Lenacapavir pre-exposure prophylaxis (PrEP) can safely be given to transgender and gender-diverse persons who are receiving gender-affirming hormone therapy (GAHT), according to recent study findings presented at IDWeek 2025.
Study coauthor Jill Blumenthal, MD, MAS, of the University of California San Diego, presented the results of PURPOSE 2, the most gender-inclusive phase 3 clinical trial for HIV prevention to date, during a poster session.
Previous research showed concern over potential drug-drug interactions between PrEP and GAHT, that could prevent these individuals from using PrEP to lower their risk of getting HIV. In this study, Blumenthal and colleagues examined the pharmacokinetic (PK) effects of co-administration of masculinizing and feminizing GAHT with twice-yearly subcutaneous lenacapavir PrEP in more than 2,000 people.
Participants self-reported gender identity at baseline, with 2486 saying they were gender diverse. They identified as transgender women (n=315), transgender men (n=29), gender nonbinary (n=136), and other gender (n=6). At each study visit, data on GAHT use was collected by the researchers.
For 26 weeks, plasma/serum concentrations of estradiol, testosterone, and dihydrotestosterone were evaluated in the gender-diverse subset of participants who received lenacapavir and uninterrupted estradiol or testosterone. The researchers then used Population PK analyses to assess any effect of GAHT on lenacapavir PrEP comparing results with participants who received PrEP but not GAHT.
Nearly 12% of participants reported concomitant GAHT use. Among those assigned male at birth taking estradiol (n=115) and those assigned female at birth taking testosterone (n=25), GAHT concentrations at weeks 13 and 26 remained consistent with baseline values, regardless of dose, frequency, or dosing adjustments.
Overall, the researchers found no clinically significant effect of lenacapavir coadministration on feminizing or masculinizing GAHT concentrations or a significant impact on PrEP, which leads to supporting the use of both in gender-diverse individuals who are at high risk for HIV infection.
Reference
Blumenthal J, et al. IDWeek 2025. P-305
