Lenacapavir (Sunlenca), Gilead Sciences’ twice-yearly capsid inhibitor, demonstrated 100% efficacy for HIV prevention in a large study of young cisgender women in Africa. Oral PrEP is highly effective for people who can take it consistently, but additional options are still needed for people who have difficulty using daily pills. The Phase III PURPOSE 1 trial enrolled more than 5,300 women in South Africa and Uganda. They were randomly assigned to receive injectable lenacapavir once every six months or the daily PrEP pills Descovy (tenofovir alafenamide/emtricitabine) or Truvada (tenofovir disoproxil fumarate/emtricitabine) in a 2:2:1 ratio. There were zero new infections in the lenacapavir group, 39 in the Descovy group and 16 in the Truvada group. All three PrEP methods were well tolerated, and no new safety concerns were identified. A parallel study (PURPOSE 2) is testing lenacapavir PrEP for cisgender and transgender men, trans women and nonbinary people in the United States and six other countries; results are expected in late 2024 or early 2025.