Women account for an increasing proportion of patients with HIV-1 but remain underrepresented in antiretroviral clinical trials.
To evaluate sex-based differences in efficacy and adverse events in treatment-experienced HIV-positive women and men receiving darunavir–ritonavir-based therapy over 48 weeks.
Multicenter, open-label, phase IIIb study designed to enroll a high proportion of women, with sample size determined on the basis of a noninferiority design with a maximum allowable difference of 15% in virologic response favoring men. (Clinicaltrials.gov registration number: NCT00381303)
65 sites in the United States, Puerto Rico, and Canada.
287 women and 142 men.
Patients received darunavir–ritonavir, 600/100 mg twice daily, plus an investigator-selected optimized background regimen.
Virologic response (HIV-1 RNA <50 copies/mL using a time-to-loss of virologic response [TLOVR] algorithm) and adverse events were assessed over 48 weeks.
67% of patients were women; 84% of patients were black or Hispanic. A higher proportion of women discontinued treatment than men (32.8% vs. 23.2%; P = 0.042); more women than men discontinued for reasons other than virologic failure. Response rates in women and men at week 48 were 50.9% and 58.5%, respectively (intention-to-treat TLOVR), and 73.0% and 73.5%, respectively (TLOVR-censored for patients who withdrew for reasons other than virologic failure . The absolute difference in response, based on logistic regression and adjusted for baseline log10 viral load and CD4+ cell count, was −9.6 percentage points (95% CI, −19.9% to 0.7 percentage points;; P = 0.067) for intention-to-treat TLOVR and −3.9 percentage points (CI, −13.9% to 6.0 percentage points; P = 0.438) for TLOVR-population that censored patients who withdrew for reasons other than virologic failure. Adverse events were similar between the sexes. The most common grade 2 to 4 adverse events that were considered at least possibly treatment-related in women and men were nausea (5.2% and 2.8%, respectively), diarrhea (4.5% and 4.9%, respectively), and rash (2.1% and 2.8%, respectively).
Baseline characteristics differed between women and men.
Nonsignificant, sex-based differences in response were found during the 48 weeks of the GRACE study; however, these differences were probably due to higher discontinuation rates in women, suggesting that additional efforts are needed to retain women in clinical trials.
Primary Funding Source