Lenacapavir HIV Prevention: Zero Infections in Landmark PURPOSE-1 Trial

A long-acting injectable medication for HIV prevention has demonstrated 100% efficacy in a pivotal Phase 3 clinical trial, offering a potential shift in pre-exposure prophylaxis (PrEP) for high-risk populations.

The drug, lenacapavir, is a twice-yearly injectable HIV-1 capsid inhibitor developed by Gilead Sciences. Results from the PURPOSE 1 trial showed that no participants receiving the twice-yearly injections acquired an HIV infection over the course of one year.

The study included 2,134 cisgender adolescent girls and young women. The findings indicate that lenacapavir’s efficacy was significantly higher than both the background HIV incidence and the results for participants receiving once-daily oral Truvada (emtricitabine and tenofovir disoproxil fumarate; F/TDF).

Clinical Trial Outcomes and Superiority

The PURPOSE 1 trial met its key efficacy endpoints by demonstrating the superiority of twice-yearly lenacapavir over daily oral PrEP. Because of the zero-infection result, an independent Data Monitoring Committee recommended that Gilead stop the blinded phase of the trial at the interim analysis to offer open-label lenacapavir to all participants.

According to Gilead Sciences, This represents the first Phase 3 HIV prevention trial to ever show zero infections. Merdad Parsey, MD, PhD, Chief Medical Officer at Gilead Sciences, stated that the drug has demonstrated its potential as an important new tool to help prevent HIV infections.

The broader PURPOSE program is described as the most comprehensive and diverse HIV prevention trial program ever conducted, consisting of five different studies to evaluate the drug across various populations.

Development of Once-Yearly Formulations

Following the success of the twice-yearly dosing, Gilead has advanced research into even longer-acting versions of the medication. On March 11, 2025, the company presented Phase 1 data at the Conference on Retroviruses and Opportunistic Infections (CROI 2025) and published findings in The Lancet regarding two novel, once-yearly formulations of lenacapavir.

The Phase 1 study focused on intramuscular injections. The data indicated that these once-yearly formulations achieved and maintained plasma concentrations that exceed those associated with the efficacy observed in the PURPOSE 1 and PURPOSE 2 trials.

Based on these results, Gilead announced plans to launch a Phase 3 study for once-yearly lenacapavir in the second half of 2025.

Regulatory Status and Public Health Impact

The FDA has signed off on lenacapavir as a long-acting PrEP medication. This regulatory approval signals a transition toward long-acting options that reduce the burden of daily pill adherence, which has historically been a challenge in HIV prevention.

The shift from daily oral medication to a twice-yearly injection may improve access and consistency of protection, particularly for adolescent girls and young women in geographically diverse regions.

Additional data from the PURPOSE program has also explored participant preference, showing a preference for twice-yearly lenacapavir over once-daily oral options. The program continues to analyze pharmacokinetic, safety, and efficacy data specifically within adolescent populations.