On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial
On-demand pre-exposure prophylaxis with tenofovir disoproxil fumarate plus emtricitabine among men who have sex with men with less frequent sexual intercourse: a post-hoc analysis of the ANRS IPERGAY trial
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DOI：
10.1016/s2352-3018(19)30341-8
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发表时间：
2020-02-01
期刊：
影响因子：
16.1
通讯作者：
Rabian, C.
中科院分区：
文献类型：
--
作者：
Antoni, Guillemette;Tremblay, Cecile;Rabian, C.
ANRS IPERGAY发现，在与HIV高危男性发生性行为的男性中，口服富马酸替诺福韦二氧吡酯加恩曲他滨的按需暴露前预防（PrEP）与安慰剂相比，HIV-1发病率相对降低86%。我们的目的是调查按需PrEP是否对艾滋病毒风险较低的个体同样有效。方法ANRS IPERGAY试验的参与者被随机分配接受PrEP（每片300 mg富马酸替诺福韦二氧吡酯和200 mg恩曲他滨的固定剂量组合）或安慰剂。主要终点是HIV-1感染的诊断。通过计数每次随访时退回的药片和估计冷冻血浆样本中的替诺福韦浓度来评估药丸摄取情况。每次访问时对参与者进行访谈，以评估PrEP的使用模式。ANRS IPERGAY试验双盲期修改意向治疗人群的所有参与者均符合此事后分析的条件。我们计算了高PrEP依从性（每月系统服用15片或更少，或在性交期间经常服用）性交次数较少的随访时间。利用冷冻标本进行第四代HIV-1/2 ELISA检测、血浆HIV-1 RNA检测和western blot分析，估计HIV感染时间，并根据Fiebig分期确定HIV感染阶段。比较了两个治疗组中性生活频率较低且PrEP依从性高的个体的HIV发病率。ANRS IPERGAY试验已在ClinicalTrials.gov注册，注册号为NCT01473472。在2012年2月22日至2014年10月17日期间，400名随机分配接受PrEP （n=199）或安慰剂（n=201）的参与者被纳入该分析。270名参与者在研究期间至少有一段较不频繁的性交，并高度坚持PrEP，代表134人年的随访，占总研究随访的31%。在此期间，两组参与者每月的性交次数中位数为5.0次（IQR 2.0-10.0），每月服用的药物中位数为9.5粒（6.0-13.0）。安慰剂组诊断出6例HIV-1感染（HIV发病率为9.2 / 100人-年；95% CI 3.4-20.1），富马酸替诺福韦双氧proxil +恩曲他滨组无诊断（HIV发病率为0 / 100人-年；0-5.4;p=0.013）， HIV发病率相对降低100% （95% CI 39-100）。对于与性交频率较低的男性发生性关系的男性，可以选择每日或按需PrEP方案。Elsevier Ltd.版权所有版权所有。
Background ANRS IPERGAY found that on-demand pre-exposure prophylaxis (PrEP) with oral tenofovir disoproxil fumarate plus emtricitabine was associated with an 86% relative reduction of HIV-1 incidence compared with placebo among men who have sex with men at high risk of HIV. We aimed to investigate whether on-demand PrEP was similarly effective among individuals with lower exposure to HIV risk.Methods Participants in the ANRS IPERGAY trial were randomly assigned to receive PrEP (fixed-dose combination of 300 mg tenofovir disoproxil fumarate and 200 mg emtricitabine per pill) or placebo. The primary endpoint was the diagnosis of HIV-1 infection. Pill uptake was assessed by counting returned pills at each follow-up and by estimating tenofovir concentration from frozen plasma samples. Participants were interviewed at each visit to assess the pattern of PrEP use. All participants enrolled in the modified intention-to-treat population of the double-blind phase of the ANRS IPERGAY trial were eligible for this post-hoc analysis. We calculated the total follow-up time for periods of less frequent sexual intercourse with high PrEP adherence (15 pills or fewer per month taken systematically or often during sexual intercourse). To estimate the time of HIV acquisition, fourth-generation HIV-1/2 ELISA assays, plasma HIV-1 RNA assays, and western blot analyses were done with use of frozen samples, and the stage of HIV infection was defined according to Fiebig staging. HIV incidence was compared between the two treatment groups among individuals who had less frequent sexual intercourse with high PrEP adherence. The ANRS IPERGAY trial is registered with ClinicalTrials.gov, NCT01473472.Findings 400 participants who were randomly assigned to receive PrEP (n=199) or placebo (n=201) between Feb 22, 2012, and Oct 17, 2014, were included in this analysis. 270 participants had at least one period of less frequent sexual intercourse with high PrEP adherence during the study, representing 134 person-years of follow-up and 31% of the total study follow-up. During these periods, participants in both groups reported a median of 5.0 (IQR 2.0-10.0) episodes of sexual intercourse per month and used a median of 9.5 (6.0-13.0) pills per month. Six HIV-1 infections were diagnosed in the placebo group (HIV incidence of 9.2 per 100 person-years; 95% CI 3.4-20.1) and none were diagnosed in the tenofovir disoproxil fumarate plus emtricitabine arm (HIV incidence of 0 per 100 person-years; 0-5.4; p=0.013), with a relative reduction of HIV incidence of 100% (95% CI 39-100).Interpretation A choice between daily or on-demand PrEP regimens could be offered to men who have sex with men who have less frequent sexual intercourse. Copyright (C) 2019 Elsevier Ltd. All rights reserved.