Orlando Immunology Center, Orlando, FL, USA.
Midway Immunology and Research Center, Fort Pierce, FL, USA.
Lancet HIV. 2017 May;4(5):e205-e213. doi: 10.1016/S2352-3018(17)30032-2. Epub 2017 Mar 2.
Tenofovir alafenamide is a prodrug that reduces tenofovir plasma concentrations by 90% compared with tenofovir disoproxil fumarate, thereby decreasing bone and renal risks. The coformulation of rilpivirine, emtricitabine, and tenofovir alafenamide has recently been approved, and we aimed to investigate the efficacy, safety, and tolerability of switching to this regimen compared with remaining on coformulated efavirenz, emtricitabine, and tenofovir disoproxil fumarate.
In this randomised, double-blind, placebo-controlled, non-inferiority trial, HIV-1-infected adults were enrolled at 120 hospitals and outpatient clinics in eight countries in North America and Europe. Participants were virally suppressed (HIV-1 RNA <50 copies per mL) on efavirenz, emtricitabine, and tenofovir disoproxil fumarate for at least 6 months before enrolment and had creatinine clearance of at least 50 mL/min. Participants were randomly assigned (1:1) to receive a single-tablet regimen of rilpivirine (25 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) or to continue a single-tablet regimen of efavirenz (600 mg), emtricitabine (200 mg), and tenofovir disoproxil fumarate (300 mg), with matching placebo. Investigators, participants, study staff, and those assessing outcomes were masked to treatment group. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of less than 50 copies per mL at week 48 (assessed by the US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of 8%. This study was registered with ClinicalTrials.gov, number NCT02345226.
Between Jan 26, 2015, and Aug 27, 2015, 875 participants were randomly assigned and treated (438 with rilpivirine, emtricitabine, and tenofovir alafenamide and 437 with efavirenz, emtricitabine, tenofovir disoproxil fumarate). Viral suppression at week 48 was maintained in 394 (90%) of 438 participants assigned to the tenofovir alafenamide regimen and 402 (92%) of 437 assigned to the tenofovir disoproxil fumarate regimen (difference -2·0%, 95·001% CI -5·9 to 1·8), demonstrating non-inferiority. 56 (13%) of 438 in participants in the rilpivirine, emtricitabine, and tenofovir alafenamide group experienced treatment-related adverse events compared with 45 (10%) of 437 in the efavirenz, emtricitabine, and tenofovir disoproxil fumarate group.
Switching to rilpivirine, emtricitabine, and tenofovir alafenamide from efavirenz, emtricitabine, and tenofovir disoproxil fumarate was non-inferior in maintaining viral suppression and was well tolerated at 48 weeks. These findings support guidelines recommending tenofovir alafenamide-based regimens, including coformulation with rilpivirine and emtricitabine, as initial and ongoing treatment for HIV-1 infection.
Gilead Sciences.
替诺福韦艾拉酚胺是一种前体药物，与富马酸替诺福韦二吡呋酯相比，可将替诺福韦的血浆浓度降低 90%，从而降低骨和肾脏风险。利匹韦林、恩曲他滨和替诺福韦艾拉酚胺的复方制剂最近已获得批准，我们旨在研究与继续使用富马酸替诺福韦二吡呋酯、恩曲他滨和替诺福韦艾拉酚胺相比，改用该方案的疗效、安全性和耐受性。
在这项随机、双盲、安慰剂对照、非劣效性试验中，在北美和欧洲的 8 个国家的 120 家医院和门诊诊所招募了 HIV-1 感染的成年人。参与者在入组前至少接受了 6 个月的依非韦伦、恩曲他滨和富马酸替诺福韦二吡呋酯治疗，病毒载量得到抑制（HIV-1 RNA<50 拷贝/ml），且肌酐清除率至少为 50 ml/min。参与者被随机分配（1:1）接受利匹韦林（25 mg）、恩曲他滨（200 mg）和替诺福韦艾拉酚胺（25 mg）的单一片剂方案或继续使用依非韦伦（600 mg）、恩曲他滨（200 mg）和富马酸替诺福韦二吡呋酯（300 mg）的单一片剂方案，同时匹配安慰剂。研究人员、参与者、研究人员和评估结果的人员对治疗组均进行了盲法处理。主要终点是在第 48 周时血浆 HIV-1 RNA<50 拷贝/ml 的参与者比例（通过美国食品和药物管理局快照算法评估），预先指定的非劣效性边界为 8%。该研究在 ClinicalTrials.gov 注册，编号为 NCT02345226。
2015 年 1 月 26 日至 2015 年 8 月 27 日期间，共有 875 名参与者被随机分配并接受治疗（利匹韦林、恩曲他滨和替诺福韦艾拉酚胺组 438 名，依非韦伦、恩曲他滨和替诺福韦二吡呋酯组 437 名）。在第 48 周时，438 名接受替诺福韦艾拉酚胺方案治疗的参与者中有 394 名（90%）和 437 名接受替诺福韦二吡呋酯方案治疗的参与者中有 402 名（92%）病毒载量得到抑制（差异-2.0%，95.001%CI-5.9 至 1.8），表明非劣效性。与接受依非韦伦、恩曲他滨和替诺福韦二吡呋酯治疗的参与者相比，接受利匹韦林、恩曲他滨和替诺福韦艾拉酚胺治疗的参与者中有 56 名（13%）发生了与治疗相关的不良事件，而接受依非韦伦、恩曲他滨和替诺福韦二吡呋酯治疗的参与者中有 45 名（10%）。
与继续使用依非韦伦、恩曲他滨和替诺福韦二吡呋酯相比，改用利匹韦林、恩曲他滨和替诺福韦艾拉酚胺在维持病毒抑制方面非劣效，且在 48 周时耐受性良好。这些发现支持了指南，建议使用替诺福韦艾拉酚胺为基础的方案，包括与利匹韦林和恩曲他滨联合使用，作为 HIV-1 感染的初始和持续治疗。
吉利德科学公司。
