Key takeaways:
- Data from the phase 3 PURPOSE 2 trial presented at IDWeek 2025 showed that lenacapavir (Yextugo; Gilead) can be safely used with gender-affirming hormone therapy (GAHT) without affecting hormone levels or drug efficacy through 26 weeks.
- Pharmacokinetic analyses found no clinically significant drug–drug interactions between lenacapavir and either estrogen- or testosterone-based regimens, indicating no need for dose adjustments.
- The trial, which included over 480 gender-diverse participants, confirmed lenacapavir’s strong HIV prevention efficacy, with only 2 infections reported in the treatment arm.
- Investigators emphasized that these findings support lenacapavir as a safe and effective PrEP option for transgender and gender-diverse individuals, a population disproportionately affected by HIV.
According to data from the phase 3 PURPOSE 2 study, presented at the 2025 IDWeek Annual Meeting in Atlanta, Georgia, phase 3 PURPOSE 2 study, concomitant use of lenacapavir (Yextugo; Gilead) with gender-affirming hormone therapy (GAHT) did not have any impact on either their efficacy or have any clinically significant drug–drug Interactions through 26 weeks.1
“In a subset of participants assigned male at birth and taking estradiol (n=115) or assigned female at birth and taking testosterone (n=25), GAHT concentrations at weeks 13 and 26 were comparable with baseline (pre-dosing) levels, irrespective of dose, frequency, or any changes in dosing. [Population pharmacokinetic effects] PopPK analyses demonstrated that GAHT co-administration did not have a statistically significant impact on [lenacapavir] LEN PK,” the study’s authors wrote.1
“There was no effect of lenacapavir on either estrogen containing or testosterone containing regimens, no decrement in estradiol or testosterone levels, which suggests that the hormones work just as well in people taking lenacapavir with no dose adjustment,” said study coauthor Jill Blumenthal, MD, MAS, professor in the Division of Infectious Diseases and Global Public Health in the Department of Medicine at UC San Diego Health.
PURPOSE 2 is a randomized, controlled trial that studied the efficacy of twice-yearly lenacapavir PrEP in cisgender men, transgender women, transgender men, and gender nonbinary individuals for 26 weeks. The analyses assessed the impact of feminizing or masculinizing GAHT on lenacapavir PK compared with lenacapavir PK in participants not taking GAHT.1
Of the 2183 participants who received lenacapavir, 486 (22.3%) self-identified as gender diverse; 315 (14.4%) transgender women; 29 (1.3%) transgender men; 136 (6.2%) gender nonbinary; and 6 (0.3%) other gender. Concomitant GAHT use was reported by 253 (11.6%) participants.
A high-risk population for HIV
Transgender individuals have a disproportionately higher likelihood of HIV acquisition, and additional barriers to care, so it is vital for this population to have tools such as effective PrEP.2
In terms of lenacapavir’s overall efficacy in the transgender population, Blumenthal confirms its ability to prevent HIV. “Purpose 2 findings were extraordinary. [There were] only 2 infections in the treatment arm in the Purpose 2 study. There were over 20% of transgender individuals who were included…I feel very comfortable saying that this is a medication that works well for transgender individuals based on these study findings,” she said.
References:
1.Blumenthal J, et al. No Clinically Significant Drug–Drug Interactions with Co-administration of Feminizing or Masculinizing Hormone Therapy and Twice-yearly Lenacapavir PrEP in Gender-Diverse Persons. Poster presented at IDWeek 2025. October 19-22, 2025. Atlanta, GA.
2. Kanny D, Lee K, Olansky E, et al. Overview and Methodology of the National HIV Behavioral Surveillance Among Transgender Women - Seven Urban Areas, United States, 2019-2020. MMWR Suppl. 2024;73(1):1-8. Published 2024 Jan 25. doi:10.15585/mmwr.su7301a1
