Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study
Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: an observational cohort study
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DOI：
10.1016/s2352-3018(17)30089-9
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发表时间：
2017-09-01
期刊：
影响因子：
16.1
通讯作者：
Meyer, Laurence
中科院分区：
文献类型：
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作者：
Molina, Jean-Michel;Charreau, Isabelle;Meyer, Laurence
背景 按需暴露前预防 (PrEP) 的数据很少。我们实施了一项队列研究来评估其有效性、安全性和对性行为的影响。方法我们邀请之前在七个地点（六个在法国，一个在加拿大）参加随机安慰剂对照 ANRS IPERGAY 试验的男男性行为者和跨性别女性参与开放标签扩展，按需服用富马酸替诺福韦二吡呋酯（300 毫克）和恩曲他滨（200 毫克），在性交前后服用。我们评估了 HIV 和其他性传播感染 (STI) 的发病率、PrEP 依从性、安全性和性行为。统计分析包括 ANRS IPERGAY 试验随机阶段与开放标签阶段之间比例和发生率的比较，所有参与者均纳入安全性分析。 ANRS IPERGAY 已在临床试验中注册。 gov，编号 NCT01473472。调查结果 2014 年 11 月 4 日至 2015 年 1 月 27 日期间，我们招募了 361 名参与者。中位随访时间为 18.4 个月（IQR 17.7-19.1）。一名停止 PrEP 的参与者感染了 HIV。 HIV 发病率为每 100 人年 0.19 例（95% CI 0.01-1.08），而随机研究安慰剂组的 HIV 发病率为每 100 人年 6.60 例（3.60-11.05），表明按需 PrEP 的 HIV 发病率相对降低了 97%（95% CI 81-100）。参与者平均每月使用 18 粒研究药物 (IQR 11-25)，在 6 个月的访视中，336 名参与者中有 240 名 (71%) 在血浆中检测到替诺福韦。 49 名参与者 (14%) 报告了与药物相关的胃肠道事件，但具有自限性。只有四名参与者 (1%) 停止了 PrEP，其中三名是因为血浆肌酐升高。在 18 个月的随访中，报告上次接受肛交时发生无安全套性行为的参与者比例从基线时的 77%（176 名参与者中的 136 名）显着增加到 86%（77 名参与者中的 66 名）（趋势 p = 0.0004）。与随机阶段相比，在此开放标签阶段首次细菌性 STI 的发生率没有显着变化（分别为每 100 人年 59.0 例和 49.1 例；p= 0.11）。 解释 按需口服 PrEP 对于预防男男性行为的高危男性中的 HIV 感染非常有效，因此是每日 PrEP 的替代方案，扩大了 HIV 预防的选择。安全套使用率低导致的性传播感染高发生率并没有损害 PrEP 的功效，但需要经常进行检测。
Background Data for on-demand pre-exposure prophylaxis (PrEP) are scarce. We implemented a cohort study to assess its efficacy, safety, and effect on sexual behaviour.Methods We invited men and transgender women who have sex with men, previously enrolled in the randomised placebo-controlled ANRS IPERGAY trial at seven sites (six in France and one in Canada), to participate in an openlabel extension with on-demand tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg) to be taken before and after sexual intercourse. We assessed the incidence of HIV and other sexually transmitted infections (STIs), PrEP adherence, safety, and sexual behaviour. Statistical analyses included comparisons of proportions and incidence between the randomised phase of the ANRS IPERGAY trial and the open-label phase, and all participants were included in safety analyses. ANRS IPERGAY is registered with ClinicalTrials. gov, number NCT01473472.Findings Between Nov 4, 2014, and Jan 27, 2015, we enrolled 361 participants. Median follow-up was 18.4 months (IQR 17.7-19.1). One participant who discontinued PrEP acquired HIV infection. HIV incidence was 0.19 per 100 person-years (95% CI 0.01-1.08), compared with 6.60 per 100 person-years (3.60-11.05) in the placebo group of the randomised study, indicating a relative reduction of 97% (95% CI 81-100) in the incidence of HIV with ondemand PrEP. Participants used a median of 18 pills of study drugs per month (IQR 11-25), and at the 6 month visit 240 (71%) of 336 participants had tenofovir detected in plasma. Drug-related gastrointestinal events were reported in 49 participants (14%) but were self-limited. Only four participants (1%) discontinued PrEP, three because of an increase in plasma creatinine. The proportion of participants reporting condomless sex at their last receptive anal intercourse significantly increased from 77% (136 of 176 participants) at baseline to 86% (66 of 77 participants) at 18 months' follow-up (p for trend= 0.0004). The incidence of a first bacterial STI during this open-label phase did not change significantly compared with the randomised phase (59.0 vs 49.1 per 100 person-years, respectively; p= 0.11).Interpretation On-demand oral PrEP is highly effective at preventing HIV infection among high-risk men who have sex with men and therefore represents an alternative to daily PrEP, expanding choices for HIV prevention. High rates of STIs resulting from low condom use did not undermine PrEP efficacy, but warrant frequent testing.