Breakthrough Trial Results: PURPOSE 1 and PURPOSE 2

On 20 November 2024, Gilead Sciences released final data from its pivotal HIV prevention trials, PURPOSE 1 and PURPOSE 2, evaluating lenacapavir—a long-acting injectable administered every six months. In PURPOSE 1, which enrolled cisgender women in sub-Saharan Africa, the drug achieved 100% efficacy: no HIV infections occurred in the treatment arm. PURPOSE 2, which included cisgender men, transgender individuals, and non-binary participants, showed a 96% reduction in HIV incidence compared to background rates.

These results position lenacapavir as a game-changing alternative to daily oral PrEP, especially for populations with historically low adherence. The drug’s pharmacokinetics allow for sustained protection with minimal intervention, addressing a major barrier in HIV prevention.

Global Access Strategy: Licensing and Equity

In response to the trial’s success, Gilead announced plans to issue voluntary licenses for generic manufacturing of lenacapavir in low- and middle-income countries. The initiative aims to expand access across sub-Saharan Africa, where HIV prevalence remains high and daily PrEP adherence is inconsistent.

Global health organizations, including UNAIDS and the Medicines Patent Pool, praised the move as a model for equitable drug distribution. The World Health Organization is expected to update its HIV prevention guidelines to include long-acting injectables, pending regulatory approvals in key regions.

Implications for Clinical Research and Public Health

Lenacapavir’s success is expected to influence future trial designs in infectious disease prevention. Researchers are exploring its use in post-exposure prophylaxis (PEP), as well as combination strategies with vaccines and monoclonal antibodies. The trial also sets a precedent for inclusive enrollment, with PURPOSE 2 featuring robust representation of transgender and non-binary participants.

Public health experts note that lenacapavir could help close persistent gaps in HIV prevention, particularly among young women, sex workers, and LGBTQ+ communities. Its approval may also accelerate interest in other long-acting agents for diseases where adherence is a challenge, including tuberculosis and hepatitis B.