多替拉韦/拉米夫定/富马酸替诺福韦二吡呋酯（TDF）与依非韦伦/恩曲他滨/TDF 在初治人类免疫缺陷病毒 1 型感染成人中的比较：随机、双盲、III 期 DRIVE-AHEAD 非劣效性试验的第 96 周结果。

Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial.

机构信息

Queen Mary University of London, London, United Kingdom.

Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

出版信息

Clin Infect Dis. 2021 Jul 1;73(1):33-42. doi: 10.1093/cid/ciaa822.

BACKGROUND

Doravirine (DOR) is a nonnucleoside reverse-transcriptase inhibitor. In the phase 3 DRIVE-AHEAD trial in treatment-naive adults with human immunodeficiency virus type 1 (HIV-1) infection, DOR demonstrated noninferior efficacy compared with efavirenz (EFV) and superior profiles for neuropsychiatric tolerability and lipids at 48 weeks. We present data through week 96.

METHODS

DRIVE-AHEAD is a phase 3, multicenter, double-blind, noninferiority trial in antiretroviral treatment-naive adults with HIV-1 RNA ≥1000 copies/mL. Participants were randomized to a daily fixed-dose tablet of DOR (100 mg), lamivudine (3TC; 300 mg) and tenofovir disoproxil fumarate (TDF; 300 mg) (DOR/3TC/TDF) or EFV (600 mg), emtricitabine (FTC; 200 mg) and TDF (300 mg) (EFV/FTC/TDF). The efficacy end point of interest at week 96 was the proportion of participants with HIV-1 RNA levels <50 copies/mL (Food and Drug Administration Snapshot Approach) with a predefined noninferiority margin of 10% to support week 48 results. Safety end points of interest included prespecified neuropsychiatric adverse events and the mean change in fasting lipids at week 96.

RESULTS

Of 734 participants randomized, 728 received study drugs and were included in analyses. At week 96, HIV-1 RNA <50 copies/mL was achieved by 77.5% of DOR/3TC/TDF vs 73.6% of EFV/FTC/TDF participants, with a treatment difference of 3.8% (95% confidence interval, -2.4% to 10%). Virologic failure rates were low and similar across treatment arms, with no additional resistance to DOR observed between weeks 48 and 96. Prespecified neuropsychiatric adverse events and rash were less frequent in DOR/3TC/TDF than in EFV/FTC/TDF participants through week 96. At week 96, fasting low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol (HDL-C) levels increased in the EFV/FTC/TDF group but not in the DOR/3TC/TDF group; the mean changes from baseline in total cholesterol/HDL-C ratio were similar.

CLINICAL TRIALS REGISTRATION

NCT02403674.

背景

多伟拉韦（DOR）是一种非核苷类逆转录酶抑制剂。在治疗初治的人类免疫缺陷病毒 1 型（HIV-1）感染者的 3 期 DRIVE-AHEAD 试验中，与依非韦伦（EFV）相比，DOR 显示出非劣效性，并且在 48 周时具有更好的神经精神耐受性和脂质特征。我们目前提供的是 96 周的数据。

方法

DRIVE-AHEAD 是一项 3 期、多中心、双盲、非劣效性试验，入组的是 HIV-1 RNA≥1000 拷贝/ml 的初治抗逆转录病毒治疗的成年人。参与者被随机分配至每日固定剂量的 DOR（100mg）、拉米夫定（3TC；300mg）和富马酸替诺福韦二吡呋酯（TDF；300mg）（DOR/3TC/TDF）或 EFV（600mg）、恩曲他滨（FTC；200mg）和 TDF（300mg）（EFV/FTC/TDF）。96 周时的主要疗效终点是 HIV-1 RNA 水平<50 拷贝/ml 的参与者比例（FDA 快照方法），预先设定的非劣效性边界为 10%，以支持 48 周的结果。主要安全性终点包括预先指定的神经精神不良事件和 96 周时空腹血脂的平均变化。

结果

在 734 名随机分配的参与者中，728 名接受了研究药物治疗，并纳入了分析。96 周时，DOR/3TC/TDF 组的 77.5%和 EFV/FTC/TDF 组的 73.6%的参与者达到了 HIV-1 RNA<50 拷贝/ml，治疗差异为 3.8%（95%置信区间，-2.4%至 10%）。病毒学失败率较低，且在各个治疗组之间相似，在 48 至 96 周之间没有观察到对 DOR 的额外耐药性。在 96 周时，与 EFV/FTC/TDF 组相比，DOR/3TC/TDF 组的神经精神不良事件和皮疹的发生率较低。在 96 周时，EFV/FTC/TDF 组的空腹低密度脂蛋白胆固醇和非高密度脂蛋白胆固醇（HDL-C）水平升高，但 DOR/3TC/TDF 组没有升高；总胆固醇/HDL-C 比值的平均变化相似。