Breaking barriers in HIV management: the rise of long-acting lenacapavir

Human immunodeficiency virus type 1 (HIV-1) remains a global health challenge, affecting over 38 million people as of 2024. The recent FDA approval of lenacapavir (Yeztugo®) on 18 June 2025 marks a significant advance in prevention and treatment. Lenacapavir is the first-in-class, long-acting HIV-1 capsid inhibitor, administered twice yearly via subcutaneous injection for pre-exposure prophylaxis in adults and adolescents ≥35 kg. It targets the capsid protein, disrupting multiple stages of the viral lifecycle without cross-resistance to existing antiretrovirals. Clinical trials (CAPELLA, CALIBRATE) demonstrated robust efficacy, with up to 94% viral suppression when combined with active agents and sustained CD4+ gains. Its prolonged half-life, minimal drug-drug interactions, and convenient dosing improve adherence, privacy, and healthcare access - critical in high-incidence, resource-limited settings. Ongoing PURPOSE trials are evaluating its role in high-risk populations. Lenacapavir's favorable safety profile and public health potential support its integration into evolving HIV management and prevention strategies, potentially accelerating progress toward epidemic control.