RCT: Twice-Yearly Lenacapavir Prevents HIV Infections More Effectively Than Daily F/TAF in Women – N Engl J Med

Study Design and Population: This phase 3, double-blind, randomized controlled trial included 5,338 adolescent girls and young women in South Africa and Uganda. Participants were assigned to receive either twice-yearly subcutaneous lenacapavir, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF) as an active control, with corresponding placebos.

Main Findings: Lenacapavir demonstrated superior efficacy in HIV prevention, with zero infections observed among its recipients. In contrast, the F/TAF group experienced 39 HIV infections (2.02 per 100 person-years), while the F/TDF group had 16 infections (1.69 per 100 person-years). HIV incidence was significantly lower with lenacapavir compared to background incidence and F/TDF, while no significant difference was observed between F/TAF and F/TDF.

Implications for Practice: Twice-yearly lenacapavir could be a more effective and potentially easier-to-adopt HIV prevention strategy than daily oral F/TAF in cisgender women, though considerations of injection-site reactions are necessary. This approach could improve adherence and outcomes in populations with low persistence in daily PrEP use.

Reference: Bekker, L.-G., Das, M., Abdool Karim, Q., Ahmed, K., Batting, J., Brumskine, W., Gill, K., et al. (2024). Twice-yearly lenacapavir or daily F/TAF for HIV prevention in cisgender women. New England Journal of Medicine, 391(7), 648-659. DOI: 10.1056/NEJMoa2407001.