Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Orlando Immunology Center, Orlando, FL, USA.
Lancet HIV. 2018 Jul;5(7):e347-e356. doi: 10.1016/S2352-3018(18)30091-2. Epub 2018 Jun 18.
Switching from therapy based on a boosted protease inhibitor to bictegravir, emtricitabine, and tenofovir alafenamide could avoid drug interactions and unwanted side-effects in virologically suppressed adults with HIV-1 infection, while maintaining a high barrier to resistance and providing a simplified once-daily, single-tablet regimen. Here, we report 48 week results of a phase 3 study investigating this switch.
In this multicentre, randomised, open-label, active-controlled, non-inferiority, phase 3 trial, adults with HIV-1 infection were enrolled at 121 outpatient centres in ten countries. Eligible participants were aged 18 years or older, had an estimated glomerular filtration rate of 50 mL per min or higher, had been virologically suppressed (plasma HIV-1 RNA <50 copies per mL) for 6 months or more before screening, and were on a regimen consisting of boosted atazanavir or darunavir plus either emtricitabine and tenofovir disoproxil fumarate or abacavir and lamivudine. We randomly assigned participants (1:1), using a computer-generated randomisation sequence, to switch to co-formulated once-daily bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg), herein known as the bictegravir group, or to remain on their baseline boosted protease inhibitor regimen, herein known as the boosted protease inhibitor group, for 48 weeks. Randomisation was stratified by use of tenofovir disoproxil fumarate or abacavir at screening. The primary endpoint was the proportion of participants with plasma HIV-1 RNA of 50 copies per mL or higher at week 48 (by US Food and Drug Administration snapshot algorithm), with a prespecified non-inferiority margin of 4%. Efficacy and safety analyses included all participants who received at least one dose of study drug. This study is ongoing but not actively recruiting patients and is registered with ClinicalTrials.gov, number NCT02603107.
Between Dec 2, 2015, and July 15, 2016, 578 participants were randomly assigned and 577 were treated (290 in the bictegravir group and 287 in the boosted protease inhibitor group). At week 48, five participants (2%) in the bictegravir group and five (2%) in the boosted protease inhibitor group had plasma HIV-1 RNA of 50 copies per mL or higher (difference 0·0%, 95·002% CI -2·5 to 2·5), thus switching to the bictegravir regimen was non-inferior to continued boosted protease inhibitor therapy. The overall incidence and severity of adverse events was similar between groups, although headache occurred more frequently in the bictegravir group than in the boosted protease inhibitor group. 233 (80%) participants in the bictegravir group and 226 (79%) in the boosted protease inhibitor group had an adverse event. Only two (1%) participants in the bictegravir group and one (<1%) in the boosted protease inhibitor group discontinued treatment because of adverse events. 54 participants (19%) in the bictegravir group had drug-related adverse events compared with six (2%) in the protease inhibitor group.
Fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide might be a safe and efficacious alternative to continued boosted protease inhibitor therapy in adults with HIV-1 infection.
Gilead Sciences.
对于已接受基于增效蛋白酶抑制剂的治疗且病毒学抑制的 HIV-1 感染者，转换为比克替拉韦、恩曲他滨和替诺福韦艾拉酚胺，可避免药物相互作用和不良反应，同时保持高耐药屏障，并提供简化的每日一次单片方案。在此，我们报告了一项 3 期研究的 48 周结果，该研究旨在探索这种转换。
这是一项多中心、随机、开放标签、活性对照、非劣效性 3 期临床试验，在 10 个国家的 121 个门诊中心招募了 HIV-1 感染的成年人。合格的参与者年龄在 18 岁或以上，估计肾小球滤过率为 50 mL/min 或以上，在筛选前已经接受了 6 个月或以上的增效蛋白酶抑制剂方案治疗且病毒学抑制（血浆 HIV-1 RNA<50 拷贝/mL），且正在接受包含增效阿扎那韦或达芦那韦加恩曲他滨和替诺福韦二吡呋酯或阿巴卡韦和拉米夫定的方案治疗。我们使用计算机生成的随机序列，以 1:1 的比例将参与者随机分配（双盲）至转换为每日一次的固定剂量比克替拉韦（50 mg）、恩曲他滨（200 mg）和替诺福韦艾拉酚胺（25 mg），即比克替拉韦组，或继续使用其基线增效蛋白酶抑制剂方案，即增效蛋白酶抑制剂组，治疗 48 周。随机分组按筛选时使用替诺福韦二吡呋酯或阿巴卡韦进行分层。主要终点是第 48 周时血浆 HIV-1 RNA<50 拷贝/mL 的参与者比例（根据美国食品和药物管理局的快照算法），非劣效性边界为 4%。疗效和安全性分析包括接受至少一剂研究药物的所有参与者。本研究正在进行中，但不再招募患者，在 ClinicalTrials.gov 注册，编号为 NCT02603107。
2015 年 12 月 2 日至 2016 年 7 月 15 日期间，随机分配了 578 名参与者，577 名参与者接受了治疗（比克替拉韦组 290 名，增效蛋白酶抑制剂组 287 名）。第 48 周时，比克替拉韦组有 5 名（2%）参与者和增效蛋白酶抑制剂组有 5 名（2%）参与者的血浆 HIV-1 RNA 为 50 拷贝/mL 或更高（差异 0·0%，95·002%CI-2·5 至 2·5），因此，转换为比克替拉韦方案与继续增效蛋白酶抑制剂治疗相比非劣效。两组间不良反应的总发生率和严重程度相似，尽管比克替拉韦组头痛的发生率高于增效蛋白酶抑制剂组。比克替拉韦组有 233 名（80%）参与者和增效蛋白酶抑制剂组有 226 名（79%）参与者发生了不良反应。只有 2 名（1%）比克替拉韦组和 1 名（<1%）增效蛋白酶抑制剂组的参与者因不良反应而停止治疗。比克替拉韦组有 54 名（19%）参与者发生了药物相关不良反应，而蛋白酶抑制剂组有 6 名（2%）参与者发生了药物相关不良反应。
固定剂量比克替拉韦、恩曲他滨和替诺福韦艾拉酚胺可能是 HIV-1 感染者继续增效蛋白酶抑制剂治疗的一种安全有效的替代方案。
吉利德科学公司。
