HIV This Week

Hoffman RM, Umeh OC, Garris C, Givens N, Currier JS. Evaluation of Sex Differences of Fosamprenavir (With and Without Ritonavir) in HIV-Infected Men and Women. HIV Clin Trials. 2007; 8(6):371-80.

Recent studies focusing on HIV-1-infected women have suggested the existence of sex-related differences in natural history, antiretroviral pharmacokinetics, efficacy, and tolerability. This article analyzes three pivotal trials of the protease inhibitor (PI) fosamprenavir (FPV) with a view to providing a better understanding of potential sex differences in efficacy and safety. A post hoc, descriptive analysis was performed on data from 700 subjects (26% women) in three trials of FPV to evaluate sex differences with regard to efficacy, rates of discontinuation, and treatment-related adverse events. No major sex differences were found. Men and women had similarly good antiviral responses, with greater than 60% of treatment-naïve subjects achieving virologic suppression (<400 copies/mL) at 48 weeks. PI-experienced women in CONTEXT receiving once-daily FPV/r experienced the highest rates of discontinuations due to virologic failure (29% in women vs. 8% in men). Women generally had slightly lower rates of liver enzyme elevations and fewer abnormalities of total cholesterol and triglycerides. In conclusion, the absence of major sex differences provides reassurance, but the small number of women in these trials limited the ability to draw conclusions. Future trials should be specifically powered to detect sex differences in safety and efficacy.

Editors’ note: This retrospective analysis attempts to pull together data from three trials to overcome the low numbers of participating women. Finding no sex-based differences does not mean that these do not exist when studies are not designed to be able to detect them. The December 2007 Geneva consultation ‘Making HIV trials work for women and adolescent girls’ concluded that for clinical trials to include a scientifically meaningful number of women, a new norm in clinical trial conduct would need to be fostered.