Background

Optimal strategies for pre-exposure prophylaxis (PrEP) engagement in generalised HIV epidemics are unknown. We aimed to assess PrEP uptake and engagement after population-level HIV testing and universal PrEP access to characterise gaps in the PrEP cascade in rural Kenya and Uganda.

Methods

We did a 72-week interim analysis of observational data from the ongoing SEARCH (Sustainable East Africa Research in Community Health) study. Following community sensitisation and PrEP education, we did HIV testing and offered PrEP at health fairs and facilities in 16 rural communities in western Kenya, eastern Uganda, and western Uganda. We provided enhanced PrEP counselling to individuals 15 years and older who were assessed as having an elevated HIV risk on the basis of serodifferent partnership or empirical risk score, or who otherwise self-identified as being at high risk but were not in serodifferent partnerships or identified by the risk score. PrEP follow-up visits were done at facilities, homes, or community locations. We assessed PrEP uptake within 90 days of HIV testing, programme engagement (follow-up visit attendance at week 4, week 12, and every 12 weeks thereafter), refills, self-reported adherence up to 72 weeks, and concentrations of tenofovir in hair samples from individuals reporting HIV risk and adherence during follow-up, and analysed factors associated with uptake and adherence. This study is registered with ClinicalTrials.gov, NCT01864603.

Findings

Between June 6, 2016, and June 23, 2017, 70 379 community residents 15 years or older who had not previously been diagnosed with HIV were tested during population-level HIV testing. Of these individuals, 69 121 tested HIV-negative, 12 935 of whom had elevated HIV risk (1353 [10%] serodifferent partnership, 6938 [54%] risk score, 4644 [36%] otherwise self-identified risk). 3489 (27%) initiated PrEP, 2865 (82%) of whom did so on the same day as HIV testing and 1733 (50%) of whom were men. PrEP uptake was lower among individuals aged 15–24 years (adjusted odds ratio 0·55, 95% CI 0·45–0·68) and mobile individuals (0·61, 0·41–0·91). At week 4, among 3466 individuals who initiated PrEP and did not withdraw or die before the first visit, 2215 (64%) were engaged in the programme, 1701 (49%) received medication refills, and 1388 (40%) self-reported adherence. At week 72, 1832 (56%) of 3274 were engaged, 1070 (33%) received a refill, and 900 (27%) self-reported adherence. Among participants reporting HIV risk at weeks 4–72, refills (89–93%) and self-reported adherence (70–76%) were high. Among sampled participants self-reporting adherence at week 24, the proportion with tenofovir concentrations in the hair reflecting at least four doses taken per week was 66%, and reflecting seven doses per week was 44%. Participants who stopped PrEP accepted HIV testing at 4274 (83%) of 5140 subsequent visits; half of these participants later restarted PrEP. 29 participants of 3489 who initiated PrEP had serious adverse events, including seven deaths. Five adverse events (all grade 3) were assessed as being possibly related to the study drug.

Interpretation

During population-level HIV testing, inclusive risk assessment (combining serodifferent partnership, an empirical risk score, and self-identification of HIV risk) was feasible and identified individuals who could benefit from PrEP. The biggest gap in the PrEP cascade was PrEP uptake, particularly for young and mobile individuals. Participants who initiated PrEP and had perceived HIV risk during follow-up reported taking PrEP, but one-third had drug concentrations consistent with poor adherence, highlighting the need for novel approaches and long-acting formulations as PrEP roll-out expands.

Funding

National Institutes of Health, President's Emergency Plan for AIDS Relief, Bill & Melinda Gates Foundation, and Gilead Sciences

中文翻译：

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肯尼亚和乌干达农村地区人口艾滋病毒检测后提供的暴露前预防的接受、参与和坚持：对 SEARCH 研究观察数据的 72 周中期分析。

背景

在普遍的 HIV 流行中暴露前预防 (PrEP) 的最佳策略尚不清楚。我们的目的是在人群水平的艾滋病毒检测和普遍的 PrEP 获取之后评估 PrEP 的采用和参与，以了解肯尼亚和乌干达农村地区 PrEP 级联中的差距。

方法

我们对正在进行的 SEARCH（东非社区健康可持续研究）研究的观察数据进行了为期 72 周的中期分析。在社区宣传和 PrEP 教育之后，我们在肯尼亚西部、乌干达东部和乌干达西部的 16 个农村社区的健康博览会和设施中进行了 HIV 检测并提供 PrEP。我们为 15 岁及以上的个人提供了强化的 PrEP 咨询，这些人根据血清不同的伙伴关系或经验风险评分被评估为具有较高的 HIV 风险，或者自我认定为高风险但没有血清不同的伙伴关系或已确定的个人通过风险评分。PrEP 后续访视在设施、家庭或社区地点进行。我们评估了 HIV 检测后 90 天内的 PrEP 吸收情况、计划参与情况（第 4 周、第 12 周以及此后每 12 周的随访出勤率）、补充量、长达 72 周的自我报告依从性以及头发中替诺福韦的浓度随访期间报告艾滋病毒风险和依从性的个人样本，并分析了与吸收和依从性相关的因素。本研究已在 ClinicalTrials.gov 注册，NCT01864603。

发现

2016年6月6日至2017年6月23日期间，70 379名15岁及以上以前未诊断出感染艾滋病毒的社区居民在人口一级艾滋病毒检测期间接受了检测。在这些人中，69 121 人检测结果为 HIV 阴性，其中 12 935 人的 HIV 风险较高（1353 人 [10%] 存在血清差异性伴侣关系，6938 人 [54%] 风险评分，4644 人 [36%] 自行确定的风险）。3489 人（27%）开始了 PrEP，其中 2865 人（82%）在 HIV 检测的同一天进行了 PrEP，其中 1733 人（50%）是男性。15-24 岁个体（调整后比值比 0·55，95% CI 0·45–0·68）和流动个体（0·61，0·41–0·91）的 PrEP 摄取率较低。在第 4 周，在 3466 名开始 PrEP 并且在第一次就诊前没有退出或死亡的人中，2215 人 (64%) 参与了该计划，1701 人 (49%) 接受了药物补充，1388 人 (40%) 自我报告坚持。在第 72 周，3274 人中有 1832 人（56%）参与了活动，1070 人（33%）接受了补充，900 人（27%）自我报告遵守。在第 4-72 周报告 HIV 风险的参与者中，补充 (89-93%) 和自我报告的依从性 (70-76%) 较高。在第 24 周自我报告依从性的样本参与者中，头发中替诺福韦浓度反映每周至少服用四剂的比例为 66%，反映每周服用七剂的比例为 44%。停止 PrEP 的参与者在 5140 次后续就诊中，有 4274 人（83%）接受了 HIV 检测；这些参与者中有一半后来重新启动了 PrEP。3489 名启动 PrEP 的参与者中，有 29 人出现严重不良事件，其中 7 人死亡。五个不良事件（均为 3 级）被评估为可能与研究药物相关。

解释

在人群水平的艾滋病毒检测期间，包容性风险评估（结合血清差异伙伴关系、经验风险评分和艾滋病毒风险的自我识别）是可行的，并确定了可以从 PrEP 中受益的个人。PrEP 级联中最大的差距是 PrEP 的吸收，特别是对于年轻人和流动人口。开始 PrEP 并在随访期间意识到 HIV 风险的参与者报告说服用了 PrEP，但三分之一的药物浓度与依从性差一致，这凸显了随着 PrEP 推广的扩大，需要新方法和长效制剂。

资金

美国国立卫生研究院、总统艾滋病救援紧急计划、比尔及梅琳达·盖茨基金会和吉利德科学公司