University of California, Los Angeles, CA, USA.
Ann Intern Med. 2010 Sep 21;153(6):349-57. doi: 10.7326/0003-4819-153-6-201009210-00002.
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 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 darunavir-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%; P = 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 log(10) 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 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.
女性在 HIV-1 患者中所占比例不断增加，但在抗逆转录病毒临床试验中代表性不足。
评估接受达芦那韦-利托那韦治疗的有治疗经验的 HIV 阳性女性和男性在 48 周时的疗效和不良事件是否存在性别差异。
多中心、开放性标签、3b 期研究，旨在招募大量女性，样本量根据非劣效性设计确定，最大允许男性病毒学应答优势差异为 15%。（临床试验.gov 注册号：NCT00381303）
美国、波多黎各和加拿大的 65 个地点。
287 名女性和 142 名男性。
患者接受达芦那韦-利托那韦，600/100mg，每日两次，加用研究者选择的优化背景治疗方案。
48 周时的病毒学应答（使用病毒学应答丢失时间[TLOVR]算法时 HIV RNA<50 拷贝/mL）和不良事件。
67%的患者为女性；84%的患者为黑种人或西班牙裔。与男性相比，更多的女性停止治疗（32.8%比 23.2%；P=0.042）；更多的女性因病毒学失败以外的原因停止治疗。48 周时，女性和男性的应答率分别为 50.9%和 58.5%（意向治疗 TLOVR）和 73.0%和 73.5%（排除因病毒学失败以外的原因而退出的患者的 TLOVR 分析）。基于逻辑回归并根据基线对数 10 病毒载量和 CD4+细胞计数进行调整，应答的绝对差异为-9.6 个百分点（95%CI，-19.9 至 0.7 个百分点；P=0.067），用于意向治疗 TLOVR，为-3.9 个百分点（95%CI，-13.9 至 6.0 个百分点；P=0.438），用于 TLOVR 人群，排除因病毒学失败以外的原因而退出的患者。性别之间的不良事件相似。女性和男性中最常见的 2 至 4 级不良事件，被认为至少与治疗有关的是恶心（分别为 5.2%和 2.8%）、腹泻（分别为 4.5%和 4.9%）和皮疹（分别为 2.1%和 2.8%）。
性别之间存在基线特征差异。
在 48 周的研究中发现了无统计学意义的、基于性别的应答差异；然而，这些差异可能归因于女性的停药率较高，这表明需要采取额外的措施来保留女性参与临床试验。
