口服暴露前预防（PrEP）预防 HIV：对所有人群的临床效果、安全性、依从性和风险补偿的系统评价和荟萃分析。
Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations.
机构信息
Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin 7, Ireland
Centre for Health Policy and Management, Trinity College Dublin, Dublin 2, Ireland.
出版信息
BMJ Open. 2022 May 11;12(5):e048478. doi: 10.1136/bmjopen-2020-048478.
OBJECTIVE
To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to prevent HIV.
METHODS
Databases (PubMed, Embase and the Cochrane Register of Controlled Trials) were searched up to 5 July 2020. Search terms for 'HIV' were combined with terms for 'PrEP' or 'tenofovir/emtricitabine'. RCTs were included that compared oral tenofovir-containing PrEP to placebo, no treatment or alternative medication/dosing schedule. The primary outcome was the rate ratio (RR) of HIV infection using a modified intention-to-treat analysis. Secondary outcomes included safety, adherence and risk compensation. All analyses were stratified a priori by population: men who have sex with men (MSM), serodiscordant couples, heterosexuals and people who inject drugs (PWIDs). The quality of individual studies was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was assessed using GRADE.
RESULTS
Of 2803 unique records, 15 RCTs met our inclusion criteria. Over 25 000 participants were included, encompassing 38 289 person-years of follow-up data. PrEP was found to be effective in MSM (RR 0.25, 95% CI 0.1 to 0.61; absolute rate difference (RD) -0.03, 95% CI -0.01 to -0.05), serodiscordant couples (RR 0.25, 95% CI 0.14 to 0.46; RD -0.01, 95% CI -0.01 to -0.02) and PWID (RR 0.51, 95% CI 0.29 to 0.92; RD -0.00, 95% CI -0.00 to -0.01), but not in heterosexuals (RR 0.77, 95% CI 0.46 to 1.29). Efficacy was strongly associated with adherence (p<0.01). PrEP was found to be safe, but unrecognised HIV at enrolment increased the risk of viral drug resistance mutations. Evidence for behaviour change or an increase in sexually transmitted infections was not found.
CONCLUSIONS
PrEP is safe and effective in MSM, serodiscordant couples and PWIDs. Additional research is needed prior to recommending PrEP in heterosexuals. No RCTs reported effectiveness or safety data for other high-risk groups, such as transgender women and sex workers.
PROSPERO REGISTRATION NUMBER
CRD42017065937.
目的
系统评价和荟萃分析随机对照试验（RCTs）中口服暴露前预防（PrEP）预防 HIV 的有效性和安全性。
方法
截至 2020 年 7 月 5 日，检索数据库（PubMed、Embase 和 Cochrane 对照试验登记处）。使用“HIV”的检索词与“PrEP”或“替诺福韦/恩曲他滨”的检索词相结合。纳入了比较口服含替诺福韦的 PrEP 与安慰剂、无治疗或替代药物/剂量方案的 RCTs。主要结局为使用修改后的意向治疗分析的 HIV 感染率比（RR）。次要结局包括安全性、依从性和风险补偿。所有分析均根据人群预先分层：男男性行为者（MSM）、性伴侣不一致的夫妇、异性恋者和注射毒品者（PWIDs）。使用 Cochrane 偏倚风险工具评估单个研究的质量，使用 GRADE 评估证据的确定性。
结果
在 2803 条独特的记录中，有 15 项 RCT 符合我们的纳入标准。超过 25000 名参与者被纳入，随访数据为 38289 人年。在 MSM（RR 0.25，95%CI 0.1 至 0.61；绝对差异率（RD）-0.03，95%CI-0.01 至-0.05）、性伴侣不一致的夫妇（RR 0.25，95%CI 0.14 至 0.46；RD-0.01，95%CI-0.01 至-0.02）和 PWIDs（RR 0.51，95%CI 0.29 至 0.92；RD-0.00，95%CI-0.00 至-0.01）中，PrEP 被证明是有效的，但在异性恋者中（RR 0.77，95%CI 0.46 至 1.29）则不然。疗效与依从性密切相关（p<0.01）。PrEP 是安全的，但在入组时未发现的 HIV 会增加病毒耐药突变的风险。没有发现行为改变或性传播感染增加的证据。
结论
在 MSM、性伴侣不一致的夫妇和 PWIDs 中，PrEP 是安全且有效的。在推荐异性恋者使用 PrEP 之前，需要进行更多的研究。没有 RCT 报告其他高危人群（如跨性别女性和性工作者）的有效性或安全性数据。
PROSPERO 注册号：CRD42017065937。
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