BMJ 2001;322:1226-1229 ( 19 May )

Clinical review

ABC of AIDS

Development of the epidemic

Michael W Adler. 

The first recognised cases of the acquired immune deficiency syndrome (AIDS) occurred in the summer of 1981 in America. Reports began to appear of Pneumocystis carinii pneumonia and Kaposi's sarcoma in young men, who it was subsequently realised were both homosexual and immunocompromised. Even though the condition became known early on as AIDS, its cause and modes of transmission were not immediately obvious. The virus now known to cause AIDS in a proportion of those infected was discovered in 1983 and given various names. The internationally accepted term is now the human immunodeficiency virus (HIV). Subsequently a new variant has been isolated in patients with West African connections---HIV-2.


This article has been adapted from the forthcoming 5th edition of ABC of AIDS. The book will be available from the BMJ bookshop and at www.bmjbooks.com


AIDS defining conditions without laboratory evidence of HIV

  • Diseases diagnosed definitely
  • Candidiasis: oesophagus, trachea, bronchi, or lungs
  • Cryptococcosis: extrapulmonary
  • Cryptosporidiosis with diarrhoea persisting >1 month
  • Cytomegalovirus disease other than in liver, spleen, nodes
  • Herpes simplex virus (HSV) infection
      Mucocutaneous ulceration lasting >1 month
      Pulmonary, oesophageal involvement
  • Kaposi's sarcoma in patient <60 years of age
  • Primary cerebral lymphoma in patient <60 years of age
  • Lymphoid interstitial pneumonia in child <13 years of age
  • Mycobacterium avium: disseminated
  • Mycobacterium kansasii: disseminated
  • Pneumocystis carinii pneumonia
  • Progressive multifocal leucoencephalopathy
  • Cerebral toxoplasmosis

The definition of AIDS has changed over the years as a result of an increasing appreciation of the wide spectrum of clinical manifestations of infection with HIV. Currently, AIDS is defined as an illness characterised by one or more indicator diseases. In the absence of another cause of immune deficiency and without laboratory evidence of HIV infection (if the patient has not been tested or the results are inconclusive), certain diseases when definitively diagnosed are indicative of AIDS. Also, regardless of the presence of other causes of immune deficiency, if there is laboratory evidence of HIV infection, other indicator diseases that require a definitive, or in some cases only a presumptive, diagnosis also constitute a diagnosis of AIDS.

In 1993 the Centers for Disease Control (CDC) in the USA extended the definition of AIDS to include all persons who are severely immunosuppressed (a CD4 count <200×106 cells/l) irrespective of the presence or absence of an indicator disease. For surveillance purposes this definition has not been accepted within the UK and Europe. In these countries AIDS continues to be a clinical diagnosis defined by one or more of the indicator diseases mentioned. The World Health Organization (WHO) also uses this clinically based definition for surveillance within developed countries. WHO, however, has developed an alternative case definition for use in sub-Saharan Africa. This is based on clinical signs and does not require laboratory confirmation of infection. Subsequently this definition has been modified to include a positive test for HIV antibody.


AIDS defining conditions with laboratory evidence of HIV

Diseases diagnosed definitely

  • Recurrent/multiple bacterial infections in child <13 years of age
  • Coccidiomycosis---disseminated
  • HIV encephalopathy
  • Histoplasmosis---disseminated
  • Isosporiasis with diarrhoea persisting >1 month
  • Kaposi's sarcoma at any age
  • Primary cerebral lymphoma: at any age
  • Non-Hodgkin's lymphoma: diffuse, undifferentiated B cell type, or unknown phenotype
  • Any disseminated myobacterial disease other than M tuberculosis
  • Mycobacterial tuberculosis
  • Salmonella septicaemia: recurrent
  • HIV wasting syndrome
  • Recurrent pneumonia within 1 year
  • Invasive cervical cancer

Diseases diagnosed presumptively

  • Candidiasis: oesophagus
  • Cytomegalovirus retinitis with visual loss
  • Kaposi's sarcoma
  • Mycobacterial disease (acid-fast bacilli; species not identified by culture): disseminated
  • Pneumocystis carinii pneumonia
  • Cerebral toxoplasmosis

These case definitions are complex and any clinician who is unfamiliar with diagnosing AIDS should study the documents describing them in detail.


HIV Transmission: global summary


Type of exposure Percentage of global total
Blood transfusion 3-5
Perinatal 5-10
Sexual intercourse 70-80
  (vaginal) (60-70)
  (anal) (5-10)
Injecting drug use (sharing needles, etc) 5-10
Health care (needlestick injury, etc) <0.01




    Transmission of the virus
Top
Transmission of the virus
Growth and size of...

HIV has been isolated from semen, cervical secretions, lymphocytes, cell-free plasma, cerebrospinal fluid, tears, saliva, urine, and breast milk. This does not mean, however, that these fluids all transmit infection since the concentration of virus in them varies considerably. Particularly infectious are semen, blood, and possibly cervical secretions. The commonest mode of transmission of the virus throughout the world is by sexual intercourse. Whether this is anal or vaginal is unimportant. Other methods of transmission are through the receipt of infected blood or blood products, donated organs, and semen. Transmission also occurs through the sharing or reuse of contaminated needles by injecting drug users or for therapeutic procedures, and from mother to child. Transmission from mother to child occurs in utero and also possibly at birth. Finally, the virus is transmitted through breast milk.


Transmission of the virus

  • Sexual intercourse
    Anal and vaginal
  • Contaminated needles
    Injecting drug users
    Needlestick injuries
    Injections
  • Mother right-arrow child
    In utero
    At birth
    Breast milk
  • Organ/tissue donation
    Semen
    Kidneys
    Skin, bone marrow, corneas, heart valves, tendons, etc

The virus is not spread by casual or social contact. Health care workers can, however, be infected through needlestick injuries, and skin and mucosal exposure to infected blood or body fluids. Prospective studies in health care workers suffering percutaneous exposure to a known HIV seropositive patient indicate a transmission rate of 0.32%. As of December 1999 there have been 96 reported cases of documented seroconversion after occupational exposure in such workers.

The precautions and risks for such groups are covered in detail in chapter 15. Finally, there is no evidence that the virus is spread by mosquitoes, lice, bed bugs, in swimming pools, or by sharing cups, eating and cooking utensils, toilets, and air space with an infected individual. Hence, HIV infection and AIDS are not contagious.


    Growth and size of the epidemic
Top
Transmission of the virus
Growth and size of...

Even though North America and Europe experienced the first impact of the epidemic, infections with HIV are now seen throughout the world, and the major focus of the epidemic is in developing/resource-poor countries.

Worldwide
The joint United Nations programme on AIDS (UNAIDS) has estimated that by the end of 1999 there were 34.3 million people living with HIV/AIDS (33.0 million adults and 1.3 million children <15 years). The new infections during that year were 5.4 million, approximately 15 000 new infections per day.


Regional HIV/AIDS statistics and features, end of 2000


Region Epidemic started Adults and children living with HIV/AIDS Adults and children newly infected with HIV Adult prevalence rate* % of HIV positive adults who are women Main mode(s) of transmissiondagger for adults living with HIV/AIDS
Sub-Saharan Africa late 1970s to early 1980s 25.3 million 3.8 million 8.8% 55% Hetero
North Africa and Middle East late 1980s 400 000  80 000 0.2% 40% Hetero, IDU
South and South East Asia late 1980s  5.8 million 780 000 0.56% 35% Hetero, IDU
East Asia and Pacific late 1980s 640 000 130 000 0.07% 13% IDU, hetero, MSM
Latin America late 1970s to early 1980s  1.4 million 150 000 0.5% 25% MSM, IDU, hetero
Caribbean late 1970s to early 1980s 390 000  60 000 2.3% 35% Hetero, MSM
Eastern Europe and Central Asia early 1990s 700 000 250 000 0.35% 25% IDU
Western Europe late 1970s to early 1980s 540 000  30 000 0.24% 25% MSM, IDU
North America late 1970s to early 1980s 920 000  45 000 0.6% 20% MSM, IDU, hetero
Australia and New Zealand late 1970s to early 1980s  15 000    500 0.13% 10% MSM
Total 36.1 million 5.3 million 1.1% 47%

*The proportion of adults (15-49 years of age) living with HIV/AIDS in 2000, using 2000 population numbers. dagger Hetero=heterosexual transmission; IDU=transmission through injecting drug use; MSM=sexual transmission among men who have sex with men.

Currently, 95% of all infections occur in developing countries and continents, the major brunt of the epidemic being seen in sub-Saharan Africa and South East Asia. It is now recognised that cases of AIDS were first seen in Central Africa in the 1970s even though at that time it was not recognised as such. Current surveys from some African countries show that the prevalence of infection is high amongst certain groups--- 50-90% of prostitutes, up to 60-70% of those attending departments for sexually transmitted diseases and antenatal clinics. In the developing world, HIV is spread mainly by heterosexual intercourse.



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  		Prevalence of HIV---different groups

At a family level, UNAIDS estimates that by the end of 1999 the epidemic has left behind a cumulative total of 13.2 million AIDS orphans (defined as those having lost their mother or both parents to AIDS before reaching the age of 15 years). Many of these maternal orphans have also lost their father. Orphans in Zimbabwe are expected to total 1 million by 2005 and 2 million in South Africa by 2010. Traditional family structures and extended families are breaking down under the strain of HIV. Population growth and death rates are increasingly affected. Life expectancy in countries with adult prevalences of over 10% (for example, Botswana, Kenya, Zimbabwe, South Africa, Zambia, Rwanda) are expected to see an average reduction in life expectancy of 17 years by 2010-2015. Young, highly productive adults die at the peak of their output, which has a considerable impact on a country's economy.

USA, UK and Europe
By June 1999, 702 748 adult cases of AIDS had been reported in the USA. In addition there were 8596 paediatric cases (<13 years old). Most of the cases in children (91%) occur because a patient suffered from HIV or belonged to a group at increased risk of HIV; 4% occurred through blood transfusion; 3% in children with haemophilia. Information on risk factors for the remaining 2% of the parents of these children is not complete.

Adult cases in Europe totalled 224 359 by June 1999, and those in the UK 12 780. There are five times more people infected with HIV at any one time than have AIDS. The rate for AIDS cases varies throughout Europe, with particularly high rates in Italy, Portugal, Spain, France and Switzerland, where the commonest mode of infection is through injecting drug use and the sharing of needles and equipment.

In North America and the UK the first wave of the epidemic occurred in homosexual men. In the UK, proportionally more homosexual men have been notified than in America: 66% of cases compared with 48% respectively. Even though infections amongst men who have sex with men still arise, an increasing proportion of new infections in the USA is occurring amongst injecting drug users sharing needles and equipment. There is also an increase amongst heterosexuals in both the USA and the UK. Currently in the USA, 16% of cases of AIDS have occurred amongst women, and although the commonest risk factor amongst such women is injecting drug use (42%), the next most common mode of transmission is heterosexual contact (40%).



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  		AIDS in Europe---top ten countries 1999

The nature of the epidemic within the UK is changing with more heterosexual transmission. In the UK 12% of adult cases of AIDS have occurred in women, 70% of which have resulted from heterosexual intercourse. In 1999 there were more new annual infections of HIV than ever before and for the first time more occurring as a result of heterosexual sex than men having sex with men. Most heterosexually acquired infections are seen in men and women who have come from or have spent time in sub-Saharan Africa.

The advent of an antibody test in 1984 has allowed for a clearer understanding of the changing prevalence and natural history of HIV infection. Surveys show that the proportion of individuals infected needs to be high before cases of AIDS start to become apparent. It also underlines the importance of health education campaigns early in the epidemic, when the seroprevalence of HIV is low. Once cases of AIDS start to appear the epidemic drives itself and a much greater effort is required in terms of control and medical care.

Within countries one finds considerable variation in seroprevalence levels for HIV. Over 70% of cases of AIDS and HIV infection within the UK occur and are seen in the Thames regions (London and the surrounding area). Among different groups one also finds geographic differences. For example, the rates among drug users is higher in Edinburgh than London, and for gay men higher in London than anywhere else in the UK. This is also found in the developing world---for example, in Tanzania and Uganda, the urban level of HIV infection in men and women can be five times higher than rural rates.



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  		HIV infected individuals diagnosed in the UK by exposure category: to end of 1999

The use of highly active antiretroviral therapy in resource-rich countries has resulted in an increase in life expectancy. This, in combination with the increase in new HIV infections, means that the prevalent pool of those infected, and potentially infectious, is increasing. This presents a continuing challenge for health promotion and a re-statement of the importance of safe sex techniques, particularly condom use.


AIDS: adult patient groups in the USA and UK


Patient groups USA (June 99)
 UK (Dec 99)
n % n %
Men who have sex with men 334 073  48 11 063  66
Intravenous drug user 179 228  26  1 065   6
Men who have sex with man and IV drug user  45 266   6    293   2
Received blood/haemophilia  13 440   2    813   5
Heterosexual contact  70 582  10  3 049  18
Mother to infant    349   2
Other/undetermined  60 159   8    174   1
Total 702 748 100 16 806 100

AIDS results in a considerable cost not only in human suffering, but also to health services. Other costs include time off work and the effect of the deaths of young people on national productivity. AIDS represents a major public health problem in the world. A clear understanding of the epidemiology forms the basis of developing a strategy or control ranging from health education to research.


The data on AIDS/HIV in the UK is reproduced with permission from the Communicable Disease Surveillance Centre (CDSC) and the United Nations AIDS Programme.



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