Background Doravirine (DOR), a novel non-nucleoside reverse-transcriptase inhibitor (NNRTI), is active against wild-type Human Immunodeficiency Virus (HIV)-1 and the most common NNRTI-resistant variants, and has a favorable and unique in vitro resistance profile. Methods DRIVE-AHEAD is a phase 3, double-blind, non-inferiority trial. Antiretroviral treatment-naive adults with ≥1000 HIV-1 RNA copies/mL were randomized (1:1) to once-daily, fixed-dose DOR at 100 mg, lamivudine at 300 mg, and tenofovir disoproxil fumarate (TDF) at 300 mg (DOR/3TC/TDF) or to efavirenz at 600 mg, emtricitabine at 200 mg, and TDF at 300 mg (EFV/FTC/TDF) for 96 weeks. The primary efficacy endpoint was the proportion of participants with <50 HIV-1 RNA copies/mL at week 48 (Food and Drug Administration snapshot approach; non-inferiority margin 10%). Results Of the 734 participants randomized, 728 were treated (364 per group) and included in the analyses. At week 48, 84.3% (307/364) of DOR/3TC/TDF recipients and 80.8% (294/364) of EFV/FTC/TDF recipients achieved <50 HIV-1 RNA copies/mL (difference 3.5%, 95% CI, -2.0, 9.0). DOR/3TC/TDF recipients had significantly lower rates of dizziness (8.8% vs 37.1%), sleep disorders/disturbances (12.1% vs 25.2%), and altered sensorium (4.4% vs 8.2%) than EFV/FTC/TDF recipients. Mean changes in fasting low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) were significantly different between DOR/3TC/TDF and EFV/FTC/TDF (-1.6 vs +8.7 mg/dL and -3.8 vs +13.3 mg/dL, respectively). Conclusions In HIV-1 treatment-naive adults, DOR/3TC/TDF demonstrated non-inferior efficacy to EFV/FTC/TDF at week 48 and was well tolerated, with significantly fewer neuropsychiatric events and minimal changes in LDL-C and non-HDL-C compared with EFV/FTC/TDF. Clinical Trials Registration NCT02403674.

中文翻译：

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在未接受过人类免疫缺陷病毒-1病毒治疗的未成年人中，Doravirine / Lamivudine /替诺福韦富马酸替尼福韦不逊于Efavirenz / Emtricitabine /替诺福韦富马酸替诺福韦：第48周DRIVE-AHEAD试验结果。

背景Doravirine（DOR）是一种新型的非核苷逆转录酶抑制剂（NNRTI），对野生型人免疫缺陷病毒（HIV）-1和最常见的NNRTI抗性变异株具有活性，并且在体外具有良好而独特的作用电阻曲线。方法DRIVE-AHEAD是一项三阶段，双盲，非自卑性试验。初次接受抗逆转录病毒治疗且≥1000 HIV-1 RNA复制/ mL的成年人，随机分配（1：1）每日一次，固定剂量DOR 100 mg，拉米夫定300 mg和替诺福韦富马酸替诺福韦酯（TDF）300 mg （DOR / 3TC / TDF）或600 mg依非韦伦，200 mg恩曲他滨和300 mg TDF（EFV / FTC / TDF）治疗96周。主要功效终点是第48周时具有<50 HIV-1 RNA拷贝/ mL的受试者所占比例（食品和药物管理局快照法；非劣效性为10％）。结果在734名随机分组的参与者中，有728名接受了治疗（每组364名），并包括在分析中。在第48周时，DOR / 3TC / TDF受体的84.3％（307/364）和EFV / FTC / TDF受体的80.8％（294/364）的HIV-1 RNA拷贝/ mL <50（差异3.5％，95％） CI，-2.0、9.0）。与EFV / FTC / TDF接受者相比，DOR / 3TC / TDF接受者的头晕率（8.8％比37.1％），睡眠障碍/干扰（12.1％对25.2％）和感觉改变（4.4％vs 8.2％）明显更低。DOR / 3TC / TDF和EFV / FTC / TDF之间的空腹低密度脂蛋白胆固醇（LDL-C）和非高密度脂蛋白胆固醇（non-HDL-C）的平均变化显着不同（-1.6 vs +8.7 mg / dL和-3.8对+13.3 mg / dL）。结论在未接受HIV-1治疗的成年人中，与EFV / FTC / TDF相比，DOR / 3TC / TDF在第48周时表现出对EFV / FTC / TDF的非劣效且耐受性良好，神经精神病事件明显较少，LDL-C和非HDL-C的变化极小。临床试验注册NCT02403674。