Lenacapavir serves its PURPOSE in young individuals

Twice-yearly subcutaneous (SC) lenacapavir demonstrates high efficacy, favourable safety, and consistent pharmacokinetics (PK) as pre-exposure prophylaxis (PrEP) for HIV-negative youth (aged 16–25 years) in an analysis of the phase III PURPOSE 1 (P1) and PURPOSE 2 (P2) trials.

“In P1, zero HIV infections occurred in youth on lenacapavir, indicating 100 percent efficacy. In P2, there were two,” said Dr Katherine Gill from the Desmond Tutu HIV Centre, University of Cape Town in South Africa, at IAS 2025. These translated to HIV incidences of 0 and 0.10 per 100 person-years (PY) for P1 and P2, respectively.

These were markedly lower than the HIV incidences per 100 PY with F/TAF* (2.02 [39 infections]) and F/TDF** (1.69 [16 infections]) in P1 and that with F/TDF (0.93 [nine infections]) in P2.

“Adverse events (AEs) and laboratory abnormalities were generally comparable in youth receiving lenacapavir in both studies,” said Gill, adding that these aligned with the known effects of lenacapavir.

Overall, the incidences of grade ≥3 AEs were between 3 and 7 percent, while serious AE rates were <4 percent. The rates of drug discontinuation due to AEs were low at <1 percent across all age subgroups. [IAS 2025, abstract 3476]

In P1, the most common AEs were headache and genitourinary chlamydia infection in participants <18 years and urinary tract and genitourinary chlamydia infections among those ≥18 years. In P2, the most common were anal chlamydia infection and anal and oropharyngeal gonococcal infections across both age subgroups (≤25 and >25 years).

Injection site reactions led to drug discontinuation in 30 participants (four in P1 and 26 in P2), but these were predominantly low-grade and aligned with those reported in both study populations, noted Gill.

The observed lenacapavir plasma levels were also generally comparable between youths and adults, she added.

Youth disproportionately affected by HIV

Youth are disproportionately affected by HIV and account for a significant number of new HIV infections globally, Gill noted. “They account for ~28 percent of the 1.3 million new HIV infections annually and face significant barriers to starting and staying on daily oral PrEP.” [https://aidsinfo.unaids.org; accessed 24 July 2025; AIDS Behav 2019;23:2719-2729; Arch Sex Behav 2021;50:1729-1742; BMC Womens Health 2024;24:665]

“While ethical and regulatory safeguards are intended to protect adolescents, they often delay access to critical innovations. A more balanced, inclusive approach is essential to ensure timely, equitable prevention options for this vulnerable group,” said Gill.

“Lenacapavir, a first-in-class, long-acting, multistage HIV-1 capsid inhibitor, offers a promising alternative with high potency and a long half-life administered twice yearly subcutaneously,” she continued.

In P1, 5,338 cisgender women aged 16-25 years were randomized 2:2:1 to SC lenacapavir every 26 weeks, oral F/TAF daily, or oral F/TDF daily. P2 randomized 3,265 cisgender men and gender-diverse individuals aged ≥16 years 2:1 to lenacapavir or F/TDF. Across both studies, 2,892 youths received the investigational drug.

Expand access to effective HIV prevention

With only two HIV seroconversions in P2 and a safety and PK profile that aligns with those reported in adults, the current findings support efficacy extrapolation across age groups, noted Gill. “The findings provide unprecedented insight into long-acting PrEP use among adolescents and young adults.”

According to Gill, both trials are “the most globally and demographically diverse PrEP efficacy trials to date … This broad representation enhances the generalizability of the findings and underscores lenacapavir’s potential to reduce the HIV prevention needs of disproportionately affected populations worldwide.”

“[The findings] highlight lenacapavir’s promise as a long-acting PrEP option to address adherence challenges and reduce HIV infections in young individuals. Adolescents will not be left behind. These data offer real hope for expanding access to effective prevention,” Gill concluded.