Sex differences in antiretroviral therapy-associated intolerance and adverse events

Although women account for a substantial proportion of the global population infected with HIV, most clinical trials evaluating the safety and efficacy of specific antiretroviral therapy regimens have been preformed in predominantly male cohorts. Our knowledge of the sex differences associated with responses to these treatments is therefore limited. Potentially sex-specific influences, such as endogenous or exogenous hormones, could impact antiretroviral tolerance. Women also have different pharmacokinetic profiles for selected antiretrovirals compared with men. These factors could influence how women respond and react to antiretrovirals. Several observational studies have described a higher frequency of antiretroviral-related adverse effects among women compared with men. Women appear to be at an especially high risk for lactic acidosis, nevirapine-associated rashes and hepatotoxicity, and fat redistribution after highly active antiretroviral therapy exposure. Although a statistical association between antiretroviral toxicity and pregnancy has not been described, pregnancy may provide an additional influence on the toxicity of several antiretrovirals or antiretroviral combinations. Potential tolerability should be an important component in discussions of antiretroviral options among women.