Smith Kimberly Y, Tierney Camlin, Mollan Katie, Venuto Charles S, Budhathoki Chakra, Ma Qing, Morse Gene D, Sax Paul, Katzenstein David, Godfrey Catherine, Fischl Margaret, Daar Eric S, Collier Ann C
Department of Medicine Division of Infectious Diseases, Rush University Medical Center, Chicago, Illinois.
Clin Infect Dis. 2014 Feb;58(4):555-63. doi: 10.1093/cid/cit747. Epub 2013 Nov 18.
We aimed to evaluate treatment responses to atazanavir plus ritonavir (ATV/r) or efavirenz (EFV) in initial antiretroviral regimens among women and men, and determine if treatment outcomes differ by sex.
We performed a randomized trial of open-label ATV/r or EFV combined with abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC) in 1857 human immunodeficiency virus type 1-infected, treatment-naive persons enrolled between September 2005 and November 2007 at 59 sites in the United States and Puerto Rico. Associations of sex with 3 primary study endpoints of time to virologic failure, safety, and tolerability events were analyzed using Cox proportional hazards models. Model-based population pharmacokinetic analysis was performed using nonlinear mixed effects modeling (NONMEM version VII).
Of 1857 participants, 322 were women. Women assigned to ATV/r had a higher risk of virologic failure with either nucleoside reverse transcriptase inhibitor backbone than women assigned to EFV, or men assigned to ATV/r. The effects of ATV/r and EFV upon safety and tolerability risk did not differ significantly by sex. With ABC/3TC, women had a significantly higher (32%) safety risk compared to men; with TDF/FTC, the safety risk was 20% larger for women compared to men, but not statistically significant. Women had slower ATV clearance and higher predose levels of ATV compared to men. Self-reported adherence did not differ significantly by sex.
This is the first randomized clinical trial to identify a significantly earlier time to virologic failure in women randomized to ATV/r compared to women randomized to EFV. This finding has important clinical implications given that boosted protease inhibitors are often favored over EFV in women of childbearing potential.
NCT00118898.
我们旨在评估初治抗逆转录病毒治疗方案中，阿扎那韦联合利托那韦（ATV/r）或依非韦伦（EFV）对男性和女性的治疗反应，并确定治疗结果是否因性别而异。
我们在美国和波多黎各的59个地点，对1857例1型人类免疫缺陷病毒感染且未接受过治疗的患者进行了一项开放标签的随机试验，将ATV/r或EFV与阿巴卡韦/拉米夫定（ABC/3TC）或替诺福韦/恩曲他滨（TDF/FTC）联合使用。使用Cox比例风险模型分析性别与病毒学失败时间、安全性和耐受性事件这3个主要研究终点之间的关联。使用非线性混合效应模型（NONMEM版本VII）进行基于模型的群体药代动力学分析。
1857名参与者中，322名是女性。与分配至EFV组的女性或分配至ATV/r组的男性相比，分配至ATV/r组的女性使用任何一种核苷类逆转录酶抑制剂骨干方案时病毒学失败风险更高。ATV/r和EFV对安全性和耐受性风险的影响在性别上无显著差异。使用ABC/3TC时，女性的安全性风险比男性显著高（32%）；使用TDF/FTC时，女性的安全性风险比男性高20%，但无统计学意义。与男性相比，女性的ATV清除率较慢且ATV给药前水平较高。自我报告的依从性在性别上无显著差异。
这是第一项随机临床试验，发现与随机接受EFV治疗的女性相比，随机接受ATV/r治疗的女性病毒学失败时间显著更早。鉴于在有生育潜力的女性中，增强型蛋白酶抑制剂通常比EFV更受青睐，这一发现具有重要的临床意义。
NCT00118898。
