— Only one person developed HIV infection in year-long extensions of two PURPOSE trials
August 1, 2026
• 3 min read
Only one person has developed a new HIV infection during a year-long extension of the landmark PURPOSE 1 and PURPOSE 2 trials testing twice-yearly injectable lenacapavir (Yeztugo) for pre-exposure prophylaxis (PrEP), according to twin open-label extensions.
There were no new HIV cases in the PURPOSE 1 52-week open-label extension among adolescent girls and young women in South Africa and Uganda. That extension included 2,136 patients who remained on lenacapavir after the trial’s randomized blinded phase ended, and 2,496 patients who switched at the extension’s start to lenacapavir from either daily oral emtricitabine and tenofovir alafenamide (Descovy) or emtricitabine and tenofovir disoproxil fumarate (Truvada).
Including the two HIV infections that happened in the lenacapavir group during PURPOSE 1’s randomized blinded phase, the post-extension HIV incidence including all lenacapavir person-time was 0.03 per 100 person-years (95% CI 0.00-0.10). The incidence rate was 0.00 (95% CI 0.00-0.13) among those who switched to lenacapavir for the extension, reported Noah Kiwanuka, MBChB, PhD, of Makerere University School of Public Health in Kampala, Uganda, at the International AIDS Conference (IAC) in Rio de Janeiro.
“As an investigator at one of the study sites, I must say that it has been a good experience to see us removed from seeing women getting infected with HIV in the randomized study phase to zero HIV infections in the open-label phase,” Kiwanuka said.
The PURPOSE 2 52-week open-label extension saw only one new HIV infection among the cisgender men and transgender or gender-nonbinary persons who continued treatment. That new case was among the 1,587 patients who remained on lenacapavir; there were no new HIV cases among the 827 patients who switched from daily oral PrEP to lenacapavir.
The HIV incidence rate combining all lenacapavir person-time for the two extension groups was 0.07 per 100 person-years (95% CI 0.02-0.18). The rate was 0.09 (95% CI 0.02-0.22) among those taking lenacapavir during both the PURPOSE 2 randomized blinded phase and the extension, while those who switched from daily oral PrEP to lenacapavir for the extension period saw a rate of 0.00 (95% CI 0.00-0.38), reported Marcelo Losso, MD, of Hospital General de Agudos J. M. Ramos Mejía in Buenos Aires, Argentina, in a separate IAC presentation.
“After 30 years providing care at a public hospital for people living with HIV, it’s a privilege to be part of an initiative that provided innovation for the people who need it,” Lasso noted.
The PURPOSE 1 and PURPOSE 2 trials showed lenacapavir was highly effective in preventing HIV infection.
In PURPOSE 1, PrEP with injectable lenacapavir every 26 weeks reduced HIV incidence by 100% compared with daily oral emtricitabine and tenofovir disoproxil fumarate and background HIV incidence.
In cisgender men and transgender or gender-nonbinary persons, PURPOSE 2 found that twice-a-year lenacapavir cut the rate of HIV infections by a relative 89% compared with daily oral emtricitabine and tenofovir disoproxil fumarate, with rates of 0.10 versus 0.93 per 100 person-years.
Last year, the FDA approved lenacapavir as PrEP to reduce the risk of sexually acquired HIV-1 in at-risk adults and adolescents, and the CDC PrEP Guidelines Work Group strongly recommended its PrEP use.
Safety and tolerability were similar in the two open-label extensions. In PURPOSE 1, 7% of the continuous-treatment group and 5% of the switch group had serious adverse events (AEs), but less than 1% of each group had an AE that led to treatment discontinuation. Injection-site reactions leading to treatment discontinuation happened in less than 1% of either group.
PURPOSE 2 saw serious AEs in 7% of the continuous-treatment group and 3% of the switch group, with AEs causing treatment discontinuation in less than 1% and 0% of the two groups, respectively. Injection-site reactions led to treatment discontinuation in 1% of the continuous-treatment group and 0% of the switch group.
In both extensions, adherence was high among patients who’d switched from daily oral PrEP to lenacapavir. In PURPOSE 1, 97% of those in the switch group received the third lenacapavir injection, as did 92% of the PURPOSE 2 switch group.
