Efficacy of zidovudine treatment in homosexual men with AIDS-related complex

Abstract

To investigate (1) the efficacy and safety of zidovudine treatment in homo-/bisexual men with AIDS-related complex (ARC) and (2) factors associated with development of intolerance to zidovudine. A multicentre open-label study. Australian public hospital system. A total of 235 homo-/bisexual men with ARC were enrolled. All subjects received 1200 mg zidovudine daily. Survival, incidence and time to development of AIDS and to development of haematological and clinical side-effects. Median time to development of AIDS was 61 weeks, significantly longer (P < 0.03) than the median of 22 weeks in a small control group of 12 untreated ARC subjects. Median survival from development of AIDS was 48 weeks, marginally longer than the 44 weeks in untreated historical AIDS controls. Anaemia requiring transfusion occurred in 113 subjects (48%). Significant differences in time to development of AIDS were found in favour of subjects not requiring transfusions (P < 0.001) with no weight loss (P = 0.004), and who received the full zidovudine dose (1200 mg) during the first 52 weeks of treatment (P = 0.021). Significantly longer median survival times from commencement of zidovudine were found in subjects with a baseline Karnofsky score > or = 90, baseline Hb > or = 13 g/dl, baseline CD4+ cell count > or = 50 x 10(6)/l, no weight loss during first year of treatment, and no or not more than one blood transfusion during treatment. The ability to tolerate full-dose zidovudine was best predicted by a baseline Hb > or = 13 g/dl. Zidovudine-intolerant subjects (defined as the development of either anaemia requiring transfusions, WCC 1000 x 10(6)/l or zidovudine-related myopathy) had a significantly shorter time to development of AIDS than zidovudine-tolerant subjects (P = 0.002). Zidovudine may benefit people with ARC by significantly postponing the development of AIDS. This benefit appears to be greater in those who do not develop clinical intolerance whilst receiving zidovudine. However, administration of zidovudine to subjects with ARC does not appear to contribute to improved survival after the development of AIDS. People with ARC who develop AIDS while receiving zidovudine, or who develop intolerance to zidovudine, should be considered immediately eligible for other antiretroviral therapies.