在一项IIb期试验中，多韦拉韦剂量选择及与依非韦伦相比在初治HIV-1感染成人抗逆转录病毒治疗中的96周安全性和疗效
Doravirine dose selection and 96-week safety and efficacy versus efavirenz in antiretroviral therapy-naive adults with HIV-1 infection in a Phase IIb trial.
作者信息
Gatell Jose M, Morales-Ramirez Javier O, Hagins Debbie P, Thompson Melanie, Arastéh Keikawus, Hoffmann Christian, Raffi François, Osiyemi Olayemi, Dretler Robin, Harvey Charlotte, Xu Xia, Plettenberg Andreas, Smith Don E, Portilla Joaquín, Rugina Sorin, Kumar Sushma, Frobose Colleen, Wan Hong, Rodgers Anthony, Hwang Carey, Teppler Hedy
机构信息
Hospital Clinic/IDIBAPS, University of Barcelona, Barcelona, Spain.
Present address: ViiV Healthcare, Barcelona, Spain.
出版信息
Antivir Ther. 2019;24(6):425-435. doi: 10.3851/IMP3323.
BACKGROUND
The safety and efficacy of doravirine were compared with that of efavirenz as initial treatment of adults living with HIV-1 infection (NCT01632345).
METHODS
A Phase IIb double-blind trial with participants stratified by screening HIV-1 RNA (≤ or >100,000 copies/ml) and randomized 1:1:1:1:1 to receive once-daily doravirine (25, 50, 100 or 200 mg) or efavirenz 600 mg (Part I) for up to 96 weeks, with open-label tenofovir disoproxil fumarate 300 mg/emtricitabine 200 mg (TDF/FTC). After dose selection at week 24, doravirine 100 mg was provided to participants receiving the other doses of doravirine and additional participants were randomized 1:1 to receive once-daily doravirine 100 mg or efavirenz 600 mg for 96 weeks with TDF/FTC (Part II). Primary outcomes were the proportion of participants with HIV-1 RNA <40 copies/ml at week 24, and central nervous system (CNS) adverse events (AEs) by weeks 8 and 24 (Parts I+II combined).
RESULTS
210 and 132 participants were randomized in Parts I and II, respectively, and 216 (108 on doravirine 100 mg, 108 on efavirenz) were evaluable for Parts I+II combined. At week 24, the proportion of participants with HIV-1 RNA <40 copies/ml was 72.9% for doravirine 100 mg and 73.1% for efavirenz (difference -0.5 [95% CI -12.3, 11.2]). In addition, CNS AEs were reported by 26.9% and 47.2% of doravirine and efavirenz recipients, respectively (difference -20.4 [95% CI -32.6, -7.5]; P=0.002).
CONCLUSIONS
Doravirine 100 mg with TDF/FTC demonstrated similar antiretroviral activity and superior CNS safety compared with efavirenz 600 mg with TDF/FTC.
背景
比较了多韦拉韦与依非韦伦作为成人HIV-1感染者初始治疗药物的安全性和有效性（NCT01632345）。
方法
一项IIb期双盲试验，参与者根据筛查时的HIV-1 RNA水平（≤或>100,000拷贝/毫升）分层，并按1:1:1:1:1随机分组，接受每日一次的多韦拉韦（25、50、100或200毫克）或依非韦伦600毫克（第一部分），持续96周，同时服用开放标签的替诺福韦酯300毫克/恩曲他滨200毫克（TDF/FTC）。在第24周进行剂量选择后，为接受其他剂量多韦拉韦的参与者提供100毫克多韦拉韦，并将额外的参与者按1:1随机分组，接受每日一次的100毫克多韦拉韦或600毫克依非韦伦，同时服用TDF/FTC，持续96周（第二部分）。主要结局指标为第24周时HIV-1 RNA<40拷贝/毫升的参与者比例，以及第8周和第24周时的中枢神经系统（CNS）不良事件（AE）（第一部分和第二部分合并）。
结果
第一部分和第二部分分别有210名和132名参与者被随机分组，216名（108名接受100毫克多韦拉韦，108名接受依非韦伦）可纳入第一部分和第二部分合并分析。在第24周时，接受100毫克多韦拉韦的参与者中HIV-1 RNA<40拷贝/毫升的比例为72.9%，接受依非韦伦的参与者中该比例为73.1%（差异为-0.5[95%置信区间-12.3,11.2]）。此外，接受多韦拉韦和依非韦伦的参与者中分别有26.9%和47.2%报告了CNS AE（差异为-20.4[95%置信区间-32.6,-7.5]；P=0.002）。
结论
与600毫克依非韦伦联合TDF/FTC相比，100毫克多韦拉韦联合TDF/FTC显示出相似的抗逆转录病毒活性和更好的CNS安全性。
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