392. Favorable Adherence and Safety of Twice-Yearly Subcutaneous Lenacapavir for PrEP Among PURPOSE 2 Participants Who Used Substances

作者：Jesse ClarkAllison Agwu, Susan P Buchbinder, Jill Blumenthal, Nittaya Phanuphak, Joanne Batting, Michelle S Cespedes, Beatriz Grinsztejn, Javier R. Lama, Karam Mounzer, Priyanka Arora, Leo Brown, Christoph C Carter, Sara Greco Thomas Häussler Katharina Lobinger Sébastien Salerno, R. Singh, Pamela Wong, Carlo Hojilla, Susanne Doblecki‐Lewis · 发表于：Open Forum Infectious Diseases · 年份：2026 · DOI：10.1093/ofid/ofaf695.130 · 被引用次数：1 · 研究领域：HIV/AIDS drug development and treatment、HIV/AIDS Research and Interventions、HIV Research and Treatment

Abstract Background Cisgender men and gender-diverse individuals with a high likelihood of HIV acquisition are disproportionately affected by substance use, which can affect HIV pre-exposure prophylaxis (PrEP) adherence. Twice-yearly subcutaneous (SC) lenacapavir (LEN) showed high efficacy and safety for PrEP in PURPOSE 2 (NCT04925752). We investigated the impact of substance use on LEN adherence and safety in PURPOSE 2. As LEN is an inhibitor of CYP3A, an enzyme involved in fentanyl metabolism, we developed a physiologically based pharmacokinetic (PBPK) model to evaluate this potential drug–drug interaction. Methods Substance use was defined as any self-reported drug use, stimulant use, and opioid use in the 12 weeks prior to baseline, and/or binge drinking (≥ 6 drinks on 1 occasion). Adherence (on-time injections) and safety (adverse events [AEs]) through the primary analysis were compared across participants reporting different types of substance use and those reporting no substance use. Prior in vitro, clinical, and published fentanyl PK data were used to develop a PBPK model to evaluate the impact of LEN on fentanyl concentrations. Results Of 2183 participants randomized to LEN, 767/2061 (37.2%) reported any drug use, 17/2092 (0.8%) injected drugs, 409/2058 (19.9%) used stimulants, 33/2086 (1.6%) used opioids, and 841/2074 (40.5%) had monthly or more binge-drinking episodes at baseline. LEN adherence was high and comparable across substance use types and to participants ...