Safety and Tolerability of Oral Islatravir Once Monthly as Pre-Exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study

Authors

• Raphael J. Landovitz, UCLA Center for Clinical AIDS Research and Education, Los Angeles, CA,  USA.
• Yvett Pinedo, Via Libre,  Lima, Peru.
• Federico Hinestrosa, Orlando Immunology Center, Orlando, FL,  USA.
• Gordon E. Crofoot, The Crofoot Research Center, Houston, TX,  USA.
• Cynthia Brinson, Central Texas Clinical Research, Austin, TX,  USA.
• Susan Buchbinder, San Francisco Department of Health, San Francisco, CA,  USA.
• Jean-Michel Molina, Paris Cité University, Paris, France; Assistance Publique, Hôpitaux de Paris, Hôpitaux Saint Louis et Lariboisière, Paris, and INSERM UMR1342, France.
• Ronnie M. Gravett, University of Alabama at Birmingham, Birmingham, AL,  USA.
• James B. Brock, University of Mississippi Medical Center, Jackson, MS,  USA.
• Moti N. Ramgopal, Midway Immunology and Research Center, Fort Pierce, FL,  USA.
• A Lina Rosengren, The University of North Carolina at Chapel Hill, Chapel Hill, NC,  USA.
• Igho Ofotokun, Emory University School of Medicine, Atlanta, GA,  USA.
• Jose Valdez Madruga, Centro de Referência e Treinamento DST/AIDS-SP, São Paulo,  Brazil.
• Geoffroy Liegeon, Paris Cité University, Paris, France; Assitance Publique - Hôpitaux de Paris, Hôpitaux Saint Louis et Lariboisière, Paris, France and INSERM UMR 1137 IAME - Team PreViST , Paris,  France.
• Ravindre Panchia, Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS, University of the Witwatersrand, Johannesburg,  South Africa.
• Khuanchai Supparatpinyo, Chiang Mai University, Chiang Mai, Thailand.
• Anchalee Avihingsanon, HIV-NAT, Thai Red Cross AIDS and Infectious Diseases Research Centre and Center of Excellence in Tuberculosis, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
• Catherine Creticos, Howard Brown Health Center, Chicago, IL,  USA.
• Shobha Swaminathan, Rutgers New Jersey Medical School, Newark, NJ,  USA.
• Susanne Doblecki-Lewis, University of Miami Miller School of Medicine, Miami, FL,  USA.
• Jorge Rodriguez, Global Research Institute, Los Angeles, CA,  USA.
• Marc Siegel, George Washington University School of Medicine and Health Sciences, Washington, DC,  USA.
• Shinichi Oka, National Center for Global Health and Medicine, Tokyo,  Japan.
• Thanyawee Puthanakit, Chulalongkorn University, Bangkok,  Thailand.
• Beatriz Grinsztejn, Evandro Chagas National Institute of Infectious Diseases-Fiocruz, Rio de Janeiro,  Brazil.
• Eduard J. Sanders, Aurum Institute, Johannesburg,  South Africa.
• Javier R. Lama, Asociación Civil Impacta Salud y Educación, Lima, Peru.
• Johannes Lombaard, Josha Research, Bloemfontein,  South Africa.
• Nkosiphile Ndlovu, Wits RHI, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg,  South Africa.
• Peggy Hwang, Merck & Co., Inc., Rahway, NJ,  USA.
• Jiejun Du, Merck & Co., Inc., Rahway, NJ,  USA.
• Beth Jackson, Merck & Co., Inc., Rahway, NJ,  USA.

Document Type

Journal Article

Publication Date

3-14-2026

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

DOI

10.1093/cid/ciag171

Keywords

HIV-1 prevention; PrEP; cisgender men; islatravir; transgender women

Abstract

BACKGROUND: Islatravir once monthly (qm), a nucleoside reverse transcriptase translocation inhibitor with a long half-life, was evaluated for safety and tolerability in cisgender men and transgender women who have sex with men and are at increased likelihood of HIV-1 exposure. METHODS: IMPOWER-24 (NCT04652700) was a double-blind, Phase 3 study. Participants were randomized 2:1 to islatravir 60 mg oral qm or emtricitabine (FTC; 200 mg) coformulated with either tenofovir disoproxil (245 mg) or tenofovir alafenamide (TAF; 25 mg) once daily (qd). After ∼9 months, blinded islatravir was discontinued due to lymphocyte reductions; participants were offered open-label FTC/tenofovir disoproxil or FTC/TAF qd for 20 months. RESULTS: 494 participants were enrolled (328 islatravir; 166 comparator): 91.5% were cisgender men, 41.7% were White, and median age was 27 years. Mean blinded dosing duration was 4.7 months (islatravir) versus 4.3 months (comparator). 211 participants (64.3%) in the islatravir group and 128 (77.1%) in the comparator group had ≥1 adverse event (AE). Most AEs were mild or moderate, with one AE leading to product discontinuation (islatravir; gastroesophageal reflux). Serious AEs occurred in <2%; none were related to study product. Change in total lymphocytes in the islatravir group at Month 3 was -7.4%; a trend toward recovery was observed after islatravir was stopped. Mean total lymphocytes remained within normal range. No HIV-1 infections occurred in either group during the double-blind phase. CONCLUSION: Islatravir qm was generally well-tolerated; decreases in total lymphocytes were observed with islatravir. Original primary efficacy objectives were not assessed due to early study stoppage.

APA Citation

Landovitz, Raphael J.; Pinedo, Yvett; Hinestrosa, Federico; Crofoot, Gordon E.; Brinson, Cynthia; Buchbinder, Susan; Molina, Jean-Michel; Gravett, Ronnie M.; Brock, James B.; Ramgopal, Moti N.; Rosengren, A Lina; Ofotokun, Igho; Valdez Madruga, Jose; Liegeon, Geoffroy; Panchia, Ravindre; Supparatpinyo, Khuanchai; Avihingsanon, Anchalee; Creticos, Catherine; Swaminathan, Shobha; Doblecki-Lewis, Susanne; Rodriguez, Jorge; Siegel, Marc; Oka, Shinichi; Puthanakit, Thanyawee; Grinsztejn, Beatriz; Sanders, Eduard J.; Lama, Javier R.; Lombaard, Johannes; Ndlovu, Nkosiphile; Hwang, Peggy; Du, Jiejun; and Jackson, Beth, "Safety and Tolerability of Oral Islatravir Once Monthly as Pre-Exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study" (2026). GW Authored Works. Paper 8879.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/8879

Department

Medicine