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
Year: 2026
Type: article
Study design: Clinical Trial
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 (HIV) 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 comparator for 20 months. RESULTS: In total, 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). Overall, 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 1 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 infections occurred in either group during the double-blind phase. CONCLUSIONS: 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.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciag171
Authors: Raphael J Landovitz, Yvett Pinedo, Federico Hinestrosa, Gordon E Crofoot, Cynthia Brinson, Susan Buchbinder, Jean-Michel Molina, Ronnie M Gravett, James B Brock, Moti N Ramgopal, A Lina Rosengren, Igho Ofotokun, Jose Valdez Madruga, Geoffroy Liegeon, Ravindre Panchia, Khuanchai Supparatpinyo, Anchalee Avihingsanon, Catherine Creticos, Shobha Swaminathan, Susanne Doblecki-Lewis, Jorge Rodriguez, Marc Siegel, Shinichi Oka, Thanyawee Puthanakit, Beatriz Grinsztejn, Eduard J Sanders, Javier R Lama, Johannes Lombaard, Nkosiphile Ndlovu, Peggy Hwang, Jiejun Du, Beth Jackson, Brenda Homony, Barbara Evans, Peter Sklar, Michael N Robertson, Rebeca M Plank
Institutions: University of California, Los Angeles, Via Libre, Orlando Immunology Center, San Francisco Department of Public Health, Inserm, Université Paris Cité, Assistance Publique – Hôpitaux de Paris, Hôpital Lariboisière, Hôpital Saint-Louis, University of Alabama at Birmingham, University of Mississippi Medical Center, University of North Carolina at Chapel Hill, Emory University, Infection, Anti-microbiens, Modélisation, Evolution, University of the Witwatersrand, Perinatal HIV Research Unit, Chiang Mai University, Chulalongkorn University, HIV Netherlands Australia Thailand Research Collaboration, Howard Brown Health Center, Rutgers New Jersey Medical School, University of Miami, George Washington University, National Center for Global Health and Medicine, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Aurum Institute, Asociación Civil Impacta Salud y Educación, Merck & Co., Inc., Rahway, NJ, USA (United States)
Language: English
Subfield: Infectious Diseases
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
OpenAlex ID: W7135378055