Background

There are few data available regarding the use of on-demand pre-exposure prophylaxis (PrEP) for HIV prevention. We aimed to assess PrEP effectiveness, adherence, and safety in adults using daily or on-demand PrEP.

Methods

We conducted a prospective observational cohort study (ANRS PREVENIR) at 26 sites in the Paris region, France. We enrolled HIV-negative adults (aged ≥18 years) at high risk of HIV infection who were starting or continuing PrEP. PrEP was prescribed as a fixed-dose combination of tenofovir disoproxil and emtricitabine (245 mg and 200 mg, respectively, per pill). PrEP could be prescribed as a daily regimen with one pill per day or, in men who have sex with men (MSM) or in transgender women who have sex with men, as an on-demand regimen following the IPERGAY dosing recommendation. At enrolment and every 3 months thereafter, participants were tested for HIV and provided information regarding the PrEP dosing regimen used. Adherence to PrEP was assessed by self-report and by tenofovir diphosphate concentrations in dried blood spots. The primary outcome of HIV-1 incidence was assessed using Poisson regression among participants who started PrEP. This study is registered with ClinicalTrials.gov, NCT03113123, and EudraCT, 2016A0157744.

Findings

Between May 3, 2017, and May 2, 2019, 3082 people were assessed for eligibility and 3065 participants were enrolled. 3056 (99·7%) of 3065 participants reported using PrEP and were included in the analyses. The median age was 36 years (IQR 29–43), 1344 (44·0%) of 3056 participants were PrEP-naive, and 3016 (98·7%) were MSM. At enrolment, 1540 (50·5%) of 3049 participants opted for daily PrEP dosing and 1509 (49·5%) opted for on-demand PrEP dosing; these proportions remained stable during follow-up. Median follow-up was 22·1 months (IQR 15·9–29·7) and incidence of study discontinuation was 17·6 participants (95% CI 16·5–18·7) per 100 person-years. At the data cutoff on Sept 30, 2020, there had been six HIV-1 seroconversions (three participants using daily PrEP and three using on-demand PrEP; all were MSM) over 5623 person-years. Overall HIV-1 incidence was 1·1 cases (95% CI 0·4–2·3) per 1000 person-years, and did not differ between participants using daily PrEP and those using on-demand PrEP (incidence rate ratio 1·00, 95% CI 0·13–7·49; p=0·99). Four participants (two using daily PrEP and two using on-demand PrEP) discontinued PrEP due to treatment-related adverse events (nausea [n=2], vomiting and diarrhoea [n=1], and lumbar pain [n=1]).

Interpretation

In this study, which enrolled mainly MSM, HIV-1 incidence on PrEP was low and did not differ between participants using daily PrEP and those using on-demand PrEP. On-demand PrEP therefore represents a valid alternative to daily PrEP for MSM, providing greater choice in HIV prevention.

Funding

ANRS/Maladies Infectieuses Emergentes, Gilead Sciences, SIDACTION, and Région Ile de France.

Translation

For the French translation of the abstract see Supplementary Materials section.

中文翻译：

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每日和按需使用恩曲他滨和替诺福韦地索普西 (ANRS PREVENIR) 进行 HIV 暴露前预防：一项前瞻性观察性队列研究

背景

关于使用按需暴露前预防 (PrEP) 预防 HIV 的可用数据很少。我们旨在评估成人使用每日或按需 PrEP 的 PrEP 有效性、依从性和安全性。

方法

我们在法国巴黎地区的 26 个地点进行了一项前瞻性观察性队列研究 (ANRS PREVENIR)。我们招募了正在开始或继续进行 PrEP 且处于 HIV 感染高风险的 HIV 阴性成人（年龄≥18 岁）。PrEP 被规定为替诺福韦酯和恩曲他滨的固定剂量组合（每片分别为 245 毫克和 200 毫克）。PrEP 可以作为每天服用一粒药丸的每日方案，或者在男男性行为者 (MSM) 或男男性行为者的跨性别女性中，按照 IPERGAY 剂量建议作为按需方案。在入组时和之后每 3 个月，参与者接受 HIV 检测，并提供有关使用的 PrEP 给药方案的信息。通过自我报告和干血斑中的替诺福韦二磷酸盐浓度评估对 PrEP 的依从性。在开始 PrEP 的参与者中使用泊松回归评估 HIV-1 发病率的主要结果。该研究已在 ClinicalTrials.gov、NCT03113123 和 EudraCT、2016A0157744 注册。

发现

在 2017 年 5 月 3 日至 2019 年 5 月 2 日期间，对 3082 人进行了资格评估，并招募了 3065 名参与者。3065 名参与者中有 3056 名 (99·7%) 报告使用了 PrEP 并被纳入分析。中位年龄为 36 岁（IQR 29-43），3056 名参与者中有 1344 名（44·0%）未接受 PrEP，3016 名（98·7%）为 MSM。在注册时，3049 名参与者中有 1540 名 (50·5%) 选择了每日 PrEP 给药，1509 名 (49·5%) 选择了按需 PrEP 给药；这些比例在随访期间保持稳定。中位随访时间为 22·1 个月（IQR 15·9-29·7），研究中止的发生率为每 100 人年 17·6 名参与者（95% CI 16·5-18·7）。在 2020 年 9 月 30 日的数据截止日期，超过 5623 人年发生了六次 HIV-1 血清转化（三名参与者使用每日 PrEP，三名使用按需 PrEP；均为 MSM）。总体 HIV-1 发病率为每 1000 人年 1·1 例 (95% CI 0·4-2·3)，并且在使用每日 PrEP 和使用按需 PrEP 的参与者之间没有差异（发病率比 1· 00, 95% CI 0·13–7·49；p=0·99)。四名参与者（两名使用每日 PrEP，两名使用按需 PrEP）由于治疗相关的不良事件（恶心 [n=2]、呕吐和腹泻 [n=1] 和腰痛 [n=1]）而停止了 PrEP .

解释

在这项主要招募 MSM 的研究中，PrEP 的 HIV-1 发病率很低，并且在使用每日 PrEP 的参与者和使用按需 PrEP 的参与者之间没有差异。因此，按需 PrEP 代表了 MSM 每日 PrEP 的有效替代方案，为 HIV 预防提供了更多选择。

资金

ANRS/Maladies Infectieuses Emergentes、Gilead Sciences、SIDACTION 和 Région Ile de France。

翻译

对于摘要的法语翻译，请参阅补充材料部分。