Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom.
Clin Infect Dis. 2015 Jun 1;60 Suppl 3:S170-6. doi: 10.1093/cid/civ092.
The choice of preferred regimens for human immunodeficiency virus postexposure prophylaxis (PEP) has evolved over the last 2 decades as more data have become available regarding the safety and tolerability of newer antiretroviral drugs. We undertook a systematic review to assess the safety and efficacy of antiretroviral options for PEP to inform the World Health Organization guideline revision process.
Four databases were searched up to 1 June 2014 for studies reporting outcomes associated with specific PEP regimens. Data on PEP completion and discontinuation due to adverse events was extracted and pooled estimates were obtained using random-effects meta-analyses.
Fifteen studies (1830 PEP initiations) provided evaluable information on 2-drug regimens (zidovudine [ZDV]- or tenofovir [TDF]-based regimens), and 10 studies (1755 initiations) provided evaluable information on the third drug, which was usually a protease inhibitor. The overall quality of the evidence was rated as very low. For the 2-drug regimen, PEP completion rates were 78.4% (95% confidence interval [CI], 66.1%-90.7%) for people receiving a TDF-based regimen and 58.8% (95% CI, 47.2%-70.4%) for a ZDV-based regimen; the rate of PEP discontinuation due to an adverse event was lower among people taking TDF-based PEP (0.3%; 95% CI, 0%-1.1%) vs a ZDV-based regimen (3.2%; 95% CI, 1.5%-4.9%). For the 3-drug comparison, PEP completion rates were highest for the TDF-based regimens (TDF+emtricitabine [FTC]+lopinavir/ritonavir [LPV/r], 71.1%; 95% CI, 43.6%-98.6%; TDF+FTC+raltegravir [RAL], 74.7%; 95% CI, 41.4%-100%; TDF+FTC+ boosted darunavir [DRV/r], 93.9%; 95% CI, 90.2%-97.7%) and lowest for ZDV+ lamivudine [3TC]+LPV/r (59.1%; 95% CI, 36.2%-82.0%). Discontinuations due to adverse drug reactions were lowest for TDF+FTC+RAL (1.9%; 95% CI, 0%-3.8%) and highest for ZDV+3TC+boosted atazanavir (21.2%; 95% CI, 13.5%-30.0%).
The findings of this review provide evidence supporting the use of coformulated TDF and 3TC/FTC as preferred backbone drugs for PEP. Choice of third drug will depend on setting; for resource-limited settings, LPV/r is a reasonable choice, pending the improved availability of better-tolerated drugs with less potential for drug-drug interactions.
随着更多有关新型抗逆转录病毒药物的安全性和耐受性的数据出现，人类免疫缺陷病毒暴露后预防（PEP）首选方案的选择在过去 20 年中发生了变化。我们进行了一项系统评价，以评估用于 PEP 的抗逆转录病毒药物的安全性和疗效，为世界卫生组织指南修订过程提供信息。
截至 2014 年 6 月 1 日，我们对四个数据库进行了检索，以查找与特定 PEP 方案相关的结局的研究报告。提取有关 PEP 完成和因不良事件而停药的数据，并使用随机效应荟萃分析获得汇总估计值。
15 项研究（1830 例 PEP 启动）提供了关于 2 种药物方案（齐多夫定[ZDV]-或替诺福韦[TDF]-为基础的方案）的可评估信息，10 项研究（1755 例启动）提供了关于第三种药物的可评估信息，该药物通常为蛋白酶抑制剂。证据的总体质量被评为非常低。对于 2 种药物方案，接受 TDF 为基础方案的 PEP 完成率为 78.4%（95%置信区间[CI]，66.1%-90.7%），接受 ZDV 为基础方案的 PEP 完成率为 58.8%（95% CI，47.2%-70.4%）；接受 TDF 为基础 PEP 的患者因不良反应停药的比例较低（0.3%；95% CI，0%-1.1%），而 ZDV 为基础方案为 3.2%（95% CI，1.5%-4.9%）。对于 3 种药物比较，TDF 为基础方案的 PEP 完成率最高（TDF+恩曲他滨[FTC]+洛匹那韦/利托那韦[LPV/r]，71.1%；95% CI，43.6%-98.6%；TDF+FTC+拉替拉韦[RAL]，74.7%；95% CI，41.4%-100%；TDF+FTC+达芦那韦[DRV/r]，93.9%；95% CI，90.2%-97.7%），ZDV+拉米夫定[3TC]+LPV/r 最低（59.1%；95% CI，36.2%-82.0%）。因药物不良反应停药的比例最低的是 TDF+FTC+RAL（1.9%；95% CI，0%-3.8%），最高的是 ZDV+3TC+阿扎那韦（21.2%；95% CI，13.5%-30.0%）。
本综述的结果为使用共配方 TDF 和 3TC/FTC 作为 PEP 的首选骨干药物提供了证据支持。第三药物的选择将取决于具体情况；在资源有限的情况下，LPV/r 是一种合理的选择，等待更好耐受且潜在药物相互作用较少的药物的可用性改善。
