The effect of antiviral therapy on the natural history of human immunodeficiency virus infection in a cohort of hemophiliacs

Abstract

The antiviral drug zidovudine (ZDV) slows progression to AIDS and improves survival after AIDS diagnosis. Although clinical trials have demonstrated early improvement in CD4 lymphocyte number with ZDV, long-term effects of ZDV on CD4 in advanced and asymptomatic disease are not well known. The purpose of this study was to quantitate the effect of ZDV on the natural history of HIV infection, specifically the type and frequency of new AIDS cases, AIDS-free survival, survival after AIDS, and long-term change in an immunologic marker, CD4 number, in hemophiliacs. A cohort of 84 HIV(+) hemophiliacs for whom seroconversion dates and clinical outcomes are known was prospectively observed for the time to AIDS, pattern of primary AIDS diagnosis, rate of fall in CD4 lymphocyte levels AIDS-free survival, and survival after AIDS diagnosis. The frequency of new AIDS cases has slowed since 1989, with Pneumocystis carinii pneumonia (PCP) less common (15 vs. 52%, p less than 0.04) and non-PCP opportunistic infection more common (54 vs. 20%, p less than 0.07) than prior to 1989. Patients treated with ZDV before AIDS was diagnosed (n = 39) experienced a longer AIDS-free survival than untreated patients (n = 45), as 25% progressed to AIDS by 8.2 years compared with 4.5 years, respectively, p = 0.0013. Median survival after AIDS among those untreated was significantly shorter than among those treated with ZDV either before or after AIDS was diagnosed, 0.5, 2.8, and 2.1 years, respectively, p = 0.0005. Despite these clinical advantages, there was little difference in the rate of fall in CD4 lymphocyte number between ZDV-treated and untreated groups.(ABSTRACT TRUNCATED AT 250 WORDS)