Nucleoside Reverse Transcriptase Inhibitors

Although the incidence of HIV infection among women is increasing, the proportion of women in clinical trials that evaluate interventions for the treatment of HIV infection and its complications has historically been lower than the proportion of women in the HIV/AIDS patient population. Therefore, most knowledge about the efficacy of antiretroviral drugs and the adverse reactions associated with their use has been derived from studies involving predominantly male subjects. A review of female participation in large, multicenter clinical trials found that only 6.7% of the 11,909 AIDS Clinical Trials Group (ACTG) study participants from 1987 through 1990 were women. As a result of the relatively small number of female subjects in earlier HIV clinical trials, little is known about the influence of sex on the natural history of HIV infection and on the incidence and characteristics of adverse drug effects. Since a 1994 change in the National Institutes of Health policy on the enrollment of human subjects in clinical trials, more women have been involved in HIV-related studies. The proportion of women enrolled in ACTG-funded studies increased from 5.6% in 1987 to 16.9% in 1996. Current estimates are that approximately 20% of participants in ACTG clinical trials are women. However, the proportion of women in these trials still lags behind the proportion (25%) of reported AIDS cases in the United States that occur among women. In addition, several multicenter studies have enrolled exclusively women with or at risk of HIV infection. Examples include the Women’s Interagency HIV Study (WIHS), with 2066 HIV-seropositive and 575 HIV-seronegative women; the HIV Epidemiology Research Study (HERS), with 863 HIV-seropositive and 430 HIV-seronegative women; and the Women and Infants Transmission Study (WITS), with 2336 HIV-seropositive women and 1887 infants. Data from several of these studies suggest that sex differences may exist in several aspects of HIV infection and its management, including differences in the tolerability of some antiretroviral drugs. This article reviews the incidence and characteristics of sex differences in adverse reactions to antiretroviral drugs used to treat HIV infection.