Background
Twice-yearly subcutaneous (SC) lenacapavir (LEN) for HIV pre-exposure prophylaxis (PrEP) showed high efficacy and a favorable safety profile in cisgender women in PURPOSE 1 (NCT04994509). We present updated HIV incidence, seroconversion, and safety data through the end of the randomized blinded phase.
Methods
PURPOSE 1 is an ongoing Phase 3, double-blind, active-controlled, randomized trial evaluating the efficacy of twice-yearly SC LEN for HIV PrEP among cisgender adolescent girls and young women in South Africa and Uganda. Participants were randomized 2:2:1 to receive SC LEN every 26 weeks, daily oral emtricitabine–tenofovir alafenamide (F/TAF), or daily oral emtricitabine–tenofovir disoproxil fumarate (F/TDF; active control), with corresponding placebos. The primary efficacy analysis included data through May 29, 2024. Following release of these results, participants completed final randomized blinded phase visits on a rolling basis through October 22, 2024, with the option to join the LEN open-label extension. We summarize HIV incidence and adverse events through the end of the randomized blinded phase and describe HIV seroconversion data in the LEN group.
Results
Among 5338 participants who initially tested negative for HIV, there were 23 additional HIV infections after the primary analysis. Of these, 2 were in the LEN group, 13 in the F/TAF group and 8 in the F/TDF group (Fig). A total of 78 incident HIV infections were observed through the end of the randomized blinded phase: 2 among 2134 participants in the LEN group (0.07/100 person-years [PY]; 95% CI: 0.01-0.26]), 52 among the 2136 participants in the F/TAF group (1.98/100 PY; 95% CI: 1.48-2.60), and 24 among 1068 participants in the F/TDF group (1.86/100 PY; 95% CI: 1.19-2.77). Of the two participants assigned to LEN with incident HIV infections, participant A received all LEN injections on time (last dose 182 days prior to diagnosis) and had a LEN concentration of 44.6 ng/mL at diagnosis (above target inhibitory quotient 4 [IQ4]); participant B received LEN 487 days prior to diagnosis and had a LEN concentration of 0.65 ng/mL at diagnosis (below target IQ4). No new safety concerns with LEN were reported and the incidence of injection-site reactions (ISRs) in the LEN group was similar to that of the primary analysis, with no new discontinuations due to ISRs.
Conclusions
In this updated analysis with longer follow-up, twice-yearly SC LEN remained safe, well tolerated and highly efficacious for HIV PrEP among cisgender women.
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