Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial
Post-exposure prophylaxis with doxycycline to prevent sexually transmitted infections in men who have sex with men: an open-label randomised substudy of the ANRS IPERGAY trial
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DOI：
10.1016/s1473-3099(17)30725-9
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发表时间：
2018-03-01
影响因子：
56.3
通讯作者：
Meyer, Laurence
中科院分区：
文献类型：
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作者：
Molina, Jean-Michel;Charreau, Isabelle;Meyer, Laurence
据报道，在男男性行为者中，性传播感染（STIs）的发病率增加。我们的目的是评估是否暴露后预防（PEP）与强力霉素可以减少发病率的STIs.Methods所有参与者参加他们的预定访问在开放标签扩展的ANRS IPERGAY试验在法国（18岁或18岁以上与男性发生无安全套性行为并使用富马酸替诺福韦酯+恩曲他滨进行HIV暴露前预防的男性）有资格入选本开放式研究，标签随机化研究。受试者在中心随机分配（1：1），在性生活后24小时内或无预防性治疗后单次口服200 mg多西环素PEP。主要终点是在10个月随访期间首次发生STI（淋病、衣原体或梅毒）。采用Kaplan-Meier方法估计各组主要终点发生的累积概率，并与对数秩检验进行比较。对意向治疗人群（包括所有随机化受试者）进行主要疗效分析。所有参与者都接受了降低风险的咨询和避孕套，并定期接受艾滋病毒检测。该试验注册于ClinicalTrials.gov，编号为NCT 01473472。结果在2015年7月20日至2016年1月21日期间，我们随机分配了232名参与者（强力霉素PEP组n=116，无PEP组n= 116），随访时间中位数为8.7个月（IQR 7.8-9.7）。PEP组的参与者每月使用680 mg多西环素（IQR 280-1450）。73名参与者在随访期间出现新的STI，PEP组28名（9个月概率22%，95% CI 15-32），无PEP组45名（42%，33-53;对数秩检验p=0.007）。服用PEP的参与者首次STI的发生率低于未服用PEP的参与者（风险比[HR] 0.53; 95% CI 0.33-0.85; p=0.008）。衣原体（HR 0.30; 95% CI 0.13-0.70; p=0.006）和梅毒（0.27; 0.07-0.98; p=0.047）首次发作的发生率观察到相似的结果;淋病首次发作的结果无显著差异（HR 0.83; 0.47-1.47; p=0.52）。没有观察到艾滋病毒血清转换，所有102例性传播感染中有72例（71%）无症状。两个研究组的严重不良事件发生率相似。PEP组62例（53%）参与者和无PEP组47例（41%）参与者报告了胃肠道不良事件（p=0.05）。多西环素PEP可降低高危男性同性性行为者首次细菌性STI发作的发生率。
Background Increased rates of sexually transmitted infections (STIs) have been reported among men who have sex with men. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of STIs.Methods All participants attending their scheduled visit in the open-label extension of the ANRS IPERGAY trial in France (men aged 18 years or older having condomless sex with men and using pre-exposure prophylaxis for HIV with tenofovir disoproxil fumarate plus emtricitabine) were eligible for inclusion in this open-label randomised study. Participants were randomly assigned (1:1) at a central site to take a single oral dose of 200 mg doxycycline PEP within 24 h after sex or no prophylaxis. The primary endpoint was the occurrence of a first STI (gonorrhoea, chlamydia, or syphilis) during the 10-month follow-up. The cumulative probability of occurrence of the primary endpoint was estimated in each group with the Kaplan-Meier method and compared with the log-rank test. The primary efficacy analysis was done on the intention-to-treat population, comprising all randomised participants. All participants received risk-reduction counselling and condoms, and were tested regularly for HIV. This trial is registered with ClinicalTrials.gov number, NCT01473472.Findings Between July 20, 2015, and Jan 21, 2016, we randomly assigned 232 participants (n=116 in the doxycycline PEP group and n=116 in the no-PEP group) who were followed up for a median of 8.7 months (IQR 7.8-9.7). Participants in the PEP group used a median of 680 mg doxycycline per month (IQR 280-1450). 73 participants presented with a new STI during follow-up, 28 in the PEP group (9-month probability 22%, 95% CI 15-32) and 45 in the no-PEP group (42%, 33-53; log-rank test p=0.007). The occurrence of a first STI in participants taking PEP was lower than in those not taking PEP (hazard ratio [HR] 0.53; 95% CI 0.33-0.85; p=0.008). Similar results were observed for the occurrence of a first episode of chlamydia (HR 0.30; 95% CI 0.13-0.70; p=0.006) and of syphilis (0.27; 0.07-0.98; p=0.047); for a first episode of gonorrhoea the results did not differ significantly (HR 0.83; 0.47-1.47; p=0.52). No HIV seroconversion was observed, and 72 (71%) of all 102 STIs were asymptomatic. Rates of serious adverse events were similar in the two study groups. Gastrointestinal adverse events were reported in 62 (53%) participants in the PEP group and 47 (41%) in the no-PEP group (p=0.05).Interpretation Doxycycline PEP reduced the occurrence of a first episode of bacterial STI in high-risk men who have sex with men.