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Keywords:

  • epidemiology;
  • HIV;
  • origin;
  • prevention;
  • socioeconomic consequences;
  • treatments

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Biomedical overview
  5. Epidemiology
  6. Social and political aspects
  7. Denial, disinformation and misconceptions
  8. Discussion
  9. Conflict of interest statement
  10. References

Science responded to the challenge of AIDS by rapidly identifying aetiology, describing pathogenesis and transmission routes, and developing diagnostic tests and treatment. However, this did not prevent the global spread of HIV, with 25 million fatal cases so far, another 33 million infected, and disastrous socioeconomic and demographic consequences. In spite of unprecedented political attention and financial resources, the response is falling further behind the growth of the epidemic. This is partly due to the unique characteristics of the virus, such as persistent infection, vertical transmission and a variability that allows it to escape immunity and antiretroviral drugs, and partly due to human characteristics such as a strong procreative instinct, drug use and ostracism. Denial, myths and complacency are major obstacles to rational measures. With no cure or vaccine in sight, scaling up prevention is of paramount importance. To meet the goal of universal access to prevention, treatment and care by 2010 would require a quadrupling of funding to an estimated US$42 billion by 2010, including adequate overall strengthening of healthcare systems, but in any case, the world will have to learn to live with HIV for the foreseeable future.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Biomedical overview
  5. Epidemiology
  6. Social and political aspects
  7. Denial, disinformation and misconceptions
  8. Discussion
  9. Conflict of interest statement
  10. References

AIDS took the world by surprise. It seemed to a confident world that infectious diseases could be conquered by vaccinations and antibiotics, and when AIDS came, it was taken for granted that modern science would soon avert this threat. This did not happen, and a number of other threats have since helped to make us slightly more humble: SARS, bird flu and mad-cow disease, to name a few.

AIDS has provoked panic, stigmatization and scapegoat-finding in the same way as other plagues of historical dimension, but in many ways it is different. It is caused by a persistent infection and has a silent period of many years between infection to the onset of serious symptoms. HIV is integrated into the very genome of the cells it attacks. Therefore, in contrast to other major epidemics, the AIDS epidemic has no rapid rise, obvious peak, or rapid decline. It targets people in productive ages, strong young adults, which has serious economic, political, demographic consequences. It is 100% fatal without life-long treatment with antiretroviral drugs. It is sexually transmitted, and such infections are renowned for being difficult to control, even when treatment is available. It is also transmitted vertically, from mother to child. The subject of AIDS is emotionally and politically charged, and denial has frequently prevented rational countermeasures. Activists and nongovernmental organizations have therefore played an important role. Due to the threat it poses to the very fabric of society, AIDS has received unique attention from world bodies such as the UN General Assembly and Security Council, and has attracted larger financial resources than is usual for public health concerns. AIDS has also spearheaded biomedical and behavioural research, and put the limelight on discrimination and social problems.

This is an account of the first 25 years of HIV/AIDS, and is intended to give a collected view of the vastness and many dimensions of the epidemic.

Biomedical overview

  1. Top of page
  2. Abstract
  3. Introduction
  4. Biomedical overview
  5. Epidemiology
  6. Social and political aspects
  7. Denial, disinformation and misconceptions
  8. Discussion
  9. Conflict of interest statement
  10. References

The long road to proving that retroviruses are pathogenic in humans

AIDS research is a success story from the natural science point of view. The disease was described in 1981, the new retrovirus was reported to have been found in tissues from AIDS patients in 1983, the causative relationship between this virus and AIDS was established in 1984 and in 1985, tests for HIV were commercially available – a new record. Similarly, new drugs became available in an amazingly short time. However, these rapid advances were not the result of a single stroke of genius, but rather the product of decades of laborious scientific work and tools developed in molecular biological research.

Two key clues that aided researchers in identifying the cause behind the new disease were the epidemiological evidence that the disease was caused by an infectious agent with risk factors similar to those for syphilis, and the combination of immune suppression, tumours and opportunistic diseases. These factors corresponded with experience from certain retroviruses.

A link between retroviruses and tumours was first demonstrated in 1910, when Peyton Rous showed that chicken sarcoma could be transmitted to healthy chickens via a cell-free extract. Rous was awarded the Nobel Prize in 1966 (at the age of 86!) for his discovery. Later, transmissible viruses were demonstrated in leukaemia in chickens, mice and cattle. Retroviruses were also reported to cause infectious leukaemia in nonhuman primates. An important discovery for HIV research was made during the early 1960s by William Jarrett [1, 2], who identified the feline leukaemia virus, which causes not only leukaemia but also immune deficiency and symptoms characteristic of AIDS. The findings were confirmed by Max Essex’ group [3], who showed that the virus could be spread by sexual intercourse, and that the notoriously promiscuous tomcats were at particular risk of acquiring the virus and developing AIDS-like symptoms.

Thus animal studies demonstrated that tumours and immune deficiency could be caused by contagious retroviruses. However, the idea was controversial, as theories on the mechanisms whereby retroviruses could cause tumours were difficult to confirm. The retrovirus causing Rous’ sarcoma, for example, incorporated a new gene from the DNA of an infected cell during the course of transmission. This oncogene gave the virus the ability to transform normal cells to tumour cells, but this is a very rare event; such viruses are usually defective. Neither could the virogene–oncogene hypothesis [4] be confirmed, which proposed that tumours originate when endogenous retroviruses (which comprise approximately 8% of our genome, [5]) are activated. Activation of endogenous retroviruses did not cause tumours, and tumours were induced without such activation. The theory of retroviruses causing tumours therefore lost favour, and many scientists considered them ‘innocent bystanders’. Such scepticism might linger behind doubts regarding the causal association between HIV and AIDS, even if the association is long-since scientifically proven.

Thus when Robert Gallo at the NIH devoted tedious research in the 1970s to hunting for tumour viruses in humans, he was sometimes ridiculed by colleagues who referred to them as ‘rumour viruses’. Gallo’s work was particularly aimed at culturing lymphocytes in cell cultures, and in 1980 his group finally published the discovery of Human T-cell Leukaemia Virus (HTLV), the first tumour-causing retrovirus to affect humans [6]. Immune deficiency is a characteristic feature of HTLV infection. A second retrovirus dubbed HTLV-2 was detected in humans in1982 [7]; it causes hairy cell leukaemia.

Human T-cell Leukaemia Virus cases often originated in the Caribbean, but clusters of T-cell leukaemia caused by HTLV were also found on islands in south-western Japan. Importantly, HTLV was also shown to be present in 10% of healthy individuals living in the environment of diseased people [8, 9]. HTLV was endemic in the Caribbean and may have originated from Africa with the slave trade. The Japanese islands were visited by Portuguese sailors in the sixteenth century, perhaps with crew members from African colonies. In Africa, HTLV was mainly transmitted within certain families, where it seemed to appear generation after generation [10]. Thus epidemiological evidence showed that retroviruses could be pathogenic, contagious through heterosexual transmission, and hide in widely separated clusters for generations, which is helpful in understanding how it was possible for HIV to exist for decades unnoticed in equatorial Africa.

Discovery of the causative agent of AIDS

During the 1960s it was shown that an RNA tumour virus reproduced in a unique way by passing through a DNA phase, using a DNA polymerase. The enzyme was named reverse transcriptase and the entire class of viruses became known as retroviruses. The same observation was published simultaneously and independently by two groups [11, 12], and Temin and Baltimore received the Nobel Prize in Medicine for their discovery in 1975. The discovery was important for the detection of HIV, because rather than looking for the virus directly, reverse transcriptase could be used to trace the virus, which was then demonstrated by electron microscopy or isolation in cell cultures.

A further vital discovery was that of the cytokine interleukin-2 (IL-2) by Gallo’s group in 1976 [13]. IL-2 serves as a growth factor which keeps leukaemic blood cells growing in cell lines, and was key to the discovery of HIV as it allowed the retrovirus to replicate in sufficient quantities to characterize it and transmit it to other cell cultures. The establishment of a cell line [14] was a crucial step for continued practical work.

Initially it was not self-evident that AIDS was one disease entity and that the symptoms which came from almost all organ systems would have one single cause. There were many confusing and distracting circumstances in 1982–1983, not least the life style and sexual practices amongst the homosexual men that were affected. One of the theories raised was that sperm penetrated into blood cells, starting an auto-immune process; another that the immune system collapsed due to overload from many infections.

However, reverse transcriptase activity was demonstrated in specimens from AIDS cases in May 1982 [15]. In February 1983 the electron microscopist of the Pasteur Institute in Paris, Charles Dauguet, demonstrated a new virus in a sample from an AIDS patient. The French group reported on isolation of a T-lymphotropic retrovirus, but as they wrote ‘The role of this virus in the etiology of AIDS remains to be determined’ [16]. Montagnier and co-workers labelled the new retrovirus ‘LAV’, which stands for lymphadenopathy-associated virus. An article was published in Science together with reports from the groups of Gallo and Max Essex, who named their virus HTLV-3, the third human T-lymphotropic virus. It was eventually agreed that the French were first to report the discovery of the virus, and Americans the first to convincingly show that it caused AIDS [15, 17, 18].

Regarding scientific designation and classification, the virus agreed in 1984 to be the cause of AIDS belongs to a different subfamily of retroviruses than the leukaemia viruses HTLV-I and II. The AIDS-virus is a lentivirus (from Latin lentus slow), and the lentivirus group includes the viruses causing the corresponding disease in monkeys, the cat family, horses, cattle and sheep. A nomenclature committee at NIH chaired by Harold Varmus later agreed on the name HIV, which stands for human immunodeficiency virus (analogous to, for example, HBV for hepatitis B virus and HPV for human papilloma virus) [19].

Clinical characteristics of AIDS

Opportunistic infections and tumours are encountered in situations where the immune system is compromised. In the 1960s and 1970s, for example, opportunistic infections were the price of success in children with leukaemia treated with new cytotoxic drugs. The drugs saved their lives but knocked out their already challenged immune system. What was new about AIDS was that immune deficiency and opportunistic infections were occurring as an epidemic, and in strong young people.

The acquired immunodeficiency syndrome is characterized by symptoms and infections caused by the breakdown of the immune system due to HIV infection. HIV can infect many cell types, mainly lymphocytes but also macrophages and microglia in the brain and other neurological cells, resulting in a profound asthenia, dementia and damage to the peripheral nervous system.

Due to the immunodeficiency, patients succumb to various fungi, parasites, bacteria and viruses and are prone to develop certain tumours. As many of these microorganisms and viruses are ubiquitous and generally harmless to immunocompetent individuals, often dwelling in our bodies lifelong without causing damage, they are called opportunistic. Examples are candida, pneumocystis, Cryptococcus, aspergillus, toxoplasma, avian mycobacteria, herpes viruses, varicella and cytomegalo virus. Some of them may have caused a primary infection, especially in childhood, but then dwelling latently in the body. Mycobacterium tuberculosis is the most common killer of HIV infected people in the world, resulting in a fatal combined epidemic of HIV and the tuberculosis bacilli, which often have remained latent in the tissues as a primary infection. The fungus Pneumocystis jiroveci (formerly Pneumocystis carinii) is an important cause of fatal pneumonia. There are geographical differences depending on the local abundance of otherwise harmless microorganisms in the environment, for instance the common opportunistic infection caused by Penicillium marneffei in South-East Asia.

HIV-associated malignancies constitute a major problem. The aggressive type of Kaposi’s sarcoma which is pathognomonic for AIDS in young men was amongst the first signals of the AIDS epidemic in the USA in 1981 and in Africa in 1983 [20, 21]. Kaposi’s sarcoma is caused by a herpes virus known as Kaposi’s sarcoma-associated herpes virus (KSHV). The incidence of the dreaded Kaposi’s sarcoma with its purplish nodules on the skin, particularly obvious in the face, but also in the mouth and inner organs, has diminished where antiretroviral therapy (ARV) is widely available. However, where opportunistic infections have been controlled by ARV and HIV infected people are living longer, AIDS-related malignancies have become the most common cause of death. Epstein–Barr virus (EBV) causes lymphomas in HIV infected individuals and HPV cervical cancer. There is an increased risk of Hodgkin’s disease as well as of rectal and anal carcinomas, but not of colon or mammary cancer.

Chronic incurable diarrhoea with major weight loss and emaciation, sometimes referred to as the enteric type of AIDS, is a very common feature, and gave rise to the popular designation ‘Slim disease’, for instance in Uganda in the early 1980s. The cause is much debated, probably multifactorial. Low-grade fever unrelated to an acute opportunistic infection is another common nonspecific symptom.

Without ARV the fatal course of AIDS takes about 1 year. In the West the fate of people with AIDS was once gruesome, and in poor countries it still is. Previously strong and beautiful young people shrink to gnomes, in poor countries often lying unattended on the floor with fever, coughing due to tuberculosis or pneumonia of other causes, constant diarrhoea and difficulty in eating and drinking due to the pain caused by oral and oesophageal candidiasis. The skin is often affected with large shingle sores (see Fig. 1). People with AIDS are often very weak due to the deep asthenia, sometimes demented, sometimes blind due to cytomegalo-retinitis. They are totally helpless, often abandoned by any remaining family members or chased away to the outskirts of the village by neighbours who are afraid of contracting AIDS. Reportedly, people with AIDS may even be buried alive. Meningitis or septicaemia may shorten the suffering. A visit to hospitals in countries hard hit by HIV presents a monotonous and desperate view; there are AIDS patients in most beds as well as on the floor between.

image

Figure 1.  An HIV infected woman with her child at Nsambya Hospital in Kampala, Uganda, in 1986; fever, asthenia, shingles and oral candidiasis, still not emaciated. (Photo Anders Bjorkman, published with permission).

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Paediatric AIDS is more difficult to recognize, as children often die before developing all the AIDS-defining characteristics, and it is difficult to differentiate between AIDS and malnutrition, other reasons for enteric and respiratory diseases, or tropical fevers. Here, access to HIV testing is crucial.

In industrial countries, a transient primary HIV infection can be recognized, typically 13–14 days after the HIV infection. It is characterized by fever, a sore throat and a skin rash, similar to mononucleosis. HIV antibodies usually appear 3–6 weeks after infection, certainly before 12 weeks. At this time, it is possible to detect antibodies using the regular HIV test – the patient will be ‘HIV positive’. However, the level of virus particles may be high as much as 2 weeks before the antibodies appear, and remains at a high level 3 weeks after the appearance of antibodies. This is the period during which the patient is the most infectious. This is a key observation as well as a trap, and explains why it is so difficult to control the epidemic. The fact is poorly understood by many experts, not to mention authorities. The common HIV test is not yet ‘positive’ and the infected person has not a clue about his or her status. This is also why HIV testing of blood donors using the regular HIV test has limitations – it may not reveal the true condition. Therefore, it is important to look for the virus itself through detection of antigens or viral nucleic acid through PCR.

The virus level in peripheral blood, the viral load, then stabilizes at a level that is specific for each individual. This so-called set point determines the time from infection to development of AIDS, i.e. whether the patient will proceed rapidly to AIDS within months or years, or will be a ‘long term nonprogressor’ for 20 years or even longer. Even during the symptom-free years the gradual destruction of the lymphatic organs continues, the architecture of lymph glands is ruined, for example, and new virus particles are produced, making the HIV-infected person infectious all the time. This is another trap; most people do not know that they are infected, and as they look perfectly healthy, sex partners do not suspect that they might transmit HIV. There is a rapid drop of the number of CD4+ T lymphocytes in peripheral blood, from an average of 1200 cells × mm−3 in healthy individuals to some 500 cells × mm−3 and then, as the destruction of the lymphoid system proceeds, to a defining level of 200 cells × mm−3, when more severe symptoms usually appear. During the phase of AIDS the number of cells continues to decrease (see Fig. 2).

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Figure 2.  Typical course of HIV infection.

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Based on the latest evidence (also used in the 2007 revision of prevalence estimates), UNAIDS/WHO now estimate that the mean time from infection with HIV to AIDS and death, without treatment, is approximately 11 years.

Treatment

At the beginning of the AIDS epidemic, treatment had to be focused on the opportunistic infections. Even this was a problem, as serious infections due to the responsible agents were previously uncommon, and it took time to find optimal treatment.

Antiretroviral treatment started in 1987 with azidothymidine (zidovudine, AZT). Interestingly, AZT is the product of systematic collaboration between private enterprise (the British Wellcome Trust) and publicly financed research (the National Cancer Institute of the US NIH). Both had AZT on their shelves in collections of compounds with possible cytotoxic activities, and the idea occurred that AZT as a nucleoside (thymidine) analogue might inhibit the synthesis of HIV. There was remarkable initial success, but treatment with AZT as monotherapy was unsuccessful due to the development of resistance. It also had a number of undesired effects, such as anaemia, and limitations, such as not affecting virus in already infected cells, and having limited effect in people who had not yet developed AIDS.

In the early 1990s, other nucleoside analogues were developed, as well as nonnucleoside inhibitors of reverse transcriptase. Drugs with other modes of action were introduced, including protease inhibitors and entry inhibitors, and there are now more than 20 different drugs on the market. New developments include integrase inhibitors, CCR5 inhibitors and maturation inhibitors.

The real revolution came when combination treatment with three different drugs was introduced in 1996, thereby reducing the risk of resistance and increasing long-term efficacy. To patients this ‘highly active antiretroviral therapy’ (HAART) meant a mind-boggling change from a death sentence to a new life. However, the treatment itself was very demanding in the first years, with up to 30 tablets to take every day with large quantities of water, and unpleasant side-effects, particularly headache and stomach problems. Treatment has since been improved and simplified, but there are serious side-effects on the liver and haematopoietic organs, as well as metabolic effects resulting in increased levels of lipids and sugar in the blood. The metabolic effects increase the risk of cardiovascular disease and diabetes, as well as causing redistribution of body fat to give the so-called ‘spider body’. The latter is not only cosmetically disturbing but has less obvious consequences such as pain on walking due to disappearance of subcutaneous fat from the sole of the foot.

An interesting new antiviral strategy was outlined at the 2007 International AIDS Society (IAS) conference in Sydney, Australia, involving a ‘triple-R vector’ for HIV gene therapy. The vector attempts to sidestep resistance by expressing a combination of three types of RNA. Stem cells or T cells transduced with this vector are reinfused into patients.

The availability of treatment may have fostered the unfortunate idea that AIDS is not that dangerous anymore, and precautions to avoid exposure are not so important. For this reason, when AIDS infections started increasing again amongst men who have sex with men, gay organizations in San Francisco published ads illustrating the side-effects. Side-effects can be so severe that treatment has to be stopped.

Viral resistance to antiretroviral therapy is an increasing problem, affecting on the order of 10% of patients in southern Europe and 20% in the US. Multi-resistance is increasing, as is pretreatment resistance, i.e. new infections with an already resistant virus. Viral resistance may also vary within the same individual due to the blood and genital area acting as separate compartments; this may have implications for transmitted drug resistance [22].

There are different views on whether treatment should be initiated early, with the aim of hindering the progressive destruction of the immune system. Experience indicates, however, that because of the serious side-effects, poor adherence to treatment, and development of resistance, treatment should only be started when immunity parameters indicate that symptoms are imminent (CD4+ T cells approaching × 200 mm−3). For infants the situation is different; at the 2007 IAS conference in Sydney, interim results from a trial of immediate versus deferred antiretroviral therapy for 6- to 12-week-old infants in South Africa were reported. An independent review panel closed the deferred arm when the risk of death proved 76% lower in immediately treated children.

Postexposure prophylaxis exists, developed primarily for health-care workers accidentally exposed to risk of HIV infection and rape victims. It has even been suggested that people with habitual risk behaviour should be on continuous prophylaxis, and despite the moral and political issues, prevention trials with the drug tenofovir are ongoing in Botswana, Ghana, Peru, Thailand and the US.

To millions of people living with HIV1 in resource-poor settings, treatment is still out of reach. In welfare countries such as Sweden, those who require it have access to treatment, but even in the US, only half of those in need are on continuous treatment, for various reasons. In 2005, only 60 000 of the approximately 22 million people living with HIV in Africa (of whom perhaps 6 million in urgent need) received treatment. In developing countries, not even analgesics may be available, let alone antiretroviral treatment, and HIV-infected people are dying with terrible suffering. Various campaigns have been launched to improve access to treatment. These include the WHO/UNAIDS campaign in 2003, aiming to reach 3 million people by 2005 (the ‘3 by 5’ initiative). The goal was only partly met (1.5 million), but important progress was seen, particularly in Brazil, with its successful national AIDS programme. Even greater ambitions were expressed at the G8 summit at Gleneagles in Scotland in 2005, aiming at ‘universal access’ by 2010. During 2007, the estimated number of people receiving life-lengthening antiretroviral treatment increased to more than 2.5 million people in developing countries.

Cost of treatment is no longer the main obstacle. Drug costs have decreased by 95% in developing countries and more money has been made available in recent years from the Global Fund to fight AIDS, Tuberculosis and Malaria, the World Bank, and bilateral (country-to-country) development agencies, in particular the US President’s Emergency Plan for AIDS Relief (PEPFAR). The main problems lie in lack of political will and lack of healthcare infrastructure, including the drain of trained health-care workers from developing countries to the West. Another major problem is stigmatization, women in particular not daring to be tested and receive treatment for fear of being thrown out by their families, beaten, or even killed. However, the process of making treatment accessible to more people in resource-poor countries is under way.

Efforts to develop a vaccine

In 1984, the US Secretary of Health promised that a vaccine would be available within 2 years. At a WHO vaccine meeting in 1986, it was more conservatively concluded that a vaccine for general use would not be available until the mid-nineties –‘if at all possible’. Now more than 20 years later, there is still no vaccine in sight; the forecast has been moved to 2015, and the caveat remains valid. Why is it so difficult? The answer lies in three key characteristics of HIV which differentiate it from common acute infections: the persistency of the infection, an extreme ability to mutate and thus escape immunity, and destruction of the immune system.

A conventional way of making vaccines, including those against measles, rubella and mumps, is to use live, attenuated infectious agents. One dares not use attenuated HIV as a vaccine, however, due to its ability to integrate with the DNA in our own chromosomes and to mutate easily. It cannot be guaranteed that a weakened virus will not mutate back to a virulent form or pick up pathogenic properties from wild virus, and unexpected side-effects in a vaccinated population might only appear after decades, with catastrophic consequences. Another conventional method is to use complete infectious agents or their toxins as a vaccine after making them harmless through heating or chemical treatment. The trend is to use vaccines composed only of the purified components required to create immunity, i.e. subunit vaccines. An example from HIV research is gp 120, a purified glycoprotein from the virus envelope.

The aim of such vaccines is to produce neutralizing humoral antibodies. The problem is that in contrast to other infections, such as measles, HIV infection does not provide any lasting protective immunity in spite of the usual range of immune responses. Circulating antibodies appear within weeks, and are the basis for the usual HIV test, but the infection continues its course to AIDS, in the meantime destroying the cells responsible for the development of immunity. Demonstration of antibodies and cellular immunity to a new vaccine is easy, and can be carried out in small laboratory animals such as mice, but to get an indication of whether they are protective against infection, nonhuman primates are needed, which is expensive and ethically loaded. Interestingly, chimpanzees can be infected with HIV but do not develop AIDS, and the most useful model has in fact been provided by macaque monkeys and HIV-2. Simian immunodeficiency virus (SIV), which is identical to HIV 2, does not cause AIDS in African monkeys, but if Asian macaques are infected, they do develop AIDS. Unfortunately, vaccine candidates that have been built on promising results in monkeys have not proven effective in trials in humans.

The first decade of research into vaccines was focused on humoral immunity, i.e. blood-borne neutralizing antibodies, but it was found that these did not provide sufficient protection. The antibodies produced had very little neutralizing effect. This tendency to follow current ‘fashions’, not least due to association between such trends and the possibility of obtaining research grants, may have delayed HIV vaccine development for several years. The second generation of vaccines builds on the importance of cellular immunity and the stimulation of T cells. Examples are live virus recombinants, in which relevant structures from HIV are incorporated into a vector virus that is harmless to humans. One of the best-known examples is ALVAC-HIV, a nonreproducible recombinant of HIV and live canarypox virus. It is combined with gp 120 which mediates neutralizing antibodies. ALVAC is being tested in a large phase-III study in Thailand (ClinicalTrials.gov Identifier: NCT00223080), and results are expected in 2009–2010. In September 2007 it was announced that a phase 3 efficacy trial with approximately 3000 participants in North and South America, the Caribbean and Australia with an adenovirus-based vaccine from Merck had been discontinued because of failure to demonstrate protection. Another trial with the same experimental vaccine in South Africa was stopped when it turned out that the vaccine was associated with a higher, rather than lower, risk of contracting HIV compared with placebo (19 persons contracted HIV compared with 11 of those receiving placebo).

Clinical testing of vaccines is laborious and time-consuming, and has specific problems, such as benefit-risk considerations when the subjects are healthy people rather than people with a disease, who might benefit from the trial drug. Large clinical phase III trials take several years to complete, by which time the scientific concept they are testing is usually out of date. A problem specifically related to HIV vaccine trials is that people with antibodies risk discrimination for being ‘HIV positive’ though not infected. Another difficulty is uncertainty about the need for different vaccines depending on subtypes of virus – in fact it seems that the present subtype classification does not correspond with differences in immune response, and a whole new classification may be necessary. Further, there has been a wide-spread suspicion of HIV trials in poor countries, particularly in Africa, due to two notions: that rich countries use Africans as guinea pigs, and that Western countries wish to spread HIV in Africa through childhood vaccinations in order to control population growth. At a meeting arranged by WHO/UNAIDS in Geneva in 2003, it was emphasized that clinical studies must imply a clear and direct advantage to the population where the study is being performed.

Two entirely different approaches to HIV vaccination have been discussed, one to prevent infection, the other to prevent disease. Many scientists are now pushing for so-called therapeutic vaccines that can be used instead of or in combination with antiretroviral drugs. The effect of such a vaccine can be registered rapidly by following health status, virus reproduction and blood cell counts.

A major practical obstacle to developing an HIV vaccine is the lack of a correlate (surrogate marker) whereby protective effect can be measured; no animal or laboratory tests reveal whether a product will protect humans, and direct testing in humans is necessary. Another key issue is scientific uncertainty – it is still unclear which biological factors are crucial to prevent HIV infection. Other problems include patent questions, high development costs and liability risks, all of which make pharmaceutical companies hesitant to invest in vaccine research. A final issue is how to gain acceptance for vaccination if and when it becomes available. It cannot be taken for granted that people will line up to be vaccinated against AIDS, that shameful disease. If people believed they were at risk, there would be no epidemic. A conceivable scenario is mandatory general vaccination in the worst-affected countries, similar to that once imposed against smallpox.

Preventive measures

In the absence of a cure and with limited access to anti-retroviral treatment, especially in the worst-affected regions, there are a number of measures which can be helpful in reducing further spread of the epidemic.

The first is dissemination of knowledge on how HIV is spread and not spread. In 2005, more than 50% of people between 15 and 24 years were unaware how HIV is transmitted [23]. Surveys have shown that in Bolivia, for example, 74% of young women did not know that AIDS existed, or had serious misconceptions on the subject, and in large parts of Asia, the majority of young women did not even have elementary knowledge on how children are created. Knowledge does not automatically lead to appropriate behaviour, however, as exemplified by the recent increase in transmission of HIV amongst homosexuals in the West, and the fact that doctors, nurses and AIDS counsellors are infected with HIV and die of AIDS in Africa to the same extent as the rest of the population. There is also a dilemma in whether information campaigns should be aimed at the whole population or at individuals with special risk behaviour. Furthermore, information does not work for those with no possibility to choose, such as married women, prostitutes, women in dependency situations, and all those who cannot say no to unwanted sex. Nor does information help those under the influence of alcohol or other drugs. Sexual education is also resisted in countries with a Victorian and fundamentalist attitude, such as USA, Russia, and Muslim countries, as it is assumed to lead to promiscuity amongst youths.

The transmission of HIV from mother to child can be reduced significantly through use of antiretroviral treatment during pregnancy and delivery, and by their infants after birth. Sadly, in 2005, less than 9% of pregnant women with HIV in low- and middle-income countries received antiretroviral prophylaxis to prevent mother to child transmission.

Refraining from breast-feeding also reduces the risk, but the current consensus is that women with HIV should only avoid breastfeeding if there is access to a continuous and safe supply of breast milk substitute, as otherwise the lives saved by prevention of AIDS will come at the price of even more lives lost from diarrhoea, respiratory diseases and malnutrition. Breastfeeding without supplements reduces the risk of HIV infection compared with mixed feeding.

Another preventive measure is treatment of other sexually transmitted infections. There is a strong correlation between contagiousness for HIV and the presence of such infections, both for epidemiological reasons, with the same risk factors and core groups spreading infection, and biological reasons, inflammation leading to concentration of CD4+ and other leucocytes which are receptive to HIV, and direct sores in the epithelium increasing the risk of infection.

Condom use is the least expensive and most cost-effective method for preventing HIV transmission. However, condom promotion is resisted by fundamentalist groups, such as the Vatican, and the religious right in the US, and may be a difficult subject in marriage.

Male circumcision reduces the risk of HIV transmission by approximately 60%, apparently due to the large number of Langerhans cells in the preputium. In March 2007, WHO and UNAIDS announced recommendations that male circumcision should be considered an important intervention, used as part of a comprehensive prevention package [24].

HIV testing with counselling is aimed especially at blood donors and pregnant women. Testing on a broad scale and partner notification has often been seen as encroaching on personal integrity, but after initial suspicion is becoming accepted and implemented in more and more countries. Access to antiretroviral treatment increases acceptance for testing, as it provides an incentive to the person being tested, and if the person is HIV-positive, the step to notifying a partner who can also be offered treatment is not so steep. However, the majority of the people infected with HIV in the world today still do not know that they are infected.

Microbicides

Since the beginning of the 1990s there have been many attempts to develop topical preparations of microbicides for vaginal use. The idea is to offer an alternative to condoms to prevent HIV infection, which can be used by women without the need to negotiate with a male partner. Initially, a well-known spermicidal compound, nonoxynol-9, was tested but trials had to be stopped as it caused abrasions and inflammation of the vaginal wall after frequent use and therefore might promote HIV infection. Other compounds have also turned out to be irritant or ineffective. Antiretroviral compounds are also being tested, but in optimizing local efficacy it has been difficult to limit systemic absorption and the consequent risk of toxic side effects or development of viral resistance. Perhaps the most sobering basic research presented in the 2007 IAS conference in Sydney came in a report identifying and characterizing resistant virus selected by an anti-HIV microbicide. Another issue is whether a spermicidal effect is wanted or not when used within marriage. Ideally, the substance should not only be virucidal but also kill other germs causing sexually transmitted infections.

Epidemiology

  1. Top of page
  2. Abstract
  3. Introduction
  4. Biomedical overview
  5. Epidemiology
  6. Social and political aspects
  7. Denial, disinformation and misconceptions
  8. Discussion
  9. Conflict of interest statement
  10. References

Where did HIV come from?

The natural hosts of the lentiviruses related to human beings are nonhuman primates. The chimpanzee virus is labelled SIVcpx and is closely related to HIV-1 which is causing the human pandemic. SIVcpx has mainly been found in chimpanzees living in the wild in Western Equatorial Africa (Gabon and Cameroon), and does not cause disease in chimpanzees. A monkey virus (SIVsm) is closely related to HIV-2, which is mainly found in west Africa, is less transmissible than HIV-1, and only causes AIDS in humans after a very long time. Through sophisticated genetic analysis it is possible to trace the origin of HIV-1 back to approximately 1930, when a common ancestor was transferred from chimpanzee to man [25]. It is likely that the species barrier was crossed more than once, and seems to have occurred more often with HIV-2 than HIV-1 [26].

There are 3 major groups of HIV-1 as well as subtypes, known as clades. There does not seem to be any difference in virulence or other biologic characteristics between the clades. Due to its dynamic nature, HIV-1 is continuing to evolve, developing recombination subtypes. Subtypes can be used as epidemiological markers to identify transmission routes, e.g. from Thailand or from Russia. The likely area of origin of HIV-1 is supported by the fact that Gabon and Cameroon have a uniquely broad spectrum of HIV viruses, including all the major groups as well as the subtypes. Thus it is likely that the transfer of the original virus occurred in this part of Africa, through hunting and butchering, and may indeed still be occurring. It is also possible that the chimpanzees themselves once acquired the SIVcpx virus by hunting and eating lower monkeys.

AIDS thus resembles a zoonosis, in common with other major scourges such as plague, influenza and rabies, but is not a true zoonosis in that it does not depend on a continuing interplay between man and animal. Considering that chimpanzees are threatened with extinction, the well-consolidated move to humans has proved to be an extremely successful survival strategy for HIV.

Earliest reports of AIDS

Retrospective research indicates that isolated AIDS cases occurred as early as the 1950s. One of the earliest described was an English sailor from Manchester who died in 1959 at the age of 26. He suffered from chronic gingivitis, extreme loss of weight, persistent cough, shortness of breath, and oro-nasal and anal ulcers which grew progressively worse [27]. Autopsy showed pneumonia caused by Pneumocystis carinii as well as cytomegalovirus in tissues and herpes virus around the anus. In the 1990s attempts were made to amplify HIV-1 sequences by PCR from saved specimens, though the results have been questioned [28]. Another well-known case is the ‘Norwegian sailor’ who died in 1976 with pneumonia, dementia and severe neurological symptoms, and whose wife died 8 months earlier with a similar clinical picture. A child born to the couple in 1967 acquired septicaemia caused by candida and died in 1976 in generalized chicken pox. Stored blood samples from all three were later shown to be HIV-positive. Thus the infection probably occurred before 1967, considering the likelihood of vertical transmission to the child. A further well-documented example concerns a Danish surgeon, Grethe Rask, who worked for many years in a remote village in what was then northern Zaire and who died with a clinical picture characteristic of AIDS in Denmark in 1977. Autopsy revealed massive Pneumocystis pneumonia.

Mirku Grmek refers in the 1989 book History of AIDS to the malignant type of Kaposi’s sarcoma in combination with meningitis and pneumonia which occurred during the early 1960s in seasonal workers moving between Central and South Africa. This combination is strongly suggestive of AIDS. Stored blood specimens show that HIV existed in Congo in 1959 but was rare, and samples from 1976 also indicated a low-frequency distribution of HIV in this part of Central Africa. HIV was in fact successfully isolated from a stored sample taken from a man in Leopoldville (Kinshasa) in 1959. The virus was analysed using modern molecular biological methods in 1998 and found to be related to now-common subtypes of HIV-1 [28]. The genetic composition corresponds well to the proposed continuous development of HIV-1 from 1930 until now.

AIDS in Africa

From its proposed place of origin in Western Equatorial Africa, it is believed that HIV transmission radiated to the Ivory Coast and eastwards through Congo to Rwanda [29, 30] and East Africa along rivers and trading routes and later to Southern Africa (see Figs 3 and 4). From 1983, AIDS increased at a rapid rate on both sides of the border between Uganda and Tanzania on the western shore of Lake Victoria. Considering the average lapse of 11 years between infection and the manifestation of AIDS, it can be assumed that widespread dissemination occurred in the 1970s in this part of East Africa. This corresponds to a time when this region was at the centre of war operations (the ousting of Idi Amin) as well as intense trading and smuggling.

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Figure 3.  Sketch of probable transmission of HIV in Africa, from Western Equatorial Africa over the Congo Basin to East Africa and further north and south.

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Figure 4.  Transmission of HIV over the globe in 1985, 1995 and in 2005. Reproduced with kind permission of UNAIDS (2006).

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Levels in the Congo never reached the extremely high levels of East and Southern Africa. There were epidemics in some West African countries such as the Ivory Coast, but in Nigeria, HIV did not spread as rapidly as expected. Prevalence also remained low in Arab North African countries. Angola was shielded from HIV for many years by civil war. Similarly, under apartheid, South Africa was isolated from the wide spread of HIV in neighbouring countries such as Zambia and Zimbabwe, although it is likely that there was a higher HIV frequency amongst the migrating black workforce in the mining industry. When the borders opened in 1994 after the fall of apartheid, people poured back from exile, many carrying with them HIV infection, leading to a major but silent heterosexual spread.

It was well into the 1980s before the AIDS epidemic in Africa became known to the world, and experts found it hard to accept that HIV could spread heterosexually on a wide scale, as in Africa. Even when it became obvious that there was a widespread epidemic of AIDS in Africa, many western researchers considered it another type of AIDS, ‘African AIDS’.

Africa south of the Sahara now contains more than two-thirds of the people living with HIV worldwide, 22.5 of 33.2 million. The epidemic in East Africa seems to have peaked at the end of the 1990s and to have stabilized at a lower level with a prevalence around 7% (still very high in a global comparison). In the adult population 15–49 years of age, 26% are infected in Swaziland, 25% in Botswana, 18% in Zimbabwe, 16% in South Africa, 16% in Zambia and 16% in Mozambique. The proportion of pregnant women that are infected with HIV is even higher, 32% in Botswana and 29% in South Africa (see Fig. 5).

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Figure 5.  HIV prevalence by age group amongst ante-natal clinic attendees in South Africa from 2000 to 2005. Reproduced with kind permission of UNAIDS (2006).

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AIDS in the West

In November 1980, Dr Michael Gottlieb at the University of California, Los Angeles (UCLA) saw a patient with severe candida infection in the mouth, which was unexpected in an otherwise seemingly healthy 30-year-old man. A few days later the patient complained of coughing and breathing difficulties, and turned out to have pneumonia caused by Pneumocystis, usually only seen in patients with severe immune deficiency. Blood tests showed deficiency in T-helper cells. During the next few months, Dr Gottlieb encountered Pneumocystis pneumonia in four further patients, who had in common with the first that they were all previously healthy young homosexual men. These findings were reported in a weekly publication by the CDC on 5 June 1981 [31]. A further report was issued a month later [32], describing 26 men with Kaposi’s sarcoma, several of them also suffering from Pneumocystis pneumonia, toxoplasmosis, and serious infections due to fungi and herpes virus. These two reports have become defining events in the history of AIDS, leading to hectic activity by the federal CDC and shaking the gay community.

Epidemics need a critical mass to start, an accumulation of people who are susceptible to the contagious agent and a sufficient dose for the infection to catch. In connection with the sexual liberation of homosexual men in the 1970s, a subculture arose, particularly in San Francisco, Los Angeles and New York, of unrestrained sexual expression linked to bathhouses and clubs (described in more detail in Randy Shilts’ book from 1987 And the band played on). This bathhouse culture offered an ideal environment for spreading HIV: many partners and high-risk sex practices. Without these opportunities, it would be difficult to understand how there could be an epidemic in the USA, as HIV is not easily transmitted. Via homosexual networks, HIV was disseminated across the world to local circles with a similar life style, but transmission to other groups of society does not seem to have been great. The advantages of AIDS first becoming known in California are that medical and scientific resources were available to investigate the epidemic, and that AIDS became rapidly known on a global scale. The disadvantage is that AIDS became associated with homosexual men and a ‘decadent western lifestyle’.

There have been many speculations about how HIV was transmitted out of Africa to explode amongst the homosexual people and drug users in North America in the early 1980s. One theory is that people from French-speaking countries in the Caribbean picked up HIV when they were brought in to fill the gap of key officials and specialists after the Belgians left Congo in the 1960s. When the Carribbeans returned home they may have transmitted HIV to North American vacationing gay people. Others maintain that it was the other way around, Haitians were infected by the North Americans. Americans could just as well have been infected directly in Africa. This is a morass of speculations with racist overtones, and there has been a lack of scientifically sound explanations for how HIV started its global travel. However, new data propose a geographic sequence and time line for the emergence of HIV-1 subtype B out of Africa by analyzing archival samples from the earliest known Haitian AIDS patients [33].

In the Western world, transmission of HIV to the general population did not occur but continued in groups with risk behaviour. Reduced risk behaviour led to a decline amongst gay people for some time, but there were explosive outbreaks amongst injecting drug users in new areas such as Spain, Portugal and Italy. The situation in Australia and New Zealand developed along the same lines as in Western Europe. Gradually, politicians, media and public lost interest as there seemed to be no danger of a generalized epidemic in this part of the world.

The number of people living with HIV in western and central Europe and North America reached approximately 2.1 million in 2007. The 32 000 people that died of AIDS and 78 000 new infections fade into insignificance in comparison with the numbers from other regions, but are still alarming after more than 20 years of intensive information and 10 years of highly active anti-retroviral therapy, and both new infections and deaths are on the increase. There is a marked difference in HIV prevalence even in the West between continents and subregions. For instance, the US has twice the estimated adult HIV prevalence compared to Canada, 0.6% compared to 0.3% (2005 figures). Spain and the US are at the same level, whilst the level in the UK and Sweden is only a third of this, i.e. 0.2%. These figures are still very low in an international comparison. An increasing proportion of newly acquired infections are due to heterosexual transmission, although men who have sex with men and injecting drug users still account for the majority of cases. Bisexuality amongst men appears to be a more important reason for infection of women than previously realized, the man keeping his bisexuality secret from his wife or partner.

In western Europe, there is an increase in HIV infections linked to immigration and migration of people from countries with high HIV prevalence, especially sub-Saharan Africa. These account for 75% of heterosexually acquired new infections. However, domestic transmission continues to increase amongst men who have sex with men, and transmission through injected drug use also still occurs. There also seems to be a tendency amongst young infected people to mistakenly think that curative treatment now is available.

AIDS in other parts of the world

In Asia, HIV only started to spread towards the end of the 1980s, predominantly amongst injecting drug users in areas around the opium-producing Golden Triangle. It was then transmitted to the heterosexual population through female sex workers, which was particularly obvious in Thailand, with an alarming spread to military recruits. This prompted resolute and successful measures by the Thai government, especially the famous ‘100% condom use’. HIV continued to gradually spread over India and China, mainly through injecting drug users and heterosexual contacts through sex workers and truck drivers.

Transmission in Asia is still primarily linked to injecting drug use. Heterosexual transmission comes as a second wave when the male drug user infects his female partner, who is often forced into prostitution to pay for drugs. Prostitution contributes to continued heterosexual transmission. This pattern has been seen in Thailand, India, Vietnam, China and the former Soviet Union, and HIV is spreading across the Eurasian continent.

AIDS in the former Soviet Union and neighbouring communist countries was considered a minor problem associated with the capitalist lifestyle, and widespread testing initially showed very few positive findings. However the opened borders and transition to a market economy involved the fastest growth of HIV infection in the world. Russia and the Ukraine account for the majority of cases, with a prevalence of 1.1% of the adult population in Russia and 1.5% in the Ukraine. The difference between the Ukraine and its next-door neighbour Poland is startling, with a 15 times higher prevalence in the Ukraine.

Specific to the HIV epidemic in eastern Europe is that people subject to HIV infection through injected drug use and high-risk sexual behaviour are very young. This results in a highly dynamic epidemic, with a much greater potential to spill over into the general population than the concentrated outbreaks amongst marginalized drug users typically seen in the West. Russia also has a very high prevalence of other sexually transmitted infections, which increases the risk of HIV transmission. In addition, Russia also has the highest opium addiction in the world, with about 1 million people affected, partly as a result of the ill-fated war in Afghanistan. One of the culprits for the spread of HIV is the habit of cooking so-called ‘compote’ from poppy seed, and clearing the resulting murky liquid by adding human blood before injecting it.

In China there are an estimated 650 000 people living with HIV, which is less than in Russia despite 10 times the population. China is also implementing resolute measures in accordance with UN best practice to control the epidemic.

India has an estimated 2.5 million people living with HIV. Although this is one of the highest numbers in the world, it represents less than 0.4% of the adult population, and as in Russia and China, most infected people live in limited geographical areas. Higher concentrations are reported from the industrialized areas and from the north-eastern areas bordering on the Golden Triangle, where injecting drug use is the main risk factor. Most infections are transmitted through heterosexual intercourse and the proportion of infected that are women is increasing (as everywhere else) – in 2005 it was approximately 40%.

Thailand has a higher prevalence than India and China, i.e. 1.4%. Of new HIV cases, 43% occurred among women, the majority of whom are housewives who propably contracted HIV from husbands who have had casual sex or injected drugs.

The Caribbean developed an AIDS epidemic depicted to be as bad as that in sub-Saharan Africa, with Haiti being worst affected. However, the HIV incidence started to fall as early as around 1990. The majority of people living with HIV can be found in Haiti and the Dominican Republic, with an estimated adult prevalence of 2.2% and 1.1% respectively. Cuba has the lowest prevalence in the Caribbean (and lower than the US).

It was initially feared that the AIDS epidemic would be severe in Latin American countries, with the focus on Brazil. However, Brazil has attracted attention as a model of successful measures to control HIV. It has impressed the world with an open attitude, and applied the entire arsenal of preventive measures: sex education in schools, condom use, harm reduction, HIV testing and prevention of mother-to-child transmission. The adult prevalence level has thus been kept to a steady 0.5%, which is lower than in the wealthy USA. Brazil also provided anti-retroviral therapy free of charge at an early stage.

The current epidemiological situation

Estimates of HIV prevalence were previously often based on so-called sentinel surveillance in pregnant women at antenatal clinics, as this testing is systematic and a standardized method was already developed by the WHO Global Programme on AIDS in the late 1980s. However, recent population-based surveys have consistently given lower figures than antenatal testing (approximately 80% as high), and many estimates were revised downwards in the UNAIDS 2007 Epidemic Update. An extreme example is India, where the previous estimate of 5.7 million people living with HIV was recently revised to 2.5 million after an expensive survey comprising the remarkable number of 120 000 households. Estimates are usually given with a range defining the boundaries within which the actual numbers lie, ‘based on best available information’.

Already, approximately 25 million people have died of AIDS and a further 33 million have been infected with HIV (see Table 1). Almost half of the people living with HIV are women. In sub-Saharan Africa the figure is approximately 60%, and in teenagers, the prevalence might be up to 25 times higher in girls than in boys [34] (see Fig. 6). In 2007, approximately 2.5 million people were newly infected and 2.1 million died.

Table 1.   Summary of epidemiological situation in December 2007, by region
RegionLiving with HIVNewly infected with HIV in 2007Died of AIDS in 2007
  1. aOf whom 360 000 (350 000–540 000) children <15 years.

  2. Ranges define the boundaries within which the actual numbers lie, based on best available information.

  3. Source: UNAIDS. AIDS epidemic update 2007.

North America1.3 million (480 000–1.9 million)46 000 (38 000–68 000)21 000 (18 000–31 000)
Caribbean230 000 (210 000–270 000)17 000 (15 000–23 000)11 000 (9800–18 000)
Latin America1.6 million (1.4–1.9 million)100 000 (47 000–220 000)58 000 (49 000–91 000)
Western and Central Europe760 000 (600 000–1.1 million)31 000 (19 000–86 000)12 000 (<15 000)
Middle East and North Africa380 000 (270 000–500 000)35 000 (16 000–65 000)25 000 (20 000–34 000)
Sub-Saharan Africa22.5 million (20.9–24.3 million)1.7 million (1.4–2.4 million)1.6 million (1.5–2.0 million)
Eastern Europe and central Asia1.6 million (1.2–2.1 million)150 000 (70 000–290 000)55 000 (42 000–88 000)
East Asia800 000 (620 000–960 000)92 000 (21 000–220 000)32 000 (28 000–49 000)
South and south-east Asia4.0 million (3.3–5.1 million)340 000 (180 000–740 000)270 000 (230 000–380 000)
Oceania75 000 (53 000–120 000)14 000 (11 000–26 000)1200 (<500–2700)
Total32.2 million (30.6–36.1 million)2.5 million (1.8–4.1 million)2.1 million (1.9–2.4 million)a
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Figure 6.  Estimated prevalence of HIV by sex and age in South Africa, 2006. Source ref. 34.

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HIV prevalences are generally low in Muslim countries, for example countries in North Africa, the Middle East, Indonesia, and parts of India. This may be due to factors such as circumcision in men and stricter social control of female sexuality.

A major obstacle to prevention of further transmission of HIV is that many people are unaware that they are infected. These may account for many if not most of the new infections. In the USA, 25% of those living with HIV are unaware of it; in Europe, the proportion is as high as one-third, and the rate of diagnosed new infections has doubled since 1998.

There are many speculations as to why HIV infections are more common in Africa than elsewhere and why there are such big differences in HIV prevalence even between African countries. Studies have shown that the lack of male circumcision and the Herpes virus type 2 (HSV-2) prevalence are the most powerful factors associated with differences in HIV prevalence [35–37]. Concurrent sexual partnerships are another factor explaining the high HIV prevalence in some African countries [38].

A case history

What is the reason for the big difference between the HIV epidemics of Uganda and South Africa? One major difference is in timing. When HIV was silently spreading in Uganda during the 1970s and early 1980s, AIDS had not yet been described and the infectious agent was unknown. Apparently, president Museveni of Uganda first learnt several years later from Fidel Castro that Ugandan soldiers sent to Cuba for training were HIV infected. Once this threat to the army became clear Museveni started a frank campaign to request ‘zero grazing’ for men, an expression easily understood by pastoral people (tethered cattle graze in a circle). The president explained to the people how HIV was and was not spread and it became possible to talk openly about AIDS. The very high incidence of HIV infection in pregnant women decreased over time from around 30% to 6%. Museveni achieved international accolade for his success.

In South Africa, HIV distribution only exploded in the mid-1990s, when the African HIV epidemic was well known. However, neither President Mandela nor President Mbeki ordered countermeasures, and silence ruled until the year 2000. Then, just before the International AIDS Conference in Durban, Mbeki publicly proclaimed that AIDS hardly existed in the country and that it was not caused by an infection but by poverty, a colonial heritage. The minister of health has been notorious in denying HIV and in resisting antiretroviral treatment and prevention of mother-to-child transmission. Only recently and reluctantly when South Africa already had the highest HIV/AIDS load in the world was the government forced to take rational action, pressured by the vital force of South African nongovernmental organizations and global opinion.

Social and political aspects

  1. Top of page
  2. Abstract
  3. Introduction
  4. Biomedical overview
  5. Epidemiology
  6. Social and political aspects
  7. Denial, disinformation and misconceptions
  8. Discussion
  9. Conflict of interest statement
  10. References

Global response to the HIV pandemic

In the West the initial response to the appearance of AIDS was by public health authorities, at the local and national level. Very soon gay volunteer organizations started to react; after a first defensive denial attitude suspecting just another attack on gay liberation, they organized in self-help groups and activist initiatives to raise awareness amongst authorities and politicians. In the USA, the Federal CDC was engaged from the very beginning, in the early 1980s.

In Africa there was first a denial phase by governments as reports that AIDS was occurring in a country were seen as racist accusations and a threat to tourism. The World Health Organisation (WHO) gradually managed to convince most governments about the seriousness of the situation. However, there was and still is a dilemma regarding how to balance allocation of interest and resources between HIV/AIDS and other major health problems such as tuberculosis, malaria and other tropical diseases. As late as in 1984 the Director-General of the WHO himself publicly claimed that AIDS was a ‘San Francisco hype’ of no concern to Africa and should not be allowed to take the focus away from malaria and other major diseases. However, by providing information about the rapid spread of AIDS in Central and East Africa, we managed to convince him about the need to direct interest towards AIDS as a threat to developing countries. In 1985, WHO arranged the first meeting on AIDS in Africa. At that meeting in Bangui, in the Central African Republic, we identified the clinical criteria to diagnose AIDS. This was of key importance in order to estimate the true size of the epidemic, particularly with reference to the political sensitivity and denial amongst the African countries. Large-scale HIV testing was not a realistic alternative at that time.

In 1986, WHO started a Special Program on AIDS, later named the Global Program on AIDS (GPA) and developed a global strategy on AIDS which was adopted by the UN General Assembly in 1987. For the highest UN body to debate a single disease was unique, and indicates the particular political importance of AIDS. The resources and tasks of the GPA grew rapidly, financed by extra-budgetary sources from a handful of donor countries, another remarkable feature. The GPA gained an unusually independent position under the leadership of the charismatic Jonathan Mann, which eventually resulted in a clash with the new WHO Director General, Hiroshi Nakajima and the dramatic decline of Mann. There was also a destructive competition between WHO and the other specialized UN agencies, for instance the large Development Program (UNDP), Family Program (UNFPA) and UNICEF.

Initially, some agencies did not want to be associated with AIDS with its burden of homosexuality, prostitution and drug use. For instance, UNFPA already had enough difficulties in marketing population control and sexual education in the world in the face of fundamentalist beliefs and traditions, such as the policies of the Vatican and Muslim faith as well as of conservative governments. Condoms for contraception came into even greater disrepute due to the association with prostitution and homosexuality. UNICEF also felt uncomfortable in having to fight prejudices against AIDS as long as mother-to-child transmission of HIV, paediatric AIDS and heterosexual transmission to young girls were not recognized as major problems in poor countries.

When the financial resources from donor countries increased, competition for funding arose amongst the UN agencies, leading to rivalry and duplication of activities. Eventually, donor countries lost patience and in 1996 created a Joint Program on HIV/AIDS (UNAIDS), composed of the ten UN agencies with activities against AIDS (2). The GPA ceased to exist in 1995. UNAIDS is not another UN agency but a joint co-ordinating secretariat, located in Geneva, with administrative support from WHO. It is funded by donor countries and headed by an Executive Director, Peter Piot, appointed by the UN Secretary-General. UNAIDS has a board composed of donor and recipient countries plus representatives of international networks of people living with HIV/AIDS and other civil society organizations.

The GPA initiated AIDS Programmes in developing countries under the ministries of health, often administered by a national AIDS committee. The activities of national AIDS programs were based on the Global AIDS Strategy and evidence-based ‘best practice’. The GPA provided grants as seed-money to poor countries, which for the rest rely on funding from rich countries. Seldom have developing countries used resources from their own national budgets to fight AIDS, which reflects a lack of recognition of AIDS as a national priority, or rather a lack of care by the rulers for the wellbeing of their own subjects. Many political rulers consider the population as a resource, not as a responsibility. The people are there for them, not the other way around.

UNAIDS is not a funding agency. Instead poor countries receive support from UN agencies or directly, bilaterally, from industrialized countries, from the EU or nowadays also from private donors such as the Bill and Melinda Gates Foundation. European countries pay in three different ways, which is not always realized: to UN agencies, to the EU and bilaterally.

A major milestone in the global response to AIDS was the UN General Assembly Special Session on AIDS in 2001 (UNGASS 2001) when all of the then 189 countries of the world solemnly committed themselves to reach a number of targets. Examples of targets for 2010 were to reduce HIV prevalence amongst people aged 15–24 by 25% globally, to ensure that at least 95% of people aged 15–24 have access to information ‘required to reduce their vulnerability to HIV infection’ and to reduce the proportion of infants infected with HIV by 50%, especially by increasing access to anti-retroviral therapy. These targets are a further specification of the general UN Millennium Goal to halt and begin to reverse the spread of HIV/AIDS by 2015.

In 2007, a high level meeting of the General Assembly reviewed the progress of UNGASS 2001 after 5 years. There was some progress with regard to changes in the political environment, setting national targets, estimating resource needs, expanding treatment and intensifying prevention, but also depressing failures. In particular, no more than 8% of HIV-positive children estimated to be in need of antiretroviral drugs in low- and middle-income countries have access to them. The proportion of pregnant women receiving service to prevent mother-to-child transmission of HIV increased from 9% in 2005 to only 11% in 2006. This reveals a shocking lack of political will in low- and middle-income countries. It remains to be seen if governments will live up to their declared commitments in the coming years.

Since 2001 a new funding mechanism exists through the Global Fund for AIDS, Tuberculosis and Malaria (Global Fund). The Global Fund is not a UN body, which is important to prevent UN member countries requesting what they consider to be ‘their fair share’ of the money, regardless of how the funds are used or whether they disappear through corruption or mismanagement. The Global Fund was initiated by the former UN Secretary-General Kofi Annan and is financed by public and private donors: governments, business sector and private philanthropists. As of September 2007, the Global Fund has disbursed US$4.3 billion, which makes it a major actor. In some countries it is the only major donor, e.g. in the Ukraine and many other countries in Eastern Europe and Central Asia. This is a problem as countries then are dependent on one financing source, which in turn is dependent on further annual pledges by the international community. Organizations of people living with HIV are concerned that the supply of antiretroviral drugs will stop if the Global Fund does not succeed in getting new pledges.

The Global Fund works in a similar way to research granting funds: governments and civil society organizations have to apply for funding in applications describing purpose, measurable outcomes, validity and financial and reporting plans. If the plans are not adhered to or money is mismanaged the Fund withdraws its support, which has happened, for instance, in Uganda, South Africa and the Ukraine. The first application by the Russian government was declined by the Fund, which instead approved an application from a Russian nongovernmental organization, a tap on the nose to the Russian authorities who are trying to rein in the freedom of civil society organizations.

UNAIDS released a report in 2007 on the estimated financial resources required for the AIDS response [39]. Despite marked increases in funding for the HIV response during this decade (it reached US $10 billion in 2007), the gap between resources available and the amount needed will widen if current trends continue. Two scenarios are presented for rectifying the situation. The first envisages an urgent expansion of coverage in all countries, achieving universal access by 2010 in accordance with globally agreed goals. The second scenario assumes different rates of scaleup for each country, with essentially all countries reaching universal access by 2015. The projected costs are considerable, rising to US $42 billion by 2010 and US $54 billion by 2015 for the first scenario, and US $28 billion by 2010 and US $50 billion by 2015 for the second. However, a major part of the cost includes general health system strengthening, and if the costs are not faced now, they will be even higher in the future.

A considerable share of the AIDS assistance is paid by the G8 countries, by the USA in particular, and HIV/AIDS is on the agenda of the annual G8 summits. Unfortunately, the commitments and pledges made at these meetings are optional; the political rhetoric has to be considered as nonbinding and is not intended to be fully honoured.

A comparatively new trend in the global response to AIDS is corporate contributions given as part of the social responsibility of commercial companies. These include the Global Business Coalition and other networks of, for example, multinational pharmaceutical companies, and gas, oil and mining industries, in different ways involved in or affected by the HIV pandemic. It is to the benefit of the companies to engage in prevention, treatment and care of the employees. In the many countries where there are no state health and social security systems, the companies have taken on the responsibility to care for employees and their families.

Socio-economic and demographic consequences

The socio-economic and demographic consequences are related to the fact that HIV as sexually transmitted hits people in their most productive ages, the young and strong; the breadwinners of families, the pillars of society, the thin layer of educated and trained people in a developing country such as teachers, doctors, nurses, engineers, administrators, lawyers, business leaders, entrepreneurs and skilled workers. In particular, it strikes the women who are carrying the burden of producing food out in the fields, caring for the children and nursing the sick family members. A key role of the parents is to teach the children life skills: how to survive, culture the land, care for the cattle and all the domestic tasks, do business, read, count and write, handle social contacts etc. As the parents die of AIDS, many children are abandoned and do not learn essential life skills. It will be still worse in the next generation and the next as the skills become more and more diluted. The World Bank has studied the consequences to the South African society after three generations, estimating that the gross national product will be halved during this century [40]. This is a tragedy not only to South Africa but the whole of Africa, for whom this well-developed country should be the engine pulling economy and development.

School education has a decisive importance for development, and is threatened by the high mortality amongst teachers. So many teachers succumb to AIDS each year in many African countries that it is impossible to train new teachers at the same rate. There is a similar problem with health care personnel, and apart from dying of AIDS, many move to Western countries with better working and living conditions and much higher salaries. The rich countries have been criticized for robbing poor countries of their investment in higher education and of much needed manpower to diminish the acute health care crisis caused by HIV/AIDS. The poor countries should be compensated for this drain.

Life expectancy has been dramatically shortened in the worst-affected countries. In Botswana, for instance, life expectancy increased steadily from the 1950s until the event of AIDS; it has now tumbled from 65 years to 35 years (see Fig. 7). The population pyramid in such countries has now been dramatically reshaped; it does not look like a pyramid any longer, but has a marked waistline for the age group 20–49 years, still with a broad base for the children and virtually unchanged for the elderly at the top.

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Figure 7.  Changes in life expectancy in selected African countries with a high and low HIV prevalence. Reproduced with kind permission of UNAIDS (2006).

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The economy has been hurt on all societal levels: the family economy due to illness and consequent lack of income, costs for medicine and traditional expensive funerals; the national economy due to loss of skill and trained manpower in agriculture, mining, oil and manufacturing industry, as well as a reduced willingness for foreign investments. The national budgets also suffer due to shrinking tax bases.

In the wake of the loss of the parent generation a large number of children have been orphaned. The extended African family can cope with losses of parents up to a certain level but not when several or perhaps all of aunts and uncles in a family also are dying. Then the burden of caring for the many children will be on the grandfathers and grandmothers, often already weakened by age. When they cannot cope any longer the older siblings or cousins will have to take care of the younger ones or the children will be abandoned to care for themselves, often as street children. They lack food, shelter, school education and protection against abuse and will be the first to be victims to HIV infection. UNAIDS has estimated that there are 11.4 million AIDS-orphans just in sub-Saharan Africa now, increasing to 25 million by 2010. All these orphans constitute a ticking social bomb, threatening to add to the destabilizing effect of HIV/AIDS in the worst affected countries. Eventually, as the very fabric of society breaks down, the survival of countries as orderly states is threatened.

Denial, disinformation and misconceptions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Biomedical overview
  5. Epidemiology
  6. Social and political aspects
  7. Denial, disinformation and misconceptions
  8. Discussion
  9. Conflict of interest statement
  10. References

AIDS as an emotionally loaded subject has attracted an astonishing amount of alternative theories. Already around 1983 a professor from the then communist East Berlin, Jacob Segal, launched an obscure theory that HIV was constructed by man from related viruses in sheep and cattle. This theory was allegedly planted as deliberate disinformation by the KGB during the cold war. It was said that HIV was produced by the CIA and wilfully spread in Africa, an idea that seems to attract people with conspiracy minds. In fact, there is no genetic similarity between HIV and the retroviruses of the animals mentioned, and besides, HIV existed already in the 1930s. It is also out of reach of science to create such a complicated virus. Still, the idea of HIV as manmade is still alive. For example, the winner of the Nobel Peace Prize in 2004, Wangari Maathai from Kenya, said that HIV is a biological weapon created by an evil scientist in the West in order to control the African population. In association with celebrations in Mozambique to mark 33 years of independence, Archbishop Francisco Chimoio was quoted by the BBC (26 September 2007) as saying that he believes some European-made condoms are infected with HIV deliberately. He also claimed that some anti-retroviral drugs were infected ‘in order to finish quickly the African people’.

Another myth that HIV was brought upon Africa by the West was presented by the British journalist Edward Hooper in his 1999 book The River. He claimed that HIV was spread during a trial with oral attenuated polio virus vaccine contaminated by chimpanzee SIV in the Congo in 1958. This is not consistent with the facts that the trial was in children, in whom no AIDS cases were reported, that HIV/SIV is not transmitted by the oral route, and that no retrovirus was found in the stored virus lot. Besides, chimpanzees were not used for the vaccine production.

The greatest harm has been created by an established scientist though, the molecular biologist Peter Duesberg, professor at Stanford University in California and member of the American National Academy of Science. Duesberg claims that AIDS is not caused by an infection, and certainly not by HIV, but by life style and predisposing conditions [41]. Many of the severe symptoms of AIDS, he says, are the side effects of antiretroviral drugs. Unfortunately, the South African President Thabo Mbeki has been attracted by these denialist ideas, preventing a rational approach to the HIV/AIDS epidemic in South Africa. This country has now developed the largest epidemic in the world, with more than 5 million people living with HIV and a thousand fatal cases a day. At the huge International AIDS Conference in the year 2000 in Durban, 5 000 scientists from all over the world published a declaration against these criminal ideas, which have been characterized as tantamount to genocide [42]. There are many followers of these ideas in the world, centred on a sect in California.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Biomedical overview
  5. Epidemiology
  6. Social and political aspects
  7. Denial, disinformation and misconceptions
  8. Discussion
  9. Conflict of interest statement
  10. References

Why have we not been able to control the pandemic?

In one sense, the global distribution of HIV can be characterized as a pandemic, but in another sense it can be seen as many separate epidemics. The latter is especially obvious when a separate subtype is spread within a specific area, for instance the spread of subtype C in South Africa after the downfall of apartheid in 1994 or the distribution of subtype E in Thailand (for discussion regarding designation of subtypes see [43–45]). Even the global distribution of subtype B amongst homosexual men could be considered as a separate epidemic. It is also a problem to compare the rapid global spread of an acute infection such as influenza with the persistent infection of HIV which is likely to continue decade after decade. Why then have we not succeeded in stopping the increasing spread of HIV on a global scale?

There are factors intrinsic to both the virus and the host organism which may help to explain. A major factor intrinsic to the virus is the sexual route of infection and the ability for vertical transmission from mother to child at birth and through breast milk.

Intrinsic to man is the urge for procreation and the insatiable hunger to live out sexuality which dominates over altruistic behaviour. To break transmission chains, a person who knows that he is HIV-infected is expected to abstain from sex or to use a condom. This can be considered unselfish, and unselfish behaviour is a utopian concept in terms of pure philosophy. Further, there seems to be a reflex-like tendency to oppress and exclude deviant individuals and groups, causing discrimination and stigmatization of people living with HIV/AIDS as well as of homosexual men and ethnic minorities. Gender domination is a major cause of the difficulties in controlling transmission; women often do not have the possibility to avoid being infected due to their dependency, culturally and economically. The reward system of the human brain makes man prone to intoxication by drugs, opening the transmission route of injected drug use. A universal human reaction in response to crisis is initial denial of serious threats. The problem in the case of AIDS is continued denial by some political leaders, which has delayed response in many regions of the world, such as in the USA, former Soviet Union, India and South Africa. Finally, man is not a rational being, emotions often win over knowledge. Therefore, information is important but has only limited value in changing risky behaviour. Due to all these factors, human nature constitutes a major obstacle to mastering the HIV epidemics.

Another reason for our shortcomings in halting further transmission may be an ethnocentric approach to the global HIV strategy. The initial measures to control the epidemics were based on Western knowledge and experience, notably the dramatic appearance of AIDS amongst homosexual men in the USA. Consideration for personal integrity took priority over public health measures. For instance, HIV testing and notification of public health authorities were not applied, nor partner notification. Instead activities were guided by summary reports of AIDS cases reflecting events that occurred about 10 years previously, which is totally irrational. Strategies centred on the individual did not work when imposed on cultures with different notions.

Bad governance has plagued many people, both in Africa as well as in Eastern Europe and Asia, during the course of the AIDS epidemics. Many political leaders do not care about the wellbeing of the people, but nurse their own power base and private fortune, as currently seen in countries such as Zimbabwe and North Korea. Due to the current world order, both the UN and individual donor countries have to go through national governments, and assistance often does not reach the people. Therefore, measures to prevent HIV transmission and to care for the infected and affected are not implemented, even if resources are put at disposal. Lack of political will and of infrastructure is causing an implementation crisis.

What can be done?

Good attempts and good intentions will not stop the epidemic; only a total and full-fledged attack will make a difference. Many successful projects have not been implemented and fully financed nationally. It is essential to scale up activities to full national coverage, otherwise we may be winning battles, but are losing the war.

Just as the wide spread of HIV depends on several factors, so the response has to be multifactorial. There is no ‘quick fix’. Information is one factor, but does not automatically lead to behavioural change and obviously has not made a lot of difference. Therefore, measures to influence decision-making need to be added that are not only based on rational thinking; techniques used in advertizing and public relations, religion and political life. Delay of sexual debut, reduction in the number of sexual partners and condom use are measures with proven effect. The effect of male circumcision on reducing transmission to women still needs further studies. Methods to further reduce mother-to child transmission during delivery and breastfeeding without creating drug resistance and side effects should be encouraged. HIV testing with counselling should be increased. It is hard to imagine any new revolutionary preventive measure which can be applied on a wide scale except microbicides and vaccines. Success in these two areas would mean great steps forward but would not be a final solution.

Further availability of antiretroviral treatment will save lives and suffering but will not stop the epidemic. At present, approximately 2.5 million people in low-mid-income countries are receiving antiretroviral therapy, but for every person who began antiretroviral treatment in 2006, six new people were infected. Thus we are further from universal access to treatment than before, highlighting the importance of improved prevention. People with treatment also live longer, and there have never been so many HIV infected as at the present time.

The most important measures are in the socio-economic sphere. By improving emancipation of women and raising the living conditions of the population at large, we are likely to reach the comparatively low HIV adult prevalence levels of North-Western Europe, Australia and New Zealand, that is 0.1–0.2%. It may be difficult to obtain a lower level in a sustainable way. Even this much will cost continued effort and might be unattainable, considering poverty, the lack of political leadership and the inherent tendency towards discrimination and stigmatization. Fortunately these negative qualities are counter-balanced by other inherent human qualities such as compassion and social cohesion.

Prospects for finding a cure

Successful treatment with antiretroviral drugs does not mean a cure. As soon as treatment is interrupted the production of new virus particles is resumed and the disease process continues. Science has made significant contributions to the fight against AIDS but it currently seems that we may have reached the limit of the quantum leaps. Drugs can still be improved to cause fewer side effects, to be simpler to use, to be less prone to provoke resistance, and to attack virus production in new ways, but it is difficult to think how it would be scientifically possible to offer a cure. Due to integration of the virus into the DNA of the host, it would be necessary to find a way to clear latent provirus without damaging the DNA of the infected cells, or at least to localize and kill all infected cells.

At present, it seems impossible to eradicate HIV in our bodies once the infection has been established. The virus remains dormant in long-lived white blood cells, and finds sanctuary in places which are difficult for drugs to penetrate, for instance certain brain cells. Furthermore, mutation leads to resistance to drug therapy, and it has not yet been possible to develop a vaccine.

However, trust in modern science is so great that people do not like to consider the thought that it may not be possible to find a cure or a vaccine against AIDS. The result is that not enough attention is given to social and economic development and the fight against discrimination, areas that are key to successfully responding to the epidemic.

Scenario for the future

HIV/AIDS may never disappear from mankind. The spread of HIV over the globe occurred unabated, seemingly following its natural course but modified by the circumstances, for instance the less favourable conditions (from the virus’ point of view) amongst the general population in industrialized countries. However, even in such countries, there are niches providing advantageous circumstances for transmission, e.g. amongst injecting drug users and underprivileged population groups, such as Afro-Americans and aboriginal minorities.

Probably the extremely high prevalence of 30–40% in productive ages occurring in some Southern African countries will decrease over time, as it already has in Eastern Africa, where after more than 20 years it remains between five and ten percent. Initially high incidence levels may be due to a combination of factors such as many new HIV infections resulting in high virus levels and corresponding high infectiousness, and many concurrent sexual partners between men and women. Will such intense transmission in the general population occur outside sub-Saharan Africa? Nobody can guarantee that it will not, but so far, in other regions HIV has mainly affected people with particular risk behaviour, such as injecting drug users and homosexual men. However, once HIV is prevalent enough in a society, it is difficult to control, as learnt from the current situation in Thailand with transmission in married couples.

‘Let the next generation be an AIDS-free generation’ is a hopeful but unfortunately unrealistic political slogan. HIV will not go away, as entrenched as it is in all countries of the world. Therefore, to use yet another stereotype, we have to learn how to ‘live with HIV/AIDS’. Civil society has a decisive role to play in raising awareness and pushing for change, for instance to radically raise the status of women and remove economic and judicial obstacles to emancipation. The success of the environmental movement in raising awareness of global warming constitutes a good example; it took some 30 years to reach the leaders of the world but we are finally there. The world cannot afford to wait another 30 years for an awakening about the ongoing AIDS catastrophe. Twenty-five years have already passed (Fig. 8).

image

Figure 8.  Major milestones in the history of HIV/AIDS.

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Footnotes
  • 1

    ‘People living with HIV’ is an example of recommended vocabulary according to UNAIDS terminology guidelines. Other recommended terms, with rationale, can be found at http://www.unaids.org in the publications section.

  • 2

    Cosponsors include UNHCR, UNICEF, WFP, UNDP, UNFPA, UNODC, ILO, UNESCO, WHO and the World Bank.

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  2. Abstract
  3. Introduction
  4. Biomedical overview
  5. Epidemiology
  6. Social and political aspects
  7. Denial, disinformation and misconceptions
  8. Discussion
  9. Conflict of interest statement
  10. References
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