Lenacapavir injections administered twice yearly dropped new HIV infections to near zero during a year-long open-label extension of the PURPOSE 1 and PURPOSE 2 clinical trials, according to data presented at the International AIDS Conference in Rio de Janeiro. Researchers reported that out of thousands of participants worldwide, only a single individual contracted a new HIV infection while receiving the twice-yearly drug regimen.
PURPOSE 1 Open-Label Extension Yields Zero New Infections in South Africa and Uganda
The PURPOSE 1 extension enrolled 2,136 adolescent girls and young women who stayed on lenacapavir after the randomized blinded phase ended. Another 2,496 patients switched to lenacapavir at the start of the extension from daily oral emtricitabine and tenofovir alafenamide, known as Descovy, or emtricitabine and tenofovir disoproxil fumarate, known as Truvada, according to trial data presented by Noah Kiwanuka, MBChB, PhD, of Makerere University School of Public Health in Kampala, Uganda.
There were zero new HIV cases recorded during the 52-week extension among participants in South Africa and Uganda. When including the two infections that occurred in the lenacapavir group during the randomized blinded phase, the post-extension HIV incidence across all lenacapavir person-time reached 0.03 per 100 person-years, with a 95% confidence interval of 0.00 to 0.10. For participants who switched to lenacapavir specifically for the open-label phase, the incidence rate dropped to 0.00.
“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 during his presentation at the conference.
PURPOSE 2 Extension Records One New Case Among Men and Gender-Diverse Participants
In the parallel PURPOSE 2 trial extension, cisgender men and transgender or gender-nonbinary persons experienced just one new HIV infection across a full year of treatment, according to Marcelo Losso, MD, of Hospital General de Agudos J. M. Ramos Mejía in Buenos Aires, Argentina. That single new infection occurred among the 1,587 patients who maintained continuous lenacapavir treatment from the initial blinded phase. The 827 patients who switched from daily oral pre-exposure prophylaxis to lenacapavir at the start of the extension saw zero new HIV cases.
Combining all lenacapavir person-time for both PURPOSE 2 extension groups resulted in an overall HIV incidence rate of 0.07 per 100 person-years, with a 95% confidence interval ranging from 0.02 to 0.18. Participants taking lenacapavir continuously through both phases registered an incidence rate of 0.09, whereas those who transitioned from daily oral PrEP reported a rate of 0.00.
“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,” Losso noted in his presentation.
Did you know?
Lenacapavir is marketed under the brand name Yeztugo and requires only two injections per year, offering a distinct dosing schedule compared to standard daily oral prevention pills.
Efficacy Comparisons Against Daily Oral Regimens
The open-label extensions follow the primary findings of the landmark PURPOSE 1 and PURPOSE 2 trials, which established the high efficacy of twice-yearly injectable lenacapavir. In PURPOSE 1, the biannual injection schedule reduced HIV incidence by 100% compared against background incidence and daily oral emtricitabine and tenofovir disoproxil fumarate. In PURPOSE 2, focused on cisgender men and transgender or gender-nonbinary individuals, biannual lenacapavir cut the rate of HIV infections by a relative 89% compared with daily oral emtricitabine and tenofovir disoproxil fumarate, yielding rates of 0.10 versus 0.93 per 100 person-years.
The FDA approved lenacapavir as PrEP to lower the risk of sexually acquired HIV-1 among at-risk adults and adolescents, and the CDC PrEP Guidelines Work Group issued a strong recommendation supporting its clinical use.
Safety, Tolerability, and High Adherence Rates
Both open-label extensions tracked participant safety and medication adherence closely. In PURPOSE 1, serious adverse events occurred in 7% of the continuous-treatment group and 5% of the switch group. Adverse events leading to treatment discontinuation affected less than 1% of participants in either cohort, and injection-site reactions caused discontinuation in under 1% of patients.
Similarly, PURPOSE 2 recorded serious adverse events in 7% of continuous-treatment patients and 3% of switch patients. Treatment discontinuation due to adverse events occurred in less than 1% of the continuous group and 0% of the switch group, while injection-site reactions drove discontinuation in 1% of continuous-treatment participants and 0% of switch participants.
Adherence remained notably high among individuals who transitioned from daily oral regimens to the injectable therapy. In the PURPOSE 1 switch group, 97% of participants successfully received their third lenacapavir injection, while 92% of the PURPOSE 2 switch group hit the same adherence milestone.
Frequently Asked Questions
How often is lenacapavir administered for HIV prevention?
Lenacapavir is given as an injection twice a year, specifically every 26 weeks, according to trial protocols and federal approval guidelines.
Did participants switching from daily pills to injections maintain good adherence?
Yes. Data from the open-label extensions showed that 97% of switch participants in PURPOSE 1 and 92% in PURPOSE 2 received their third scheduled lenacapavir injection.
What were the main side effects reported in the extensions?
Serious adverse events occurred in 3% to 7% of participants depending on the cohort, though fewer than 1% of patients across all groups stopped treatment due to adverse events or injection-site reactions.
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