Twice-yearly SC lenacapavir is a transformative PrEP option for gay and bisexual individuals, and other MSM.Twice-yearly subcutaneous lenacapavir continues to show high efficacy and is well tolerated among cisgender men and gender-diverse individuals in the open-label extension (OLE) of the PURPOSE 2 trial.
At week 52, only one new HIV incidence was reported among participants who were on continuous lenacapavir from randomization to the OLE, translating to an HIV incidence of 0.09 per 100 person-years (PY). Among those who switched from oral pre-exposure prophylaxis (PrEP) to lenacapavir, there were none (HIV incidence per 100 PY, 0.00).
These findings suggest that HIV incidence per 100 PY on lenacapavir remained stable compared with the primary analysis (0.10 [n=2]) and the end of the randomized blinded phase (RBP; 0.11 [n=1]). The control group had a total of 12 new HIV cases by the end of the RBP. [AIDS 2026, abstract OAC2806LB]
“Combining all lenacapavir PYs, the HIV incidence was 0.07 per 100 PY [or four out of 3,004 participants],” said Dr Marcelo Losso from Hospital General de Agudos José María Ramos Mejía, Buenos Aires, Argentina, at AIDS 2026.
Dr Marcelo Losso from Hospital General de Agudos José María Ramos Mejía, Buenos Aires, Argentina.The safety and tolerability of lenacapavir were comparable between the continuous and switch lenacapavir groups, as reflected by the similar rates of any grade ≥3 adverse event (AE; 8 percent vs 4 percent), serious AEs (7 percent vs 3 percent), AEs leading to discontinuation of study regimen (<1 percent vs 0 percent), and injection site reactions (ISRs; grade 2: 24 percent vs 21 percent; grade 3: 1 percent vs <1 percent).
In the continuous and switch lenacapavir groups, the most common grade 3 ISR was pain (0.2 percent and 0.1 percent), while the most common AEs were oropharyngeal gonococcal infection (25 percent and 18 percent), anal chlamydia infection (25 percent and 17 percent), and anal gonococcal infection (21 percent and 15 percent).
Furthermore, on-time injection adherence to open-label lenacapavir was high at 93–94 percent.
A transformative PrEP option
“Men and gender-diverse individuals are populations that are disproportionately affected by the HIV pandemic,” Losso noted. In a UNAIDS report, approximately 20 percent of new HIV cases reported in 2022 occurred in gay and bisexual individuals and in other men who have sex with men (MSM) aged 15–49 years worldwide. [https://www.unaids.org/sites/default/files/media_asset/2024-unaids-global-aids-update_en.pdf, accessed 2 September 2026]
Compared with cisgender individuals, the odds of acquiring HIV are higher among transmasculine individuals (seven times more), and even more so among transfeminine individuals (66 times more). [PLoS One 2021;16:e0260063]
PURPOSE 2 comprised 3,265 HIV-negative cisgender men and gender-diverse individuals aged ≥16 years. A majority of the participants were from South America (Brazil: 36 percent; Peru: 14 percent; Argentina: 7 percent). The rest were from the US (21 percent), Thailand (12 percent), South Africa (11 percent), and Mexico (<1 percent).
In the RBP, participants received either SC lenacapavir (n=2,179) or emtricitabine/tenofovir disoproxil fumarate (n=1,086) every 26 weeks. In the OLE, 95 percent of participants continued or switched to SC lenacapavir twice a year.
The median follow-up was 117 weeks in the continuous lenacapavir group and 65 weeks in the switch lenacapavir group.
“With longer-term follow-up, lenacapavir remained highly efficacious and well tolerated, which confirms data from the primary analysis and through the end of the RBP,” Losso noted. [N Engl J Med 2025;392:1261-1276]
“The extended data through 52 weeks of the OLE in PURPOSE 2 and >5,000 PY of follow-up reinforce twice-yearly SC lenacapavir as a transformative PrEP option for gay and bisexual individuals, and other MSM,” Losso concluded.