Twice-Yearly Injectable Pre-Exposure Prophylaxis With Lenacapavir: Redefining Adherence and Access in the Global Fight Against HIV

Abstract

Despite progress in human immunodeficiency virus (HIV) prevention, global targets remain unmet, with over 1.3 million new infections annually—driven by adherence challenges, stigma, and daily pill fatigue linked to oral pre-exposure prophylaxis (PrEP). Lenacapavir, a long-acting injectable capsid inhibitor approved by the FDA in June 2025, offers transformative twice-yearly subcutaneous dosing with sustained efficacy and minimal drug interactions. PURPOSE 1 and 2 trials demonstrated near-complete protection across cisgender women, men who have sex with men, transgender individuals, and adolescents, highlighting its potential to overcome barriers to PrEP uptake. Its high acceptability, infrequent dosing, and pharmacologic durability make it ideal for individuals facing stigma, mobility constraints, or limited healthcare access. WHO's endorsement marks a pivotal milestone, but real-world implementation must address cold-chain logistics, cost, provider training, and systemic inequities. Integrating lenacapavir through decentralized delivery models, differentiated care, and inclusive national guidelines will be key to equitable access, decreasing gaps and advancing epidemic control.