Lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor, demonstrated 100% efficacy in preventing human immunodeficiency virus (HIV) infection in cisgender adolescent girls and young women in a phase III trial, according to results published in The New England Journal of Medicine.
The study, called PURPOSE 1 and funded by Gilead Sciences, was a randomized, double-blind trial which enrolled 5,345 HIV-negative cisgender adolescent girls and young women aged 16-26 years at 28 sites in South Africa and Uganda. Participants were randomized 2:2:1 to receive either subcutaneous lenacapavir every 26 weeks, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF). In the primary efficacy analysis, lenacapavir reduced HIV incidence by 100% compared to both background HIV incidence (incidence rate ratio [IRR] 0.00, 95% confidence interval [CI], 0.00-0.04, P<0.001) and F/TDF (IRR 0.00, 95% CI, 0.00-0.10, P<0.001).
Researchers found that among 2,134 participants receiving lenacapavir, there were 0 infections over 1,939 person-years (incidence 0/100 person-years, 95% CI 0.00-0.19). In contrast, the background HIV incidence in the screened population was 2.41/100 person-years (95% CI, 1.82-3.19), and HIV incidence was 2.02/100 person-years (95% CI, 1.44-2.76) in the F/TAF group and 1.69/100 person-years (95% CI, 0.96-2.74) in the F/TDF group.
HIV incidence with F/TAF did not differ significantly from background incidence (IRR 0.84, 95% CI, 0.55-1.28, P=0.21) or F/TDF (IRR 1.20, 95% CI, 0.67-2.14). Adherence to F/TAF and F/TDF was low, with most participants having tenofovir diphosphate levels consistent with less than two doses per week. In the F/TAF group, those with medium/high adherence had lower odds of acquiring HIV compared to those with low adherence (odds ratio, 0.11, 95% CI, 0.01-0.49).
No new safety concerns were identified. Injection-site reactions were more common with lenacapavir (68.8%) than placebo injections (34.9%), but were mostly mild and rarely led to discontinuation (0.2%). Serious adverse events occurred in 2.8%, 4.0%, and 3.3% of patients in the lenacapavir, F/TAF, and F/TDF groups, respectively.
The trial included 510 pregnancies among 487 participants, with no concerning safety signals. It is also the first adult HIV prevention trial to enroll adolescents, with 124 participants aged 16 or 17 years.
Experts state these results demonstrate lenacapavir's potential to address gaps in pre-exposure prophylaxis (PrEP) uptake and adherence for women globally. If approved, lenacapavir would be the first twice-yearly PrEP option. Gilead has announced plans to prioritize access and enable efficient regulatory pathways in resource-limited countries that have high HIV incidence rates. Results from the PURPOSE 2 trial, which enrolled men who have sex with men, transgender women, and gender non-binary individuals, are expected in late 2024 or early 2025.
Complete disclosure forms are available in the study.
