Sex Differences in Antiretroviral Therapy Toxicity: Lactic Acidosis, Stavudine, and Women

Abstract

Lactic acidosis a serious complication of treatment with nucleoside analogue reverse-transcriptase inhibitors was first reported in patients with HIV infection 115 years ago. Initial reports included patients treated with didanosine and zidovudine but it later became clear that treatment with stavudine was most closely associated with this complication. A common finding in the literature describing case series of nucleoside analogue reverse-transcriptase inhibitor-related lactic acidosis has been the over-representation of women (who accounted for 83% of cases in 1 series) especially obese women. Sex-specific event rates for lactic acidosis were not calculated in earlier series because of limited prospective data; however given the relatively low proportion of women in HIV care in the mid-1990s in the United States and Europe one can imagine that the female-specific incidence rates were very high. Because of the fact that 150% of people with HIV infection in sub-Saharan Africa are women the high rates of lactic acidosis being reported in recent data from antiretroviral treatment programs in South Africa should not come as a surprise. Geddes et al. reported 14 cases of lactic acidosis among 891 patients receiving treatment with stavudine lamivudine and a nonnucleoside reverse-transcriptase inhibitor. In their series all 14 cases of lactic acidosis occurred among obese women with a median weight of 81 kg. The overall incidence rate was 19 cases per 1000 patient-years; however this rate included both men and women in the denominator. (excerpt)