Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons

- This phase 3, double-blind, randomized, active-controlled trial (PURPOSE 2) evaluated the efficacy and safety of twice-yearly subcutaneous lenacapavir versus daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) in 3265 cisgender men and gender-diverse individuals at high risk of HIV. Over a median follow-up of 52 weeks, HIV incidence was dramatically lower in the lenacapavir group (0.10 per 100 person-years) compared to both the background rate (2.37) and the F/TDF group (0.93), representing a 96% and 89% reduction, respectively. Adherence to lenacapavir was high; most participants received injections on time. Adverse events were similar across groups, though injection-site nodules and discomfort were more common with lenacapavir. Two participants in the lenacapavir group acquired HIV—both exhibited emergent drug resistance. The findings suggest that lenacapavir, with biannual dosing, could transform HIV prevention for populations with barriers to daily PrEP adherence

- This phase 3, double-blind, randomized, active-controlled trial (PURPOSE 2) evaluated the efficacy and safety of twice-yearly subcutaneous lenacapavir versus daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) in 3265 cisgender men and gender-diverse individuals at high risk of HIV. Over a median follow-up of 52 weeks, HIV incidence was dramatically lower in the lenacapavir group (0.10 per 100 person-years) compared to both the background rate (2.37) and the F/TDF group (0.93), representing a 96% and 89% reduction, respectively. Adherence to lenacapavir was high; most participants received injections on time. Adverse events were similar across groups, though injection-site nodules and discomfort were more common with lenacapavir. Two participants in the lenacapavir group acquired HIV—both exhibited emergent drug resistance. The findings suggest that lenacapavir, with biannual dosing, could transform HIV prevention for populations with barriers to daily PrEP adherence