Joint Clinical Research Centre, Kampala, Uganda.
Georgia Department of Public Health, Coastal Health District, Chatham CARE Center, Savannah, GA.
J Acquir Immune Defic Syndr. 2019 Nov 1;82(3):321-328. doi: 10.1097/QAI.0000000000002137.
Bictegravir, coformulated with emtricitabine/tenofovir alafenamide as a fixed-dose combination (B/F/TAF), is recommended for treatment of HIV-1-infection. Multiple studies of B/F/TAF in treatment-naive and virologically suppressed cohorts have shown high efficacy and tolerability with no treatment-emergent resistance through 48 weeks. Participants in these studies have been predominantly men. We report 48-week results from a phase 3 study evaluating switching to B/F/TAF, specifically in a globally distributed trial population of women.
In this multicenter, randomized, open-label, active-controlled, noninferiority trial (ClinicalTrials.gov NCT02652624), women living with HIV who were virologically suppressed (HIV-1 RNA levels <50 copies/mL) on a regimen containing either TAF or tenofovir disoproxil fumarate were randomly assigned (1:1) to switch to B/F/TAF (50/200/25 mg) or stay on baseline regimen (SBR) once daily for 48 weeks. Primary endpoint was proportion of participants with plasma HIV-1 RNA ≥50 copies/mL at week 48 (U.S. Food and Drug Administration snapshot algorithm); prespecified noninferiority margin was 4%.
We randomized 472 participants and treated 470 (234 B/F/TAF, 236 SBR). Switching to B/F/TAF was noninferior to SBR for the primary outcome, as 1.7% (4/234) vs 1.7% (4/236) had HIV-1 RNA ≥50 copies/mL at week 48 (difference 0.0%, 95.001% confidence interval: -2.9% to 2.9%). No individual receiving B/F/TAF developed treatment-emergent resistance. Both treatments were well-tolerated; no participant discontinued treatment because of an adverse event.
Fixed-dose combination B/F/TAF provides a safe and efficacious option for ongoing treatment of HIV in women. This study contributes important data on safety, tolerability, and outcomes of antiretroviral therapy among women living with HIV.
比克替拉韦、恩曲他滨和丙酚替诺福韦艾拉酚胺固定剂量复方（B/F/TAF）被推荐用于治疗 HIV-1 感染。多项在初治和病毒学抑制人群中开展的 B/F/TAF 研究均显示，在 48 周治疗期间，该药物具有较高的疗效和耐受性，且无治疗后出现的耐药性。这些研究的参与者主要为男性。我们报告了一项 3 期研究的 48 周结果，该研究评估了在全球分布的女性试验人群中转换为 B/F/TAF 的情况。
这是一项多中心、随机、开放标签、活性对照、非劣效性试验（ClinicalTrials.gov NCT02652624），在该试验中，正在接受包含替诺福韦艾拉酚胺或富马酸替诺福韦二吡呋酯的治疗方案、病毒学抑制（HIV-1 RNA 水平<50 拷贝/mL）的 HIV 感染者，随机（1:1）转换为服用 B/F/TAF（50/200/25 mg）或继续使用基线方案（SBR）每日一次，治疗 48 周。主要终点为第 48 周时血浆 HIV-1 RNA≥50 拷贝/mL 的参与者比例（美国食品和药物管理局快照算法）；预设的非劣效性边界为 4%。
我们随机分配了 472 名参与者，治疗了 470 名参与者（234 名服用 B/F/TAF，236 名服用 SBR）。转换为 B/F/TAF 与 SBR 相比，主要结局非劣效，第 48 周时，HIV-1 RNA≥50 拷贝/mL 的患者比例分别为 1.7%（4/234）和 1.7%（4/236）（差异 0.0%，95.001%置信区间：-2.9%至 2.9%）。没有接受 B/F/TAF 治疗的患者出现治疗后出现的耐药性。两种治疗均具有良好的耐受性；没有参与者因不良事件而停止治疗。
固定剂量复方 B/F/TAF 为女性 HIV 患者的持续治疗提供了一种安全有效的选择。这项研究提供了关于女性 HIV 感染者抗逆转录病毒治疗的安全性、耐受性和结局的重要数据。
