Judith Currier, MD, MSc; Dawn Averitt Bridge, BIS; Debbie Hagins, MD; Carmen D. Zorrilla, MD; Judith Feinberg, MD; Robert Ryan, MSc; Ron Falcon, MD; Alan Tennenberg, MD, MPH; Joseph Mrus, MD, MSc; Kathleen Squires, MD; on behalf of the GRACE (Gender, Race, And Clinical Experience) Study Group
Currier J, Averitt Bridge D, Hagins D, Zorrilla CD, Feinberg J, Ryan R, et al. Sex-Based Outcomes of Darunavir–Ritonavir Therapy: A Single-Group Trial. Ann Intern Med. 2010;153:349-357. doi: 10.7326/0003-4819-153-6-201009210-00002
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Published: Ann Intern Med. 2010;153(6):349-357.
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 darunavirâ€“ritonavir therapy over 48 weeks.
Multicenter, open-label, phase 3b 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 darunavirâ€“ritonavir, 600/100 mg twice daily, plus an investigator-selected optimized background regimen.
Virologic response (HIV 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%; PÂ = 0.042); more women than men discontinued treatment 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 âˆ’9.6 percentage points (95% CI, âˆ’19.9 to 0.7 percentage points; PÂ = 0.067) for intention-to-treat TLOVR and âˆ’3.9 percentage points (CI, âˆ’13.9 to 6.0 percentage points; PÂ = 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 sexes.
Nonsignificant, sex-based differences in response were found during the 48-week 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.
Women remain underrepresented in clinical trials of antiviral drugs for treatment of HIV infection, limiting statistical power to determine differences in efficacy and adverse events.
Treatment-experienced, HIV-positive women were recruited to a clinical trial of darunavir–ritonavir in sufficient proportions to permit analysis by sex. No statistically significant differences between women and men were found in either treatment efficacy or occurrence of clinically relevant adverse events. However, women were more likely to discontinue study participation for reasons other than virologic failure.
Women and men differed in some baseline characteristics.
Women with HIV can be successfully recruited to clinical trials in sufficient proportions to permit analysis by sex. However, they may face unique barriers to clinical trial participation that result in higher rates of study discontinuation.
* “Other” classification was selected by the investigator as the reason for discontinuation.
† Older patient taking too many concomitant medications.
Virologic response was defined as viral load less than 50 copies/mL, confirmed by 2 consecutive assessments at least 14 days apart. ITT = intention-to-treat; TLOVR = time-to-loss of virologic response; VF = virologic failure.
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