University of North Carolina School of Medicine, Chapel Hill, NC, USA.
Queen Mary University, London, UK.
Antiviral Res. 2019 Oct;170:104543. doi: 10.1016/j.antiviral.2019.104543. Epub 2019 Jul 4.
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.
达芦那韦/考比司他/恩曲他滨/替诺福韦艾拉酚胺（D/C/F/TAF）800/150/200/10mg 在 EMERALD 研究中进行了 96 周的研究（NCT02269917）。先前有非达芦那韦病毒学失败（VF）的病毒学抑制、有治疗经验的 HIV-1 阳性成人（允许）被随机分为（2:1）接受 D/C/F/TAF 或增效蛋白酶抑制剂（PI）加恩曲他滨/替诺福韦富马酸酯（F/TDF）治疗 48 周。在第 52 周时，PI 增效组的参与者被提供转换为 D/C/F/TAF（晚期转换，44 周 D/C/F/TAF 暴露）。所有参与者均接受 D/C/F/TAF 治疗直至第 96 周。疗效终点是累积协议定义的病毒学反弹（PDVR；确认病毒载量[VL]≥50 拷贝/mL）和 VL<50 拷贝/mL（病毒学抑制）和≥50 拷贝/mL（VF）（FDA 快照分析）。在 1141 名随机患者中，有 1080 名继续进入扩展阶段。少数患者发生 PDVR（D/C/F/TAF：3.1%，763 例患者累积至第 96 周；晚期转换：2.3%，352 例患者第 52-96 周）。第 96 周的病毒学抑制率为 90.7%（692/763）（D/C/F/TAF）和 93.8%（330/352）（晚期转换）。VF 分别为 1.2%和 1.7%。未观察到基线后达芦那韦、主要 PI、替诺福韦或恩曲他滨耐药相关突变。没有患者因疗效相关原因停药。少数患者因不良事件停药（D/C/F/TAF 组 2%）。在 D/C/F/TAF 组中维持了改善的肾功能和骨参数，并在晚期转换组中观察到，总胆固醇/高密度脂蛋白胆固醇比值略有增加。该研究的局限性是第 96 周分析中缺乏对照组。经过 96 周，D/C/F/TAF 导致 PDVR 率低、病毒学抑制率高、VF 少，且无耐药性发展。晚期转换结果与 D/C/F/TAF 第 48 周的结果一致。EMERALD 第 96 周的结果证实了 D/C/F/TAF 的疗效、对耐药性的高遗传屏障和安全性益处。
