Firnhaber Cynthia, Smeaton Laura M, Grinsztejn Beatriz, Lalloo Umesh, Faesen Sharla, Samaneka Wadzanai, Infante Rosa, Rana Aadia, Kumarasamy Nagalingeswaran, Hakim James, Campbell Thomas B
HIV Clin Trials. 2015 May-Jun;16(3):89-99. doi: 10.1179/1528433614Z.0000000013. Epub 2015 May 15.
Worldwide, 50% of human immunodeficiency virus (HIV)-infected people are women. This study was to evaluate whether the safety and efficacy outcomes of three initial antiretroviral regimens (ARVs) differed by sex.
Antiretroviral regimen naive participants from nine countries in four continents were assigned to ARVs with efavirenz (EFV) plus lamivudine-zidovudine, atazanavir (ATV) plus didanosine (ddI)-EC/emtricitabine (FTC) or EFV plus FTC-tenofovir-DF. The primary objective was to estimate the sex difference on efficacy outcome of treatment failure defined as one of the following: 1. Time to 1st of confirmed virologic failure, 2. WHO Stage 4 progression or 3. death with hazard ratio (HR) and 95% confidence interval (CI) from adjusted Cox regression models.
In all, 739 (47%) women and 832 (53%) men with HIV were evaluated. Women had higher pretreatment CD4+(182 vs 165 cells/mm(3); P < 0.001) and lower HIV-1 RNA (4.9 log10 vs 5.2 log10 copies/ml; P < 0.001) compared to men. Association of sex with time to regimen failure differed by treatment arm (P = 0.018). For atazanavir plus didanosine-EC plus emtricitabine, women had a longer time to treatment failure compared to men [adjusted HR (aHR) = 0.59; 95% CI 0.40-0.87]. Women were less likely to prematurely discontinue treatment prematurely (aHR = 0.74; 95% CI 0.56-0.98). Women assigned to efavirenz plus lamivudine-zidovudine were more likely to have a primary safety event compared to men (aHR = 1.49; 95% CI 1.18-1.88).
Antiretroviral efficacy and safety differed by sex in this study. Consideration of potential effects of sex on antiretroviral outcomes is important for the design of future clinical trials and for HIV treatment guidelines.
在全球范围内，感染人类免疫缺陷病毒（HIV）的人群中有50%为女性。本研究旨在评估三种初始抗逆转录病毒治疗方案（ARV）的安全性和疗效结果是否因性别而异。
来自四大洲9个国家的初治抗逆转录病毒治疗方案参与者被分配接受以下抗逆转录病毒治疗方案：依非韦伦（EFV）加拉米夫定 - 齐多夫定、阿扎那韦（ATV）加去羟肌苷（ddI）肠溶胶囊/恩曲他滨（FTC）或EFV加FTC - 替诺福韦酯（TDF）。主要目的是通过调整后的Cox回归模型估计治疗失败疗效结果的性别差异，治疗失败定义为以下情况之一：1. 首次确认病毒学失败的时间；2. 世界卫生组织4期疾病进展；3. 死亡，并计算风险比（HR）和95%置信区间（CI）。
总共评估了739名（47%）感染HIV的女性和832名（53%）男性。与男性相比，女性治疗前CD4+细胞计数更高（182对165个细胞/mm³；P < 0.001），HIV - 1 RNA水平更低（4.9 log10对5.2 log10拷贝/ml；P < 0.001）。性别与治疗方案失败时间的关联因治疗组而异（P = 0.018）。对于阿扎那韦加去羟肌苷肠溶胶囊加恩曲他滨方案，与男性相比，女性治疗失败时间更长[调整后风险比（aHR）= 0.59；95% CI 0.40 - 0.87]。女性过早停止治疗的可能性较小（aHR = 0.74；95% CI 0.56 - 0.98）。与男性相比，接受依非韦伦加拉米夫定 - 齐多夫定治疗的女性发生主要安全事件的可能性更大（aHR = 1.49；95% CI 1.18 - 1.88）。
本研究中抗逆转录病毒治疗的疗效和安全性因性别而异。在未来临床试验设计和HIV治疗指南制定中，考虑性别对抗逆转录病毒治疗结果的潜在影响很重要。
