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HIV and related viruses

HIV was discovered by Barré-Sinoussi, Montagnier, and colleagues at the Institut Pasteur, Paris, in 1983 and given the name lymphadenopathy associated virus (LAV). In 1984 Popovic, Gallo, and co-workers described the development of cell lines permanently and productively infected with the virus. In line with two previously described retroviruses, HTLV-I and HTLV-II, they designated this virus HTLV-III. Other virus isolates from patients with AIDS and AIDS-related disease in America, Europe and Central Africa have proved to be all the same virus, now referred to as HIV-1. Eight subtypes of HIV-1, alphabetically designated, have so far been described.

Around 1985 another human retrovirus, different from HIV- 1, was recognised in patients from West Africa. This virus, referred to by the Paris investigators as LAV-2 and more recently as HIV-2, is also associated with human AIDS and AIDS-related disease. It is closely related to the simian retrovirus, SIV, carried by healthy African green monkeys, and the cause of an AIDS-like disease in captive rhesus monkeys. Though potentially important worldwide, HIV-2 infections remain uncommon outside West Africa and they have proved far less virulent than HIV-1 infections.

The Virus and the Test

Although it is clear that HIV is the underlying cause of AIDS and AIDS-related disease, its origin remains obscure. There is firm serological evidence of infection on the east and west coasts of the USA from the mid 1970s, and HIV infection in central Africa may have antedated infection in North America.

Phylogenetic analysis of the HIV-1 genome has suggested an origin in chimpanzees while, in the case of HIV-2, similarity to the simian immunodeficiency virus (SIV) genome may point to an origin in sooty mangabey monkeys. In both cases the butchery and consumption of these “bush meats” has been incriminated in transmissions to the human host. Like some other RNA viruses, HIV appears to have mutated and shifted its host range and virulence, explaining how a new pathogenic retrovirus could arise in man. Its virulence may since have been amplified as a result of travel, population dislocation and promiscuous sexual contact, with rapid passage of the virus.

Retroviruses are so named because their genomes encode an unusual enzyme, reverse transcriptase, which allows DNA to be transcribed from RNA. Thus, HIV can make copies of its own genome, as DNA, in host cells such as the human CD4 “helper” lymphocyte. The viral DNA becomes integrated in the lymphocyte genome, and this is the basis for chronic HIV infection. Integration of the HIV genome into host cells is a formidable obstacle to any antiviral treatment that would not just suppress but also eradicate the infection. Nevertheless, modern treatment with combinations of nucleoside analogues and protease inhibitors has transformed the prognosis for carriers of HIV, usually achieving a sustained fall in virus concentration in blood and restoration of the main target cell (CD4 lymphocyte) to near normal levels.

By contrast, the inherent variability of the HIV genome and the failure of the human host to produce neutralising antibodies to the virus, as well as technical difficulties and concerns about safety, have continued to frustrate attempts to make an effective vaccine. This must not, however, allow efforts to develop and evaluate candidate vaccines to slacken. A particular concern is that a useful candidate vaccine (probably a recombinant envelope vaccine developed in North America or Europe against the locally prevalent HIV-1 B subtype) would be ineffective in those parts of the world where other subtypes predominate.

WHO estimates that in the year 2000 there are 36 million carriers of HIV worldwide, and only a small fraction of them have access to suppressive treatment. Both their contacts, their dependants and possibly they themselves would have their life prospects transformed by an effective, or even partially effective, vaccine, and successful application of antiviral treatment in developed countries should in no way be allowed to deflect attention from the necessity of developing and delivering an effective vaccine and of promoting “safe sex” behaviour.

USA, UK and Europe , Growth and size of the epidemic

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 234 406 by June 2000, and those in the UK 17 151 (December 2000). 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 intravenous 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: 67% 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 intravenous 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%).

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 2000 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 effective 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 geographical 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. The use of highly active antiretroviral therapy (HAART) 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.

Worldwide Growth and size of the epidemic

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.

The joint United Nations programme on AIDS (UNAIDS) has estimated that by the end of 2000 there were 36.1 million people living with HIV/AIDS (34.7 million adults and 1.4 million children <15 years). The new infections during that year were 5.3 million, approximately 16,000 new infections per day.

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.

At a family level, UNAIDS estimated that by the end of 1999 the epidemic had 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.

Transmission of AIDS

Sexual intercourse
  • anal and vaginal
Contaminated needles
  • intravenous drug users
  • needlestick injuries
  • injections
Mother . child
  • in utero
  • at birth
  • breast milk
Organ/tissue donation
  • semen
  • kidneys
  • skin, bone marrow, corneas, heart valves, tendons etc.

Transmission of the virus

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.

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.

AIDS-defining conditions with laboratory evidence of HIV

  • Diseases diagnosed definitively
  • Recurrent/multiple bacterial infections in child <13>
  • 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 mycobacterial disease other than M. tuberculosis
  • Mycobacterial tuberculosis at any site
  • 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

AIDS-defining conditions without laboratory evidence of HIV

  • Diseases diagnosed definitively
  • 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>
  • Primary cerebral lymphoma in patient <60>
  • Lymphoid interstitial pneumonia in child <13>
  • Mycobacterium avium: disseminated
  • Mycobacterium kansasii: disseminated
  • Pneumocystis carinii pneumonia
  • Progressive multifocal leukoencephalopathy
  • Cerebral toxoplasmosis

Early history of the epidemic

1981 Cases of Pneumocystis carinii pneumonia and Kaposi’s sarcoma in the USA
1983 Discovery of the virus. First cases of AIDS in the UK
1984 Development of antibody test

Development of the Epidemic

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 neumonia and Kaposi’s sarcoma in young men, who it was subsequently realised were both omosexual 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.

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 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 Organisation (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 onfirmation of infection. Subsequently this definition has been modified to include a positive test for HIV antibody.