Imperial College London, London, UK.
Kings College Hospital, London, UK.
Lancet HIV. 2018 Apr;5(4):e162-e171. doi: 10.1016/S2352-3018(18)30010-9. Epub 2018 Feb 20.
Abacavir and tenofovir alafenamide offer reduced bone toxicity compared with tenofovir disoproxil fumarate. We aimed to compare safety and efficacy of tenofovir alafenamide plus emtricitabine with that of abacavir plus lamivudine.
In this randomised, double-blind, active-controlled, non-inferiority phase 3 trial, HIV-1-positive adults (≥18 years) were screened at 79 sites in 11 countries in North America and Europe. Eligible participants were virologically suppressed (HIV-1 RNA <50 copies per mL) and on a stable three-drug regimen containing abacavir plus lamivudine. Participants were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to switch to fixed-dose tablets of tenofovir alafenamide (10 mg or 25 mg) plus emtricitabine (200 mg) or remain on abacavir (600 mg) plus lamivudine (300 mg), with matching placebo, while continuing to take the third drug. Randomisation was stratified by the third drug (boosted protease inhibitor vs other drug) at screening. Investigators, participants, and study staff giving treatment, assessing outcomes, and collecting data were masked to treatment group. The primary endpoint was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 48 (assessed by snapshot algorithm), with a 10% non-inferiority margin. We analysed the primary endpoint in participants enrolled before May 23, 2016 (when target sample size was reached), and we analysed safety in all enrolled participants who received at least one dose of study drug (including patients enrolled after these dates). This study was registered with ClinicalTrials.gov, number NCT02469246.
Study enrolment began on June 29, 2015, and the cutoff enrolment date for the week 48 primary endpoint analysis was May 23, 2016. 501 participants were randomly assigned and treated. At week 48, virological suppression was maintained in 227 (90%) of 253 participants receiving tenofovir alafenamide plus emtricitabine compared with 230 (93%) of 248 receiving abacavir plus lamivudine (difference -3·0%, 95% CI -8·2 to 2·0), showing non-inferiority. Few participants discontinued treatment because of adverse events: 12 (4%) of 280 participants in the tenofovir alafenimide plus emtricitabine group and nine (3%) of 276 in the abacavir plus lamivudine group. Three participants had serious, treatment-related adverse events: one each with renal colic and neutropenia in the tenofovir alafenamide plus emtricitabine group, and one myocardial infarction in the abacavir plus lamivudine group. There were no treatment-related deaths.
Tenofovir alafenamide, in combination with emtricitabine and various third drugs, maintained high efficacy with a renal and bone safety profile similar to that of abacavir. In virologically suppressed patients, a regimen containing tenofovir alafenamide could be an alternative to those containing abacavir, without concern for new onset of renal or bone toxicities or hyperlipidaemia.
Gilead Sciences Inc.
与富马酸替诺福韦二吡呋酯相比，阿巴卡韦和替诺福韦艾拉酚胺可降低骨毒性。我们旨在比较替诺福韦艾拉酚胺加恩曲他滨与阿巴卡韦加拉米夫定的安全性和疗效。
在这项随机、双盲、活性对照、非劣效性 3 期试验中，在北美和欧洲 11 个国家的 79 个地点筛选了 HIV-1 阳性成人（≥18 岁）。合格的参与者在病毒学上受到抑制（HIV-1 RNA<50 拷贝/mL），并正在服用稳定的三药方案，其中包含阿巴卡韦加拉米夫定。参与者按计算机生成的分配序列（块大小为 4）随机分配（1:1），转换为替诺福韦艾拉酚胺（10 mg 或 25 mg）加恩曲他滨（200 mg）的固定剂量片剂，或继续服用阿巴卡韦（600 mg）加拉米夫定（300 mg），并使用匹配的安慰剂，同时继续服用第三种药物。在筛选时，根据第三种药物（增效蛋白酶抑制剂与其他药物）对随机分组进行分层。研究人员、参与者和给予治疗、评估结果和收集数据的研究人员对治疗组进行了盲法。主要终点是在第 48 周时（通过快照算法评估）病毒学抑制的参与者比例，具有 10%的非劣效性边界。我们在 2016 年 5 月 23 日（达到目标样本量）之前入组的参与者中分析了主要终点，我们在接受至少一剂研究药物的所有入组参与者（包括在这些日期之后入组的患者）中分析了安全性。这项研究在 ClinicalTrials.gov 上注册，编号为 NCT02469246。
研究于 2015 年 6 月 29 日开始入组，第 48 周主要终点分析的截止入组日期为 2016 年 5 月 23 日。501 名参与者被随机分配并接受治疗。在第 48 周时，与接受阿巴卡韦加拉米夫定的 248 名参与者中的 230 名（93%）相比，接受替诺福韦艾拉酚胺加恩曲他滨的 253 名参与者中有 227 名（90%）保持病毒学抑制（差异-3.0%，95%CI-8.2 至 2.0），显示非劣效性。因不良事件而停药的参与者很少：替诺福韦艾拉酚胺加恩曲他滨组有 12 名（4%）和阿巴卡韦加拉米夫定组有 9 名（3%）。有 3 名参与者发生了与治疗相关的严重不良事件：替诺福韦艾拉酚胺加恩曲他滨组各有 1 例出现肾绞痛和中性粒细胞减少症，阿巴卡韦加拉米夫定组有 1 例发生心肌梗死。没有与治疗相关的死亡。
替诺福韦艾拉酚胺联合恩曲他滨和各种第三种药物，保持了高效的疗效，且具有与阿巴卡韦相似的肾脏和骨骼安全性特征。在病毒学受到抑制的患者中，含有替诺福韦艾拉酚胺的方案可以替代含有阿巴卡韦的方案，而不必担心新出现的肾脏或骨骼毒性或血脂异常。
吉利德科学公司。
