Infections amongst haemophiliacs in the United States began as early as 1978, which explains why haemophiliac cases emerged so swiftly after the first cases in gay men. The first haemophiliacs were infected at the same time as the first wave of gay men in large cities like San Francisco. AIDS cases amongst haemophiliacs were never clustered in one area however, because Factor VIII concentrates were produced with blood from thousands of donors.

Studies have shown that those haemophiliacs who received the largest quantities of non heat–treated blood (invariably those suffering from more severe forms of haemophilia) were more likely to have been infected with HIV. Age was less significant than the quantity of clotting factor received (Gjerset). A small study amongst haemophiliacs in the UK has shown that immune suppression prior to being treated with a batch of HIV–infected Factor VIII increased the likelihood that an individual would be infected (Madhok). Subsequent studies have shown that a highly purified form of Factor VIII produced with the aid of monoclonal antibodies seems to reduce the level of immunological abnormalities (De Biasi).

Some commentators have interpreted these findings as proof that HIV does not cause AIDS in haemophiliacs, and that the syndrome is a consequence of the immunosuppressive effects of Factor VIII therapy. They argue that HIV antibodies correlate only with the highest level of exposure to Factor VIII.

This view is refuted by epidemiological study of HIV infection and AIDS amongst European haemophiliacs (Kroner). Clear differences can be observed in HIV prevalence and subsequent diagnoses of AIDS between haemophiliacs exposed to Factor VIII derived from United States donors and European donors. In Germany and Austria for instance, a large number of seroconversions are estimated to have occurred as a consequence of the continued use of US derived plasma throughout 1983. Furthermore, the introduction of heat treatment has eliminated the risk of HIV infection; there have been no recorded seroconversions in individuals seronegative up until the time that heat treatment was introduced, apart from the recipients of one batch of Factor VIII recalled by a manufacturer following the discovery that the clotting factor had been inadequately heat–treated.

Furthermore, a study of British haemophiliacs has shown that HIV–positive haemophiliacs followed between 1979 and 1992 had a tenfold greater chance of death than their HIV–negative counterparts, and the excess of deaths in the HIV–positive group was accounted for by AIDS–related illnesses and various forms of liver disease (Darby).

Claims that a large proportion of French haemophiliacs were infected whilst the French authorities used up stocks of non heat–treated Factor VIII are probably incorrect however; a 1994 study estimates that 93.2% of those French haemophiliacs who seroconverted had done so by the time this dispute began (Kroner).

The subsequent incidence of AIDS amongst HIV–positive haemophiliacs raises questions concerning the likelihood that AIDS will develop amongst this group. After having been infected for twelve years, haemophiliacs are less likely to have developed AIDS than those in other risk groups. There may be a number of explanations for this:

• it has been shown that treatment with very high purity Factor VIII slows or halts CD4 decline in several studies of HIV–positive haemophiliacs (de Biasi).
• age at seroconversion is a strongly associated with disease progression and survival: men with haemophilia in the UK under 15 at seroconversion are significantly more likely to be alive after twelve years than men with haemophilia aged 55 or over at seroconversion.
• It may also be the case that co–factors which affect other groups such as sexually transmitted infections or drug injecting are absent in this group.

The UK response to contamination of Factor VIII

In 1984 testing for HIV became available. By the end of June 2005, 1362 of the estimated 5,000 British people with haemophilia had been infected. This represents about one quarter of the entire haemophilia community. However, up to 60% of those with severe haemophilia had been infected.

At the end of 1984 all American Factor VIII had been heat treated to clear it of viruses. Britain followed suit in 1985, after which all people with haemophilia, regardless of HIV antibody status, should have been treated with heat treated product.

How safe is Factor VIII now?

Blood donations are routinely tested for HIV, and blood products are treated to destroy known viral contaminants.

Heat treatment has to be carried out carefully on account of the fragility of the Factor VIII molecule. Time has shown that heat treatment effectively eliminates HIV from blood products.

In 1984 an international committee stated there was a `lack of uniformity and rational methodological approach of clinical evaluation' and since then, more useful studies have been conducted. British factor VIII is lyophilised (freeze dried – like coffee) and then heat-treated. A study of patients receiving this found none to be infected with hepatitis C – which was used as a marker for viral infection.

A more definitive test was done on German Factor VIII, which is pasteurised, and of 155 people with haemophilia given this, none were found to have become infected with HIV.

More modern technologies involving monoclonal antibodies or ion exchange chromatography have rendered blood products as safe as current scientific knowledge permits.

By 1989 the UK was largely self–sufficient in voluntarily donated heat treated product. Although 20% of product is still imported (by clinical choice) from international pharmaceutical companies, these concentrates are manufactured primarily from paid donors, but are tested and/or treated before use in the UK.

The risks of having been infected

The risk of having been infected with HIV for haemophiliacs is related to:

• Whether you received contaminated blood product concentrate; this is less likely after 1985 or before that date if you only received single donor agents like cryoprecipitate; your Haemophilia Centre should have a record of this.
• Whether you ever shared needles with someone who had HIV.
• Whether you have had unsafe sex with someone who has HIV.

References

De Biasi R et al: The impact of a very high purity factor VIII concentrate on the immune system of human immunodeficiency virus–infected haemophiliacs: a randomized, prospective, two–year comparison with an intermediate purity concentrate, Blood 78(8): 1919–1922, 1991.

Chelucci C et al: PCR analysis of HIV–1 sequences and differential immunological features in seronegative and seropositive haemophiliacs, Br J Haematology 81: 558–567, 1992.

Cuthbert RJ et al: Immunological studies in HIV seronegative haemophiliacs: relationships to blood product therapy, Br J Haematology 80: 364–369, 1992.

Gjerset GF et al: Treatment type and amount influenced human immunodeficiency virus seroprevalence of patients with congenital bleeding disorders, Blood 78(6): 1623–1627, 1991.

Kroner BL et al: HIV–1 infection among persons with haemophilia in the United States and Western Europe, 1978–1990,  JAIDS 7: 279–286, 1994.

Ludlam CA et al: Human lymphotropic virus type III (HTLV–III) infection in seronegative haemophiliacs after transfusion of Factor VIII, Lancet 8449: 233–236, 1985.

Madhok R et al: Impaired cell mediated immunity in haemophilia in the absence of infection with human immunodeficiency virus, BMJ 293: 978–980, 1986.