Pre-Exposure Prophylaxis Study of Lenacapavir in Cisgender Men, Transgender Women, Transgender Men, and Gender Nonbinary People at Risk for HIV Infection

Summary

The goal of this study is to evaluate the efficacy of the study drugs, lenacapavir (LEN) in preventing HIV infection, in participants ≥ 16 years of age who have condomless receptive anal sex with partners assigned male at birth and are at risk for HIV-1 infection. The primary objective of this study is to evaluate the efficacy of LEN for HIV-1 pre-exposure prophylaxis (PrEP) in participants ≥ 16 years of age who have condomless receptive anal sex with partners assigned male at birth at risk of HIV-1 infection.

Timeline

Start

2021-06-28

Primary completion

2024-08-21

Completion

2028-08

Outcome

Met primary endpoint

registry analysis (superiority test); Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF vs Incidence Phase: All Screened Participants With Non-missing HIV-1 Diagnosis; p <0.0001; Rate Ratio 0.043 NCT04925752 ↗

release “At interim analysis, the independent Data Monitoring Committee (DMC) confirmed that the PURPOSE 2 trial met its key efficacy endpoints” gilead.com ↗

release “PURPOSE 2 is the second pivotal Phase 3 trial to demonstrate superior efficacy for twice-yearly lenacapavir for the investigational use of HIV prevention as PrEP” gilead.com ↗

release “In both trials, twice-yearly lenacapavir also demonstrated superiority of prevention of HIV infections when compared with once-daily oral Truvada®” gilead.com ↗

release “demonstrating 99.9% of participants did not acquire HIV infection and superiority of prevention of HIV infections” gilead.com ↗

Publications

• Background Kelley CF, Acevedo-Quiñones M, Agwu AL, et al. Twice-yearly lenacapavir PrEP in cisgender gay men, transgender women and men, and gender-diverse people (PURPOSE 2). Presented at: HIV Drug Therapy Glasgow; November 10-13, 2024; Glasgow, United Kingdom.
• Background Kelley CF, Acevedo-Quinones M, Agwu AL, Avihingsanon A, Benson P, Blumenthal J, Brinson C, Brites C, Cahn P, Cantos VD, Clark J, Clement M, Creticos C, Crofoot G, Diaz RS, Doblecki-Lewis S, Gallardo-Cartagena JA, Gaur A, Grinsztejn B, Hassler S, Hinojosa JC, Hodge T, Kaplan R, Lacerda M, LaMarca A, Losso MH, Valdez Madruga J, Mayer KH, Mills A, Mounzer K, Ndlovu N, Novak RM, Perez Rios A, Phanuphak N, Ramgopal M, Ruane PJ, Sanchez J, Santos B, Schine P, Schreibman T, Spencer LY, Van Gerwen OT, Vasconcelos R, Vasquez JG, Zwane Z, Cox S, Deaton C, Ebrahimi R, Wong P, Singh R, Brown LB, Carter CC, Das M, Baeten JM, Ogbuagu O; PURPOSE 2 Study Team. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. N Engl J Med. 2025 Apr 3;392(13):1261-1276. doi: 10.1056/NEJMoa2411858. Epub 2024 Nov 27.
• Background Cespedes M, Das M, Hojilla JC, Blumenthal J, Mounzer K, Ramgopal M, Hodge T, Torres TS, Peterson C, Shibase S, Elliott A, Demidont AC, Callaghan L, Watson CC, Carter C, Kintu A, Baeten JM, Ogbuagu O. Proactive strategies to optimize engagement of Black, Hispanic/Latinx, transgender, and nonbinary individuals in a trial of a novel agent for HIV pre-exposure prophylaxis (PrEP). PLoS One. 2022 Jun 3;17(6):e0267780. doi: 10.1371/journal.pone.0267780. eCollection 2022.
• Background Cantos Lucio VD, Mngadi K, Supparatpinyo K, et al. From Breakthroughs to Backbones: The Evolving Landscape of HIV PrEP. Presented at: Conference on Retroviruses and Opportunistic Infections (CROI 2026); February 22-25, 2026; Denver, CO. Abstract 129.
• Kwan TH, Chan DPC, Lee SS. Utilisation of HIV pre-exposure prophylaxis and preferences of alternative long-acting modalities among men who have sex with men in Hong kong: a cross-sectional study. BMC Public Health. 2025 Dec 26;26(1):361. doi: 10.1186/s12889-025-26025-5.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Lenacapavir	Small molecule	927 mg	Oral
Subject	Tenofovir disoproxil fumarate	Small molecule	—	Oral
Background	emtricitabine	Other / unclassified	—	Oral
Background	emtricitabine	Other / unclassified	—	Oral
Background	tenofovir alafenamide	Small molecule	—	Oral

Indications

No indication recorded.