美国华盛顿大学Connie Celum团队研究了恩曲他滨和富马酸替诺福韦二吡呋酯在顺性别妇女中的HIV暴露前预防作用。该研究于2024年3月1日发表在《美国医学会杂志》上。

恩曲他滨和富马酸替诺福韦二吡呋酯（F/TDF）用于HIV暴露前预防（PrEP）对于依从性高（>4剂/周）的男男性行为者（MSM）非常有效。在顺性别女性中，PrEP的真实世界有效性和F/TDF依从性尚未得到很好的描述。

为了探讨F/TDF治疗顺性别女性PrEP的有效性及其与依从性的关系，研究组使用来自2012年至2020年在6个国家进行的11项F/TDF PrEP批准后研究的数据，其中包括6296名15至69岁的顺性别女性。根据客观测量（干血斑中的替诺福韦二磷酸浓度或血浆中的替诺福韦浓度；n = 288）和主观测量（电子药丸帽监测、药丸计数、自我报告和研究报告的依从性量表；n = 2954）的依从性水平评估HIV发病率，使用基于组的轨迹建模。干预措施为每天口服一次F/TDF。根据依从性轨迹对HIV发病率进行亚组分析。主要结局为艾滋病发病率。

6296名参与者中，46%来自肯尼亚，28%来自南非，21%来自印度，2.9%来自乌干达，1.6%来自博茨瓦纳，0.8%来自美国。所有研究中PrEP启动时的平均（SD）年龄为25（7）岁，61%的参与者年龄小于25岁。总体艾滋病发病率为0.72/100人-年（6296名参与者中有32例HIV诊断）。共确定了四组不同的依从性轨迹：持续每日（7剂/周）、持续高剂量（4-6剂/周）、高剂量但下降（从平均4-6剂/周开始，然后下降）和持续低剂量（少于2剂/周）。498名每天坚持服药的妇女中，没有一人感染艾滋病毒。在658名持续高剂量的妇女中，只有1人感染了艾滋病毒（发病率，0.13/100人-年）。高剂量但下降组（n = 1166）的妇女中艾滋病发病率为0.49/100人-年，持续低剂量组（n = 632）的妇女中为1.27/100人-年。

综上，在对顺性别妇女中11项PrEP F/TDF批准后研究的汇总分析中，艾滋病总发病率为0.72/100人年；对PrEP具有持续每日或持续高剂量的高依从性（4-6剂/周）的女性经历了非常低的HIV发病率。

附：英文原文

Title: HIV Preexposure Prophylaxis With Emtricitabine and Tenofovir Disoproxil Fumarate Among Cisgender Women

Author: Jeanne Marrazzo, Li Tao, Marissa Becker, Ashley A. Leech, Allan W. Taylor, Faith Ussery, Michael Kiragu, Sushena Reza-Paul, Janet Myers, Linda-Gail Bekker, Juan Yang, Christoph Carter, Melanie de Boer, Moupali Das, Jared M. Baeten, Connie Celum

Issue&Volume: 2024-03-01

Abstract:

Importance  Emtricitabine and tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP) is highly effective in cisgender men who have sex with men (MSM) when adherence is high (>4 doses/week). Real-world effectiveness and adherence with F/TDF for PrEP in cisgender women is less well characterized.

Objective  To characterize the effectiveness of F/TDF for PrEP and its relationship with adherence in cisgender women.

Design, Setting, and Participants  Data were pooled from 11 F/TDF PrEP postapproval studies conducted in 6 countries that included 6296 cisgender women aged 15 to 69 years conducted from 2012 to 2020. HIV incidence was evaluated according to adherence level measured objectively (tenofovir diphosphate concentration in dried blood spots or tenofovir concentration in plasma; n=288) and subjectively (electronic pill cap monitoring, pill counts, self-report, and study-reported adherence scale; n=2954) using group-based trajectory modeling.

Exposures  F/TDF prescribed orally once a day. HIV incidence was analyzed in subgroups based on adherence trajectory.

Main Outcomes and Measures  HIV incidence.

Results  Of the 6296 participants, 46% were from Kenya, 28% were from South Africa, 21% were from India, 2.9% were from Uganda, 1.6% were from Botswana, and 0.8% were from the US. The mean (SD) age at PrEP initiation across all studies was 25 (7) years, with 61% of participants being younger than 25 years. The overall HIV incidence was 0.72 per 100 person-years (95% CI, 0.51-1.01; 32 incident HIV diagnoses among 6296 participants). Four distinct groups of adherence trajectories were identified: consistently daily (7 doses/week), consistently high (4-6 doses/week), high but declining (from a mean of 4-6 doses/week and then declining), and consistently low (less than 2 doses/week). None of the 498 women with consistently daily adherence acquired HIV. Only 1 of the 658 women with consistently high adherence acquired HIV (incidence rate, 0.13/100 person-years [95% CI, 0.02-0.92]). The incidence rate was 0.49 per 100 person-years (95% CI, 0.22-1.08) in the high but declining adherence group (n=1166) and 1.27 per 100 person-years (95% CI, 0.53-3.04) in the consistently low adherence group (n=632).

Conclusions and Relevance  In a pooled analysis of 11 postapproval studies of F/TDF for PrEP among cisgender women, overall HIV incidence was 0.72 per 100 person-years; individuals with consistently daily or consistently high adherence (4-6 doses/week) to PrEP experienced very low HIV incidence.

DOI: 10.1001/jama.2024.0464

Source: https://jamanetwork.com/journals/jama/fullarticle/2816036