Background:  Delineating potential gender differences in response to ART is important to HIV clinical care, research, and drug development. Cumulative data and analyses from HIV randomized clinical trials (RCT) could provide clinical, scientific, and regulatory benefits.

Methods:  From 2000 to 2008, datasets for registrational HIV RCT were evaluated for any gender differences in week 48 efficacy outcomes, defined as HIV RNA <400 copies/mL and differences in treatment effect size. Studies were stratified by treatment-naïve (TN) or treatment-experienced (TE) patient populations. Efficacy analyses by ARV class were also performed for NRTI, NNRTI, PI, fusion inhibitors (FI), and CCR5 inhibitors (CCR5).

Results:  The combined database had 17,826 HIV-infected subjects in 38 RCT for 14 ARV. There were no clinically or statistically significant gender differences in week 48 efficacy outcomes (assuming mean effect size difference between males and females were equal, the estimated 95% confidence interval (CI) of equal mean effect size difference:  –0.07, 0.09). For TN patients, the estimated 95%CI of equal mean effect size difference between males and females included zero (95%CI –0.1 to 0.09). For TE patients, the estimated 95%CI also included zero (95%CI –0.095 to 0.16). For all ARV classes analyzed, the estimated 95%CI included zero (NRTI, 95%CI –0.15 to 0.11; NNRTI, 95%CI –0.29 to 0.35; PI, 95%CI –0.08 to 0.13; FI, 95%CI –0.50 to 0.37; CCR5, 95%CI –0.46 to 0.50).

Conclusions:  Preliminary analyses of the FDA database are the most detailed review of gender-related ARV efficacy data so far. These analyses suggest no clinically or statistically significant gender differences in week-48 efficacy outcomes, regardless of treatment history, or drug class. Such data could help healthcare providers and HIV-1-infected patients when considering different ARV regimens. From scientific and regulatory perspectives, the cumulative data could help identify issues requiring additional investigation.