Landmark FDA Approval: Twice-Yearly Lenacapavir Offers New Hope in HIV Prevention
A novel approach to HIV prevention has received FDA approval, offering a significant advancement in pre-exposure prophylaxis (PrEP). Lenacapavir (Yeztugo; Gilead Sciences), a first-in-class capsid inhibitor, will be available as a twice-yearly subcutaneous injection, providing a long-acting alternative to daily oral PrEP and existing injectable options. The approval, granted in June 2025, is based on compelling data demonstrating up to 100% efficacy in diverse, high-risk populations.
A New Mechanism of Action for Enhanced Prevention
Originally developed for individuals with treatment-resistant HIV, lenacapavir’s potential in prevention was unlocked through the PURPOSE 1 and PURPOSE 2 trials. According to an infectious disease physician at Whitman-Walker Medical Clinic, lenacapavir’s unique mechanism of action—targeting the viral capsid—sets it apart from other PrEP strategies. This novel approach, combined with its long-acting profile, addresses critical barriers to consistent PrEP use.
Exceptional Efficacy Demonstrated in Global Trials
The PURPOSE 1 trial, conducted in Uganda and South Africa, focused on cisgender women and adolescent girls, a population often underrepresented in HIV prevention research. The results were striking: zero HIV infections occurred among the 2134 participants receiving lenacapavir during the blinded phase, translating to 100% efficacy when compared to daily oral PrEP.
PURPOSE 2, a broader study encompassing approximately 3200 participants in the U.S. and other countries—including men who have sex with men, gender nonbinary individuals, transgender women, and transgender men—demonstrated 99.9% efficacy in preventing HIV acquisition. These findings collectively support the expanded use of lenacapavir as a powerful tool in the fight against HIV.
Addressing Adherence and Stigma with a Flexible Approach
A significant challenge in HIV prevention is adherence to PrEP regimens. Data from IQVIA prescription databases reveal that PrEP persistence is only around 40% at six months, with many individuals discontinuing treatment. Lenacapavir’s twice-yearly formulation directly addresses this issue.
“Offering people choice and autonomy can overcome traditional barriers to persistence,” one expert explained. “A one-size-fits-all approach doesn’t work in prevention.” The less frequent injection schedule is particularly beneficial for individuals who struggle with daily adherence, experience “pill fatigue,” face stigma associated with carrying oral PrEP, or have privacy concerns. Furthermore, lenacapavir provides an alternative for those who are averse to injections, offering a subcutaneous option compared to the currently approved intramuscular cabotegravir.
Ensuring Equitable Access and Maximizing Impact
While the FDA approval represents a major step forward, broader adoption and a robust support infrastructure are crucial to ensure equitable access to lenacapavir. Health systems and insurers must prioritize coverage, and alternative delivery models should be implemented to reach individuals who may face barriers to traditional healthcare settings.
The success of lenacapavir will depend on a commitment to follow-up care and retention programs, ensuring that individuals remain engaged with the PrEP regimen. By meeting patients where they are and providing discreet, effective options, lenacapavir has the potential to significantly bend the epidemic curve for HIV and improve the lives of those at risk.
