Background

In DISCOVER, a multinational, randomised controlled trial, emtricitabine and tenofovir alafenamide compared with emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and renal safety biomarkers at week 48. We report outcomes analysed after all participants had completed 96 weeks of follow-up.

Methods

This study is an ongoing, randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial done at 94 community, public health, and hospital-associated clinics located in Europe and North America. Adult cisgender men and transgender women who have sex with men, both with a high risk of acquiring HIV as determined by self-reported sexual behaviour or recent sexually transmitted infections, were randomly assigned (1:1) to receive either emtricitabine and tenofovir alafenamide (200/25 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir alafenamide group), or emtricitabine and tenofovir disoproxil fumarate (200/300 mg) tablets daily, with matched placebo tablets (emtricitabine and tenofovir disoproxil fumarate group). The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last participant had completed 96 weeks of follow-up. This trial is registered with ClinicalTrials.gov, number NCT02842086.

Findings

Between Sept 13, 2016, and June 30, 2017, 5387 participants were randomly assigned to receive emtricitabine and tenofovir alafenamide (n=2694) or emtricitabine and tenofovir disoproxil fumarate (n=2693), contributing 10 081 person-years of follow-up. At 96 weeks of follow-up, there were eight HIV infections in participants who had received emtricitabine and tenofovir alafenamide (0·16 infections per 100 person-years [95% CI 0·07–0·31]) and 15 in participants who had received emtricitabine and tenofovir disoproxil fumarate (0·30 infections per 100 person-years [0·17–0·49]). Emtricitabine and tenofovir alafenamide maintained its non-inferiority to emtricitabine and tenofovir disoproxil fumarate for HIV prevention (IRR 0·54 [95% CI 0·23–1·26]). Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits. Rates of sexually transmitted infections remained high and similar across groups (21 cases per 100 person-years for rectal gonorrhoea and 28 cases per 100 person-years for rectal chlamydia). Emtricitabine and tenofovir alafenamide continued to show superiority over emtricitabine and tenofovir disoproxil fumarate in all but one of the six prespecified bone mineral density and renal biomarkers. There was more weight gain among participants who had received emtricitabine and tenofovir alafenamide (median weight gain 1·7 kg vs 0·5 kg, p<0·0001).

Interpretation

Emtricitabine and tenofovir alafenamide is safe and effective for longer-term pre-exposure prophylaxis in cisgender men and transgender women who have sex with men.

Funding

Gilead Sciences.

中文翻译：

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恩曲他滨和替诺福韦艾拉酚胺与恩曲他滨和富马酸替诺福韦二吡呋酯用于 HIV-1 暴露前预防的长期安全性和有效性：随机、双盲、安慰剂对照、3 期试验的第 96 周结果

背景

在 DISCOVER 一项跨国随机对照试验中，恩曲他滨和替诺福韦艾拉酚胺与恩曲他滨和富马酸替诺福韦二吡呋酯相比，在第 48 周显示出非劣效性预防 HIV 以及改善骨矿物质密度和肾脏安全生物标志物。完成了 96 周的随访。

方法

这项研究是一项正在进行的、随机、双盲、多中心、主动对照、3 期、非劣效性试验，在位于欧洲和北美的 94 个社区、公共卫生和医院相关诊所进行。根据自我报告的性行为或最近的性传播感染确定，成年顺性别男性和与男性发生性关系的跨性别女性均具有感染 HIV 的高风险，他们被随机分配（1:1）接受恩曲他滨和替诺福韦艾拉酚胺（每日 200/25 毫克）片，搭配匹配的安慰剂片（恩曲他滨和替诺福韦艾拉酚胺组），或每天服用恩曲他滨和富马酸替诺福韦酯（200/300 毫克）片，搭配匹配的安慰剂片（恩曲他滨和富马酸替诺福韦酯组）。主要疗效结果是艾滋病毒感染事件。当最后一名参与者完成 96 周的随访时，评估了每 100 人年的 HIV-1 感染率。该试验已在 ClinicalTrials.gov 注册，编号 NCT02842086。

发现

2016 年 9 月 13 日至 2017 年 6 月 30 日期间，5387 名参与者被随机分配接受恩曲他滨和替诺福韦艾拉酚胺 (n=2694) 或恩曲他滨和富马酸替诺福韦酯 (n=2693)，对 10081 人进行了随访. 在 96 周的随访中，接受恩曲他滨和替诺福韦艾拉酚胺治疗的参与者中有 8 例 HIV 感染（每 100 人年 0·16 例感染 [95% CI 0·07–0·31]），15 例接受曾接受恩曲他滨和富马酸替诺福韦酯（每 100 人年 0·30 次感染 [0·17–0·49]）。恩曲他滨和替诺福韦艾拉酚胺在预防 HIV 方面保持其非劣效于恩曲他滨和富马酸替诺福韦酯 (IRR 0·54 [95% CI 0·23–1·26])。大约 78-82% 的参与者报告在所有研究访问中服用研究药物的时间超过 95%。各组的性传播感染率仍然很高且相似（直肠淋病为每 100 人年 21 例，直肠衣原体为每 100 人年 28 例）。恩曲他滨和替诺福韦艾拉酚胺在除六种预先指定的骨矿物质密度和肾脏生物标志物之一外的所有其他方面继续表现出优于恩曲他滨和富马酸替诺福韦二吡呋酯的优势。接受恩曲他滨和替诺福韦艾拉酚胺的参与者体重增加更多（中位体重增加 1·7 公斤 恩曲他滨和替诺福韦艾拉酚胺在除六种预先指定的骨矿物质密度和肾脏生物标志物之一外的所有其他方面继续表现出优于恩曲他滨和富马酸替诺福韦二吡呋酯的优势。接受恩曲他滨和替诺福韦艾拉酚胺的参与者体重增加更多（中位体重增加 1·7 公斤 恩曲他滨和替诺福韦艾拉酚胺在除六种预先指定的骨矿物质密度和肾脏生物标志物之一外的所有其他方面继续表现出优于恩曲他滨和富马酸替诺福韦二吡呋酯的优势。接受恩曲他滨和替诺福韦艾拉酚胺的参与者体重增加更多（中位体重增加 1·7 公斤与0·5 公斤相比，p<0·0001)。

解释

恩曲他滨和替诺福韦艾拉酚胺对于顺性别男性和男男性行为跨性别女性的长期暴露前预防是安全有效的。

资金

吉利德科学。