Article and Study Summary:
Article
Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women
Published in:
N Engl J Med. 2024;391(13):1179–1192. https://doi.org/10.1056/NEJMoa2407001
Authors:
Bekker L, Das M, Abdool Karim Q, et al. for the PURPOSE I Study Team.
Summary
This phase 3, multi-center, double-blind, randomized, active-controlled trial (PURPOSE 1) evaluated the efficacy and safety of twice-yearly subcutaneous lenacapavir or daily oral emtricitabine-tenofovir alafenamide (F/TAF) as pre-exposure prophylaxis (PrEP) for HIV prevention in adolescent girls and young women (AGYW) in South Africa and Uganda. HIV-negative AGYW aged 16 to 25 years who were sexually active with male partners and not using PrEP were randomized in a 2:2:1 ratio to receive subcutaneous lenacapavir every 26 weeks, daily oral F/TAF, or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) as an active control. All participants also received subcutaneous or oral placebo. The primary outcome was the efficacy of lenacapavir and F/TAF to prevent HIV infection, assessed by comparison to the estimated background HIV incidence in the screened population and HIV incidence in the F/TDF group. Among 5,338 randomized participants, 55 incident HIV infections were observed: 0 in the lenacapavir group (0 per 100 person-years; 95% confidence interval [CI] 0.00-0.19), 39 in the F/TAF group (2.02 per 100 person-years; 95% CI 1.44-2.76), and 16 in the F/TDF group (1.69 per 100 person-years; 95% CI 0.96-2.74). HIV incidence with lenacapavir was, therefore, significantly lower than background HIV incidence and HIV incidence with F/TDF. HIV incidence with F/TAF did not differ significantly from background HIV incidence (incidence rate ratio 0.84; 95% CI 0.55-1.28) or HIV incidence with F/TDF (incidence rate ratio 1.20; 95% CI 0.67-2.14), and adherence to F/TAF and F/TDF was low. No safety concerns were found, but injection-site reactions were more common in the lenacapavir group than in the placebo injection group, with four participants discontinuing lenacapavir due to injection-site reactions. The randomized, blinded phase of the trial was stopped early after an interim efficacy analysis. Lenacapavir could have a substantial impact on global HIV prevention efforts if it is made available for the most at-risk populations as it is a highly efficacious PrEP option that is long-acting and discreet.
Full Synopsis:
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