Adherence, adverse drug reactions, and discontinuation associated with adverse drug reactions of HIV post-exposure prophylaxis: a meta-analysis based on cohort studies

<b>Objective:</b> Evaluate the profiles of post-exposure prophylaxis (PEP) adherence, adverse drug reactions (ADRs), and discontinuation associated with ADRs to provide information for further PEP program improvement and increase adherence to PEP.<b>Methods:</b> The Web of Science, PubMed, Embase, and the Cochrane Library were searched for cohort studies reporting data related to PEP adherence or ADRs (PROSPERO, CRD42022385073). Pooled estimates of adherence, the incidence of ADRs and discontinuation associated with ADRs, and their 95% confidence intervals (CI) were calculated separately for the included literature using random effects models. For substantial heterogeneity, meta-regression and subgroup analyses were conducted to explore sources of heterogeneity.<b>Results:</b> Overall adherence was 58.4% (95% CI: 50.9%–65.8%), with subgroup analysis showing differences in adherence across samples, with the highest adherence among men who had sex with men (MSM) (72.4%, 95% CI: 63.4%–81.3%) and the lowest adherence among survivors of sexual assault (SAs) (41.7%, 95% CI: 28.0%–55.3%). The incidence of ADRs was 60.3% (95% CI: 50.3%-70.3%), and the prevalence of PEP discontinuation associated with ADRs was 32.7% (95% CI: 23.7%-41.7%), with subgroup analyses revealing disparities in the prevalence of discontinuation associated with ADRs among samples with different drug regimens. Time trend analysis showed a slight downward trend in the incidence of ADRs and PEP discontinuation associated with ADRs.<b>Conclusion:</b> Adherence to PEP was less than 60% across samples, however, there was significant heterogeneity depending on the samples. SAs had the lowest adherence and the highest incidence of PEP discontinuation. Ongoing adherence education for participants, timely monitoring, and management of ADRs may improve adherence. Although PEP has been implemented in most countries for over two decades, there is a notable absence of adherence evaluation and a need for systematic analysis regarding the impact of adverse drug reactions.We performed a meta-analysis to characterize PEP adherence in samples, assess adverse drug reactions during PEP treatment, and the possibility of PEP discontinuation associated with adverse drug reactions.Adherence to PEP was less than 60% across samples, however, there was significant heterogeneity depending on the samples. Particularly, survivors of sexual assault have the lowest adherence and the highest incidence of PEP discontinuation.Adherence, adverse drug reactions, and discontinuation associated with adverse drug reactions of HIV post-exposure prophylaxis: A Meta-analysis based on cohort studies Although PEP has been implemented in most countries for over two decades, there is a notable absence of adherence evaluation and a need for systematic analysis regarding the impact of adverse drug reactions. We performed a meta-analysis to characterize PEP adherence in samples, assess adverse drug reactions during PEP treatment, and the possibility of PEP discontinuation associated with adverse drug reactions. Adherence to PEP was less than 60% across samples, however, there was significant heterogeneity depending on the samples. Particularly, survivors of sexual assault have the lowest adherence and the highest incidence of PEP discontinuation. Adherence, adverse drug reactions, and discontinuation associated with adverse drug reactions of HIV post-exposure prophylaxis: A Meta-analysis based on cohort studies

### 研究标题：人类免疫缺陷病毒（HIV）暴露后预防（PEP）的依从性、药物不良反应（ADRs）及与药物不良反应相关的停药情况：基于队列研究的荟萃分析

<b>研究目的：</b> 评估暴露后预防（PEP）的依从性、药物不良反应（ADRs）及与药物不良反应相关的停药情况，为进一步优化暴露后预防方案、提升其依从性提供参考依据。

<b>研究方法：</b> 检索Web of Science、PubMed、Embase及考克兰图书馆（Cochrane Library）中报道与暴露后预防依从性或药物不良反应相关数据的队列研究（PROSPERO注册号：CRD42022385073）。采用随机效应模型对纳入文献分别计算依从率、药物不良反应发生率、与药物不良反应相关的停药率及其95%置信区间（CI）。针对存在显著异质性的结果，采用Meta回归与亚组分析探究异质性来源。

<b>研究结果：</b> 整体样本的暴露后预防依从率为58.4%（95%CI：50.9%~65.8%）；亚组分析显示不同人群样本的依从率存在差异，男男性行为者（MSM）依从率最高，达72.4%（95%CI：63.4%~81.3%），性侵犯幸存者（SAs）依从率最低，为41.7%（95%CI：28.0%~55.3%）。药物不良反应发生率为60.3%（95%CI：50.3%~70.3%），与药物不良反应相关的暴露后预防停药率为32.7%（95%CI：23.7%~41.7%）；亚组分析显示，不同用药方案人群的与药物不良反应相关的停药率存在差异。时间趋势分析显示，药物不良反应发生率及与药物不良反应相关的暴露后预防停药率均呈轻微下降趋势。

<b>研究结论：</b> 整体样本的暴露后预防依从率不足60%，但不同人群样本间存在显著异质性。性侵犯幸存者的依从率最低，且暴露后预防停药率最高。对受试者开展持续的依从性教育、及时监测与处理药物不良反应，或可提升暴露后预防依从性。尽管多数国家已实施暴露后预防方案二十余年，但目前仍显著缺乏针对依从性的评估体系，且亟需开展关于药物不良反应影响的系统性分析。本研究通过荟萃分析明确了不同样本队列的暴露后预防依从性特征，评估了暴露后预防治疗期间的药物不良反应情况，以及与药物不良反应相关的暴露后预防停药可能性。