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在使用HIV暴露前预防药物的个体中,多西环素暴露后预防与细菌性性传播感染

Doxycycline Postexposure Prophylaxis and Bacterial Sexually Transmitted Infections Among Individuals Using HIV Preexposure Prophylaxis.

作者信息

Traeger Michael W, Leyden Wendy A, Volk Jonathan E, Silverberg Michael J, Horberg Michael A, Davis Teaniese L, Mayer Kenneth H, Krakower Douglas S, Young Jessica G, Jenness Samuel M, Marcus Julia L

机构信息

Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts.

Burnet Institute, Melbourne, Australia.

出版信息

JAMA Intern Med. 2025 Mar 1;185(3):273-281. doi: 10.1001/jamainternmed.2024.7186.

Abstract

IMPORTANCE

Doxycycline postexposure prophylaxis (doxyPEP) has been shown to decrease the incidence of bacterial sexually transmitted infections (STIs) among people assigned male sex at birth in clinical trials, but data from clinical practice are limited.

OBJECTIVE

To describe early uptake of doxyPEP and evaluate changes in STI incidence following doxyPEP initiation.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study of adults (aged ≥18 years) dispensed HIV preexposure prophylaxis (PrEP) at Kaiser Permanente Northern California during November 1, 2022, to December 31, 2023, examined electronic health record data to compare HIV PrEP users dispensed and not dispensed doxyPEP and rates of bacterial STIs before and after starting doxyPEP. Individuals were followed up from their first recorded STI test on or after November 1, 2020, until December 31, 2023, or discontinuation of health plan membership.

EXPOSURE

Pharmacy dispensing data were used to define doxyPEP recipients.

MAIN OUTCOMES AND MEASURES

Demographic and clinical characteristics were compared between individuals dispensed and not dispensed doxyPEP. Primary outcomes were incident chlamydia, gonorrhea, or infectious syphilis measured as quarterly STI positivity (proportion of individuals testing positive at least once per quarter). Among doxyPEP recipients, rate ratios (RRs) compared mean quarterly STI positivity from 24 months before to 12 months after starting doxyPEP. In an exploratory analysis, STI trends were evaluated for the full cohort, stratified by receipt of doxyPEP.

RESULTS

Among 11 551 HIV PrEP users (mean [SD] age, 39.9 [12.1] years; 95.1% male), 2253 (19.5%) were dispensed doxyPEP, of whom 2228 (98.9%) were male and 1096 (48.6%) had an STI in the year before starting doxyPEP. Compared with individuals not dispensed doxyPEP, doxyPEP recipients were older (mean [SD] age, 40.4 [10.8] vs 39.8 [12.4] years; P = .04) and had used HIV PrEP longer (mean [SD], 4.2 [2.8] vs 3.4 [2.6] years; P < .001), and a higher proportion were commercially insured (2091 [92.8%] vs 8270 [88.9%]; P < .001). Among doxyPEP recipients, quarterly chlamydia positivity decreased from 9.6% (95% CI, 9.0%-10.3%) before starting doxyPEP to 2.0% (95% CI, 1.5%-2.6%) after starting doxyPEP (RR, 0.21; 95% CI, 0.16-0.27; P < .001), with significant declines for each anatomic site of infection. Quarterly gonorrhea positivity decreased from 10.2% (95% CI, 9.6%-10.9%) before starting doxyPEP to 9.0% (95% CI, 8.0%-10.1%) after starting doxyPEP (RR, 0.88; 95% CI, 0.77-1.00; P = .048); site-specific declines were significant for rectal (RR, 0.81; 95% CI, 0.67-0.97; P = .02) and urethral (RR, 0.56; 95% CI, 0.40-0.79; P = .001) gonorrhea, but not pharyngeal gonorrhea. Quarterly syphilis positivity decreased from 1.7% (95% CI, 1.4%-1.9%) before starting doxyPEP to 0.3% (95% CI, 0.2%-0.6%) after starting doxyPEP (RR, 0.20; 95% CI, 0.11-0.37; P < .001). Positivity for STIs remained stable in individuals not dispensed doxyPEP.

CONCLUSIONS AND RELEVANCE

This study found that receipt of doxyPEP was associated with substantial declines in chlamydia and syphilis incidence and modest declines in urethral and rectal gonorrhea incidence among individuals using HIV PrEP. These findings suggest that doxyPEP may offer substantial benefits for reducing population-level STI transmission with broader implementation.

摘要

重要性

在临床试验中,多西环素暴露后预防(doxyPEP)已被证明可降低出生时被指定为男性的人群中细菌性性传播感染(STIs)的发病率,但临床实践数据有限。

目的

描述doxyPEP的早期使用情况,并评估开始使用doxyPEP后STIs发病率的变化。

设计、背景和参与者:这项回顾性队列研究对2022年11月1日至2023年12月31日期间在北加利福尼亚凯撒医疗中心接受HIV暴露前预防(PrEP)的成年人(年龄≥18岁)进行,研究通过检查电子健康记录数据,比较接受和未接受doxyPEP的HIV PrEP使用者以及开始使用doxyPEP前后细菌性STIs的发生率。个体从2020年11月1日或之后的首次记录的STI检测开始随访,直至2023年12月31日或终止健康计划会员资格。

暴露

药房配药数据用于定义doxyPEP接受者。

主要结局和指标

比较接受和未接受doxyPEP的个体的人口统计学和临床特征。主要结局是衣原体、淋病或感染性梅毒的发病率,以季度STI阳性率(每季度至少检测出一次阳性的个体比例)衡量。在doxyPEP接受者中,率比(RRs)比较了开始使用doxyPEP前24个月至开始后12个月的平均季度STI阳性率。在一项探索性分析中,对整个队列按是否接受doxyPEP进行分层,评估STIs趋势。

结果

在11551名HIV PrEP使用者中(平均[标准差]年龄为39.9[12.1]岁;95.1%为男性),2253人(19.5%)接受了doxyPEP,其中2228人(98.9%)为男性,1096人(48.6%)在开始使用doxyPEP前一年患有STI。与未接受doxyPEP的个体相比,doxyPEP接受者年龄更大(平均[标准差]年龄为40.4[10.8]岁对39.8[12.4]岁;P = 0.04),使用HIV PrEP的时间更长(平均[标准差]为4.2[2.8]年对3.4[2.6]年;P < 0.001),且商业保险覆盖比例更高(2091人[92.8%]对8270人[88.9%];P < 0.001)。在doxyPEP接受者中,衣原体季度阳性率从开始使用doxyPEP前的9.6%(95%CI,9.0%-10.3%)降至开始使用后2.0%(95%CI,1.5%-2.6%)(RR,0.21;95%CI,0.16-0.27;P < 0.001),每个感染解剖部位均有显著下降。淋病季度阳性率从开始使用doxyPEP前的10.2%(95%CI,9.6%-10.9%)降至开始使用后9.0%(95%CI,8.0%-10.1%)(RR,0.88;95%CI,0.77-1.00;P = 0.048);直肠(RR,0.81;95%CI,0.67-0.97;P = 0.02)和尿道(RR,0.56;95%CI,0.40-0.79;P = 0.001)淋病的部位特异性下降显著,但咽部淋病无显著下降。梅毒季度阳性率从开始使用doxyPEP前的1.7%(95%CI,1.4%-1.9%)降至开始使用后0.3%(95%CI,0.2%-0.6%)(RR,0.20;95%CI,0.11-0.37;P < 0.001)。未接受doxyPEP的个体中STIs阳性率保持稳定。

结论和意义

本研究发现,接受doxyPEP与使用HIV PrEP的个体中衣原体和梅毒发病率大幅下降以及尿道和直肠淋病发病率适度下降相关。这些发现表明,更广泛地实施doxyPEP可能为减少人群层面的STI传播带来显著益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8866/11877173/20b9703cb2a6/jamainternmed-e247186-g001.jpg

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