might
feel a sense of frustration regarding the other’s point of
view, I cannot understand why this frustration should be
an impediment to debating the issues themselves in a
Speaking from a layperson’s perspective, the more
recent contributions, when focused on the issues
rather than on expressing disapprobation, have been a
lot more informative and engaging.
Whilst I agree that it may be entirely possible to explain
the different rates of disease prevalence across the
sub-Saharan continent by proposing different qualities,
or requisites for infectivity in various HIV clades, or sub-
types, as Jim Bond has suggested in a recent post on
a related HIV e-debate, I can also imagine the kinds
of arguments that might be proffered by David Rasnick
and others to explain the same epidemiological
phenomenon. This is why I have focused on what (to
all intents and purposes) appears to be a much
simpler question to answer and one that has a great
deal of significance to the HIV/AIDS knowledge base
(unless, of course, my logic has some inherent flaw
attached to it).
My suggestion is to re-examine stored sera for HIV
(using contemporary sera controls and a strictly
blinded protocol) as a means of establishing at least
one fact that is irrefutable and has potential
significance to modern treatment/prevention practices,
regardless of other disputes over HIV’s aetiology and
pathogenesis. This research would establish whether,
or not, HIV is a new phenomenon.
Given that HIV’s pathogenic effect remains seemingly
unstoppable, despite huge advances in medical
knowledge over the past 20 years and that it is
considered to be singularly responsible for the
suffering and deaths of so many individuals, the
presence, or absence of HIV in stored sera from
samples obtained prior to the ‘AIDS era’ should, I
would imagine, be something that would interest both
sides of the debate.
Although none of the contributors who responded to my
previous letter commented on the research I proposed,
Brian Foley e-mailed me several links and suggestions
to research that has already been done into the origins
of HIV prior to the ‘AIDS’ era, which was most helpful.
Brian informed me that this subject had already been
thoroughly researched stating: “In South Africa for
example HIV-1 seropositive blood samples were nearly
non-existant until the early 1990s. In the late 1980s to
1992 or so there were just a few cases of HIV infection
in South Africa, primarily HIV-1 subtype B virus among
white homosexual men.”
Although some of the research Brian suggested does
document instances of HIV in individuals who would
(by today’s criteria) be considered to have evidence of
AIDS, or AIDS defining illnesses, that research was
designed to document a specific relationship (with
inherent biases built in), rather than to look at the
instances of HIV in previous generations per se, which
was the point of the research I was suggesting.
Further searching has so far uncovered one piece of
research that supports the notion that my original
proposal was not entirely ridiculous, or naïve and also
appears to contradict what Brian Foley suggests to be
the case. Saxinger WC, Levine PH, Dean AG, et al
(1985). ‘Evidence for exposure to HTLV-111 in Uganda
before 1973.’ Science 227:1036-8. In that research,
Robert Gallo and others reported testing a number of
sera from Uganda that had been collected in 1972/73.
The sera were obtained from healthy children who took
part in a randomised study looking at Burkitt’s
lymphoma. Researcher’s performed both ELISA and
WB tests and 50 of 75 children (67%) were found to be
The mean age of the children involved was 6.4 years,
the children were presumably infected via vertical
transmission, and their mothers presumably acquired
their infections via heterosexual intercourse although
(in the absence of any conclusive proof to the contrary),
one can’t ignore the possibility that some of these may,
theoretically, have been vertically infected themselves -
by my calculations this would mean that in the late
1950’s to early 1960’s there was a significant number
of adults in just this one population who were infected
with HIV but were clearly surviving in good health into
adulthood without the benefits of treatment for HIV or
Another question seems to be posed by these
findings: Given that neither adults nor children were
treated for HIV/AIDS and the aforementioned
explanation for the spread of disease prevalence
across the sub-Saharan region by Jim Bond, I am
intrigued as to why the current epidemic did not occur
at least 20 years earlier?
It is really the first point that interests me - the presence
of HIV in seemingly healthy populations - because it is
quite separate from all the other issues that are the
subject of circular debate based on interpretations of
research findings. Mortimer et al, have made the
comment that, “Very few HIV-infected children are
surviving into adulthood in good health”. In the context
of this statement, I am interested in what other
contributors understand to be the significance of this
 HIV in Southern Africa: social and political factors
are very relevant, but so is the virus itself!, 3 March
2003 rapid e-mail response to The politics of AIDS in
South Africa: beyond the controversies Didier Fassin
and Helen Schneider BMJ 2003; 326: 495-497
Competing interests: No competing interests
I applaud Mr Richards for taking the hitherto rare tactic of standing by one of his references, rather than just changing the
topic and hoping that no-one will notice. For example, I have provided links above to articles by Meles, Seligmann, Fleming,
Padian, Phillips and McComsey, noting that not one of them appear to support any reason to doubt that HIV/AIDS is
transmissible and that antiretroviral drugs considerably extend the life of sufferers.
Does the Meles article(1),
as suggested, provide reason to throw any doubt upon the validity of current HIV diagnosis?
I do know that a total of 12,124 specimens were tested for HIV-1 antibodies. 31 WB assays were found to be indeterminate.
Does pointing to variability amongst this 0.0026% raise an issue anyway??? Have any of the authors of the paper drawn any
conclusions from this? If not, why not? I've found numerous more research articles by several of the authors - none of them
have raised concerns over the accuracy of their tests.
Can you blame me for being sceptical given the plethora of other errors in attempts to support alternative AIDS theories?
A fine example of someone twisting numbers to attempt prove a point (or hoping that nobody will check the source):
In a response with the extraordinary title "HIV drugs fail in children" (27th February 2003) the following statement is made:
improvement, was present at the time of death...
That is the ultimate example of "the operation was a success but the patient died" cliché.
Sometimes people die in ambulances. Is that a reason to conclude that all ambulances should be banned?
The article cited in support of that statement(2) is available on line.
It states that:
that IQ scores, including those for verbal and performance IQ, rose
immunoglobulin levels, and increased numbers of CD4 cells.
And these results were whilst using ONLY AZT 15 Years ago!!!
A much more recent study by Bhana and
colleagues(2) found that:
therapy for the treatment of pediatric HIV infection as significant and sustained reductions in viral load have been shown in
both plasma and cerebrospinal fluid.
So Pizzo is now added to the list of authors falsely cited in support of alternative AIDS arguments. And to think I only
entered this (alleged) debate after taking notice of Brian Foley's statement 'we both can't be right', and then checking the
original references to see who was telling fibs.
(1) Meles H, Wolday D, Fontanet A, Tsegaye A, Tilahun T, Aklilu M, Sanders E, De Wit TF. Indeterminate human immunodeficiency
virus Western blot profiles in ethiopians with discordant screening-assay results.
Clin Diagn Lab Immunol. 2002 Jan;9(1):160-3.
(2) Pizzo PA, Eddy J, Falloon J, Balis FM, Murphy RF, Moss H, Wolters P, Brouwers P, Jarosinski P, Rubin M, et al. Effect of
continuous intravenous infusion of zidovudine (AZT) in children with symptomatic HIV infection.
N Engl J Med. 1988 Oct 6;319(14):889-96.
PMID: 3166511 [Abstract]
(3) Bhana N, Ormrod D, Perry CM, Figgitt DP. Zidovudine: a review of its use in the management of vertically-acquired
pediatric HIV infection.
Paediatr Drugs. 2002;4(8):515-53. Review.
PMID: 12126455 [Abstract]
Competing interests: No competing interests
Re: Doctor Meles. Yet another researcher incorrectly cited in support of alternative AIDS theories..
Tony Floyd suggests the reason I cite results from a study by Meles
H, et al. (1) is to "throw doubt upon the validity of current HIV
diagnosis." Ignoring for the moment that the tests used to diagnose
infection with HIV are not validated or approved for that purpose in the
first place, I specifically cited data from Meles et al study only to
demonstrate that different institutional criteria for scoring Western Blot
(WB) lead to different conclusions of who should be told they are
infected. The observation in this study that 19.4% of persons considered
indeterminate by one criterion (American Red Cross) are considered
positive by another criterion (CDC) leaves no doubt that this is the case.
The coincidental observation that all of these individuals were deemed to
be "uninfected" on follow-up testing, which they would have never received
in the USA, is alarming and unacceptable.
Floyd questions the significance of the discrepancy revealed in this
study because there were only "31 initially indeterminate results out of a
total of 1 437 [antibody positive] study participants." He goes on to
emphasize that this means, "97.84% of [these] results were NOT
indeterminate." The implication being, why am I trying to generalize
conclusions from these 31 samples when they represent only about 2% of the
total HIV positive designations? Why not focus on the other 98% that were
"NOT indeterminate?" There is a very good reason for this. The 31
samples in this study are the only samples for which both WB and follow-up
data are reported (actually, there were a total of 91 indeterminate
results, however, follow-up data was available for only 31 of these
samples). The vast majority of the remaining samples considered to be HIV
positive in this study were never even subjected to WB testing, let alone
The reason for this is that according to currently accepted standards
of practice put forth by the WHO and UNAIDS, (2) samples that test
positive on each of two screening assays in Africa can be declared
infected without confirmation of banding patterns by WB. Only in cases
where the initial screening assays are discordant (one positive and one
negative) are samples routinely subjected to WB testing (or in some cases,
a third screening assay). The 91 indeterminate results reported in this
study arose from such discordant screening assays. The remaining samples
scored positive on two screening assays and were therefore considered
unequivocally infected without the need for WB confirmation. As such, we
will never know how many of these other samples might have tested
negative, positive, or indeterminate on WB; let alone how their banding
patterns might have changed over time. (3)
Perhaps a better way to summarize the data in the Meles et al. study
is as follows: Of all persons found to have antibodies to HIV specific
antigens on WB, and for whom follow-up testing was available, 93.5% became
negative when retested while 6.5% remained indeterminate for more than a
year and were thus considered negative. Had the CDC criteria been used,
nearly 20% of these individuals would have been declared unequivocally
infected and never retested.
Granted the sample size in this study is small, and the confidence
intervals are likely to be wide. Nevertheless, this is one of the few
studies that present any follow-up data for changes in WB patterns over
time. The true significance of the observations in this study lies in how
many individuals might be expected to test indeterminate (or positive by
someone else's criteria) in the first place.
Researchers are well aware that indeterminate WB results in Africa
are anything but anecdotal. The Meles et al. publication itself
emphasizes, "indeterminate WB profiles in HIV-uninfected subjects are
frequent and are as high as 23 to 53% in some African populations." (1)
According to the authors of another recent study in Uganda, "Western blot
(WB) criteria in epidemiological studies in Africa exhibit an unacceptably
high proportion of indeterminate results." (4) The authors of this study
go on to demonstrate that the WHO and CDC criteria correctly classified
only 57.6% and 57.8% of their study population, respectively.
Furthermore, using their own algorithm as the gold standard, they
calculate the specificity of the WHO and CDC criteria to be only 53.1%.
This is slightly better than a coin flip.
Depending on the study and which WB criteria is embraced to represent
the truth, anywhere from about 10% to 40% of African samples that are
initially positive for antibodies on one or more screening assay can be
expected to test indeterminate on WB. In other words, about 10 to 40% of
samples considered to be positive for HIV using screening assays in Africa
cannot be confirmed positive using WB. The reason we rarely hear about
this data is because Africans are never subjected to WB testing in routine
practice; and even in cases where WB is performed, such as validation
studies for new test kits, all indeterminate samples are conveniently
excluded from calculations of test kit accuracies.
Even more remarkably, depending on the study and the health of
individuals, approximately 20 to 90% of ELISA negative individuals in
Africa can be expected to test indeterminate on WB. For example, in one
study (5) using blood collected in Tanzania, of 89 samples found to be
negative on all of four different recombinant ELISA kits, 27 (30.3%)
tested positive on WB for one or more HIV specific band. Furthermore,
among those seeking care (i.e., sick) the percentage went up to 50%. In
another study conducted at the Uganda Virus Research Institute, (6)
researchers evaluated WB patterns among ELISA negative rural Africans with
various illnesses; 57% of healthy controls, 79% with hookworm, 81% with
malaria, and 84% with bacterial infections, were found to be positive on
WB for one or more viral specific band. Remarkably, 10% (2/21) of the
healthy ELISA negative controls in this study actually tested WB positive
according to the CDC criteria.
It is important to remember the only thing that distinguishes
individuals as having non-specific antibody reactions, or cross-reacting
antibodies due to manageable infections, rather than HIV infection, is an
arbitrarily selected WB criterion that designates them indeterminate
rather than positive. As soon as an individual exhibits the magic
combination of bands held out to represent infection in their locality,
their antibodies are perceived to be specific and they are told they are
infected with a deadly virus. Instead of considering the possibility that
those with illnesses such as bacterial infections may have false positive
designations due to cross-reacting antibodies (as illustrated above), the
bacterial infection is instead blamed on HIV, and the individual is told
they have Stage III HIV disease.
The reality that persons are told they are infected with HIV based on
results from tests that have not been validated or approved for this
purpose is unacceptable on its own accord. The fact that various
institutional criteria lead to different conclusions as to who is
inappropriately told they are infected is further objectionable. The
observation in the Meles et al. study that 93.5% of persons initially
positive for antibodies to HIV specific antigens on WB became negative on
follow-up testing is irrelevant to the fact that these tests are being
misused in the first place; however, in my opinion this does indeed "throw
[further] doubt upon the validity of current HIV diagnosis."
1. Meles H, et al. Clin Diagn Lab Immunol 2002; 9:160-3.
2. WHO. Wkly Epidemiol Rec 1997; 72: 81-8.
3. Actually, one of the "several" cohorts included in this study did
require WB confirmation of samples testing concordantly positive on two
ELISA screening assays; however, based on available published data (Sahlu
T, et al. J Acquir Immune Defic Syndr Hum Retrovirol 1998; 17:149-55;
Sahlu T, et al. AIDS 1999; 13: 1263-72.) for this study, fewer than 150 of
the 1,437 positive screening result reported in the Meles et al study
would have fallen into this category. Furthermore, there is no follow-up
data for these individuals to indicate how their WB profiles may have
changed over time.
4. Mahe C, et al. International Journal of Epidemiology 2002; 31:985-
5. Christianseen CB, et al. AIDS 1990; 4:1039-40.
6. Medical Research Council (UK), Dept for International Development
(UK), Uganda Virus Research Institute, PO Box 49, Entebbe, Uganda.
Programme on AIDS in Uganda 1999; Annual Report.
Competing interests: No competing interests
Zidovudine was shown to decrease mother to infant transmission of HIV by approximately two thirds...
Both Peter Flegg (11th March 2003) and David Rasnick (13th March 2003), have referenced work by Doctor Edward Connor from the New Jersey Medical School. They have both cited the same paper (available on line here).
The findings are:
Perhaps either of you would like to advise what else could be concluded from this? Or was one of you assuming that nobody would bother checking the actual article???
(1) Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.
N Engl J Med. 1994 Nov 3;331(18):1173-80. [Abstract]
Competing interests: No competing interests