A number of alternative causes for AIDS have been put forward by critics of the HIV-AIDS link.

The most prominent and widely supported alternative theory is that AIDS is the consequence of different risk factors in different risk groups. Professor Peter Duesberg has argued that the AIDS epidemic in Europe and North America can be explained by the effects of long-term recreational drug use by gay men and drug users, and by the effects of blood products on the immune systems of haemophiliacs and transfusion recipients. Duesberg argues that the emergence of AIDS corresponds with the emergence, ten years earlier, of high levels of drug use amongst gay men and injecting drug users. These drugs (heroin, cocaine and amyl nitrite) are claimed to be capable of causing sufficient immune suppression and concomitant malnutrition.

Yet studies of the effects of all these drugs have not shown them to produce the distinctive depletion of CD4 lymphocytes characteristic of AIDS. These drugs do tend to depress all lymphocyte functions, but long-term users who are not HIV-positive show no signs of long-term declines in CD4 lymphocytes in all the comparative studies which have been performed (Schechter). HIV-positive people who use drugs do experience a long-term decline in CD4 lymphocytes. Is it more reasonable to infer that drugs or HIV are associated with the decline of CD4 lymphocytes in this case?

In the case of haemophiliacs Duesberg argues that cumulative exposure to Factor VIII rather than HIV is responsible for AIDS. Yet a number of studies have looked at cumulative exposure to Factor VIII among both HIV-positive and HIV-negative haemophiliacs and have found no difference between heavy users and minimal users of Factor VIII in immune status (Hassett; Becherer; Gjerset). One study has compared the incidence of AIDS in two groups of severe haemophiliacs who received very similar high levels of Factor VIII, one HIV-positive, one HIV-negative. Only the HIV-positive haemophiliacs in this study have developed AIDS, contradicting Duesbergs assertion that the dose of Factor VIII is the critical determinant of AIDS risk.

Among children infected with HIV at birth by blood transfusions, Duesberg has claimed that the true cause of illness was their pre-existing ill-health which necessitated the transfusion, or the immunosuppressive effects of the foreign blood proteins in the transfusion. Yet a study in the Netherlands of 11 infants infected with HIV at birth by small amounts of plasma from a single donor found no correlation between the severity of AIDS-related illnesses experienced by the infants during the following ten years and the clinical condition of the infants in the neonatal period or the volume of transfused plasma. Eight of the eleven infants died during the ten-year follow-up, and two of the surviving three have HIV-related symptoms (van den Berg).

Duesberg has also argued that AZT and other anti-retroviral drugs contribute to further immune suppression in those already diagnosed HIV-positive. Duesberg and many other dissidents put forward the view that nucleoside analogue drugs are immune suppressive because they suppress the production of new white blood cells in the bone marrow. This limits the ability of the immune system to produce CD4 lymphocytes. It is undoubtedly true that in the early years of AZT treatment, the high doses which were used caused damage to the bone marrow. However, this danger was recognised some years ago and the doses of AZT used in HIV therapy drastically reduced as it became clear that the drug still had an anti-retroviral effect at much lower doses which had little effect on bone marrow. A retrospective study of Europeans followed from the time of their AIDS diagnosis showed that those who had taken AZT were significantly less likely to have died after two years of treatment than people who remained untreated for two years after diagnosis. However, this advantage disappeared after two years and people who had received more than two years AZT treatment were significantly more likely to die than their counterparts who had gone untreated. The study does not explain whether there was any difference in the AIDS-defining illnesses experienced by the treated and untreated groups which might bias the results.

The argument that the cumulative effect of nucleoside analogue drugs is so harmful to the immune system that it leads to the development of AIDS took a further knock with the publication of the results of the Delta trial. This study evaluated the effects of combined treatment with two nucleoside analogues (AZT plus either ddI or ddC) compared with one (AZT alone). People who received combination therapy were less likely to develop AIDS-related symptoms or to die than people taking AZT monotherapy, a result which is the opposite to what would be expected if these drugs were really immunosuppressive. Since then, a further four clinical endpoint trials have shown that three drug therapy is clinically superior to dual therapy, which is the opposite result to that predicted by Duesberg's theory.

Critics of the HIV-AIDS link argue that AIDS in Africa can be explained by the high rate of parasitic infections, malnutrition, tuberculosis and the abuse of antibiotics, and that HIV antibodies are just markers for immune suppressive risk factors. However, there is widespread agreement amongst African doctors that whilst AIDS is a new syndrome, all these proposed causes have been present in Africa for many years before the emergence of AIDS.

A number of studies have compared the death rate in cohorts of HIV-positive and HIV-negative individuals who share the same risk factors, and all have shown that the risk of death is much greater for HIV-positive individuals than for HIV-negative individuals. In the UK an investigation of the medical records of all haemophiliacs alive between 1977 and 1991 showed that whilst the death rate amongst HIV-negative haemophiliacs who received a large number of Factor VIII infusions remained stable during the study, the death rate amongst HIV-positive severe haemophiliacs increased from 8 to 81 per 1,000 from 1984 to 1991(Darby).

An Italian study of 2,431 injecting drug users between 1985 and 1991 showed that HIV-positive individuals were 4.5 times more likely to die than HIV-negative individuals, and no deaths due to AIDS-defining illnesses were seen in the 1,661 HIV-negative individuals compared with 89 AIDS-related deaths amongst 770 HIV-positive individuals (Zaccarrelli).