Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial.
Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial.
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DOI：
10.1016/s2352-3018(17)30156-x
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发表时间：
2018-03
期刊：
影响因子：
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通讯作者：
HPTN 067 (ADAPT) study team
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文献类型：
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作者：
Bekker LG;Roux S;Sebastien E;Yola N;Amico KR;Hughes JP;Marzinke MA;Hendrix CW;Anderson PL;Elharrar V;Stirratt M;Rooney JF;Piwowar-Manning E;Eshleman SH;McKinstry L;Li M;Dye BJ;Grant RM;HPTN 067 (ADAPT) study team
女性中每日与非每日口服 HIV 暴露前预防 (PrEP) 的相对可行性和可接受性尚不清楚。我们的目的是研究非每日 PrEP 方案对成年女性的可行性。我们在南非开普敦的一个研究中心进行了一项随机、开放、2 期临床试验 (HPTN 067/ADAPT)，使用恩曲他滨加富马酸替诺福韦酯进行口服 PrEP。参与者是成年女性（年龄≥18岁），每周接受一次直接观察给药，持续 5 周，然后在第 6 周随机分配（1:1:1）至三种非盲性 PrEP 方案之一，在 24 周内自行给药：每日；时间驱动（每周两次加性交后剂量）；或事件驱动（性行为前和性行为后各服用一粒药片）。主要结局是 PrEP 覆盖率（性行为前 4 天内至少一剂，性行为后 24 小时内至少一剂）、为实现特定治疗方案的依从性和覆盖率所需或使用的药物，以及症状和副作用。所有分析均按意向治疗进行。该试验已在 ClinicalTrials.gov 注册，编号 NCT01327651；试验已完成，本报告提供最终分析。 2011年9月12日至2012年10月3日期间，有191名女性参加了该试验。 178 名受试者 (93%) 完成了直接观察给药，并被随机分配为自我给药阶段的三种 PrEP 方案之一：59 名受试者被分配每日方案，59 名受试者被分配时间驱动方案，60 名受试者被分配事件驱动方案。女性的中位年龄为 26 岁（IQR 21-37；范围 18-52）。在分配日常方案的女性中，PrEP 覆盖了 1952 起性事件中的 1459 起 (75%)，而分配给时间驱动方案的女性则覆盖了 1074 起性事件中的 599 起 (56%)（比值比 [OR] 2·35，95% CI 1·43–3·83；p=0·0007），而分配到时间驱动方案的女性则覆盖了 1542 起性事件中的 798 起 (52%)。分配的 事件驱动方案（2·76、1·68–4·53；p<0·0001）。分配非每日方案的女性完全依从所需的药片更少（与每日方案相比，时间驱动方案的相对平均值为 2·53 [95% CI 2·39–2·69]，事件驱动方案的相对平均值为 4·16 [3·59–4·82]；p<0·0001）。副作用并不常见。总共发生了 8 例 HIV 血清转化，其中 4 例记录在自我给药阶段（2 例采用时间驱动方案，2 例采用事件驱动方案）。分配日常方案的女性对分配方案的依从率为 75%（9652 剂中的 7283 剂），而分配时间驱动方案的妇女（3616 剂中的 2367 剂；p=0·0028）为 65%，分配事件驱动方案的妇女为 53%（2203 剂中的 1161 剂；p<0·0001）。当前一周报告性别时，分配每日方案的女性（107 个样本中的 73 [68%]）比分配时间驱动方案（72 个样本中的 42 [58%]）和事件驱动方案（99 个样本中的 41 [41%]）的女性更频繁地检测到 PrEP 药物（高于量化下限）。与时间驱动或事件驱动给药相比，每日 PrEP 给药可提高性事件的覆盖率、提高对治疗方案的依从性并提高药物浓度。这些发现支持女性每日使用 PrEP 联合口服恩曲他滨加富马酸替诺福韦二吡呋酯的建议。艾滋病毒预防试验网络。
The relative feasibility and acceptability of daily versus non-daily dosing of oral HIV pre-exposure prophylaxis (PrEP) among women are unknown. We aimed to investigate the feasibility of non-daily PrEP regimens in adult women. We did a randomised, open-label, phase 2 clinical trial (HPTN 067/ADAPT) of oral PrEP with emtricitabine plus tenofovir disoproxil fumarate at a research centre in Cape Town, South Africa. Participants were adult women (age ≥ 18 years) who received directly observed dosing once a week for 5 weeks followed by random assignment (1:1:1) at week 6 to one of three unblinded PrEP regimens for self-administered dosing over 24 weeks: daily; time-driven (twice a week plus a post-sex dose); or event-driven (one tablet both before and after sex). Primary outcomes were PrEP coverage (at least one dose within the 4 days before sex and one dose within 24 h after sex), pills needed or used to achieve regimen-specific adherence and coverage, and symptoms and side-effects. All analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01327651; the trial is completed and this report presents the final analysis. Between Sept 12, 2011, and Oct 3, 2012, 191 women were enrolled to the trial. 178 (93%) completed directly observed dosing and were randomly assigned one of the three PrEP regimens for the self-administered phase: 59 were allocated the daily regimen, 59 the time-driven regimen, and 60 the event-driven regimen. Median age of women was 26 years (IQR 21–37; range 18–52). In women allocated the daily regimen, 1459 (75%) of 1952 sex events were covered by PrEP, compared with 599 (56%) of 1074 sex events among those assigned the time-driven regimen (odds ratio [OR] 2·35, 95% CI 1·43–3·83; p=0·0007) and 798 (52%) of 1542 sex events among those allotted the event-driven regimen (2·76, 1·68–4·53; p<0·0001). Fewer pills were needed for complete adherence in women allocated non-daily regimens (vs daily regimen, relative mean 2·53 [95% CI 2·39–2·69] for the time-driven regimen and 4·16 [3·59–4·82] for the event-driven regimen; p<0·0001). Side-effects were uncommon. Eight HIV seroconversions occurred overall, with four documented during the self-administered phase (two with the time-driven regimen and two with the event-driven regimen). Adherence to the assigned regimen was 75% (7283 of 9652 doses taken) for women allocated the daily regimen compared with 65% for those assigned the time-driven regimen (2367 of 3616 doses taken; p=0·0028) and 53% for those allotted the event-driven regimen (1161 of 2203 doses taken; p<0·0001). When sex was reported in the previous week, PrEP drugs were detected (above the lower limits of quantification) more frequently in women assigned the daily regimen (73 [68%] of 107 samples) than in those allocated the time-driven regimen (42 [58%] of 72 samples) and the event-driven regimen (41 [41%] of 99 samples). Daily PrEP dosing resulted in higher coverage of sex events, increased adherence to the regimen, and augmented drug concentrations than did either time-driven or event-driven dosing. These findings support recommendations for daily use of PrEP with oral emtricitabine plus tenofovir disoproxil fumarate in women. HIV Prevention Trials Network.