Gilead Sciences has received a highly anticipated approval from the FDA for its long-acting HIV prevention injection, YEZTUGO (lenacapavir), marking a significant advancement in HIV prevention. On June 18, 2025, the FDA approved YEZTUGO, an injectable HIV-1 capsid inhibitor, for use as pre-exposure prophylaxis (PrEP) in adults and adolescents weighing at least 35 kg to help prevent sexually transmitted HIV. 

This makes YEZTUGO the first and only PrEP option in the US that is administered just twice a year. YEZTUGO becomes the second long-acting PrEP drug available on the market, alongside GSK and ViiV’s Apretude, which received FDA approval in 2021 for bi-monthly administration.

Lenacapavir has received approval in several countries for use alongside other antiretrovirals in treating adults with multidrug-resistant HIV. In the United States, it is also authorized to lower the risk of sexually acquired HIV in adults and adolescents weighing at least 35 kg who are at risk of infection.

Unlike most antivirals that target a single stage of the HIV lifecycle, lenacapavir operates through a multi-stage mechanism, setting it apart from existing drug classes. It has demonstrated no in vitro cross-resistance to currently approved antiretroviral therapies.

“This marks a pivotal moment in the decades-long battle against HIV,” said Daniel O’Day, Chairman and CEO of Gilead Sciences. “YEZTUGO represents one of the most significant scientific advancements of our time, offering a real chance to bring the HIV epidemic to an end. As a twice-yearly treatment with impressive clinical results, it has the potential to revolutionize HIV prevention. Gilead’s scientists have dedicated their careers to ending HIV, and with the FDA’s approval of YEZTUGO and support from our many partners, we are now closer to turning that vision into reality.”

Lenacapavir is being studied as a long-acting therapeutic option across various ongoing and upcoming early- and late-phase clinical trials within Gilead’s broader HIV prevention and treatment pipeline. The aim is to establish lenacapavir as a core component of future HIV regimens, either as a standalone agent or in combination, with flexible dosing formats, including long-acting oral and injectable options, tailored to the unique needs and preferences of people and communities living with or at risk of HIV. 

Lenacapavir, previously approved in 2022 and marketed as SUNLENCA, was initially indicated for patients with treatment-resistant HIV who had undergone prior therapies. Despite its availability, data from the Centers for Disease Control and Prevention (CDC) indicate that in 2022, the latest year with reported figures, only 36% of eligible individuals in the US received any form of PrEP. Usage remains uneven across the population, with particularly low adoption rates among women, Black/African American and Hispanic/Latino communities, and residents of the US South. 

Contributing factors to this limited uptake include difficulties with adherence, persistent stigma, and a lack of awareness about available PrEP options, both among healthcare providers and potential users. These challenges are particularly concerning given that over 100 new HIV diagnoses were recorded daily in the US in 2023. Unlike earlier PrEP treatments such as Gilead’s once-daily TRUVADA, the newly approved YEZTUGO is designed for use by all individuals at risk of HIV and requires dosing only once every six months.

“YEZTUGO has the potential to be a game-changing PrEP option, one that could significantly improve both uptake and long-term use, while serving as a vital new tool in the effort to end the HIV epidemic,” said Dr. Carlos del Rio, Distinguished Professor of Medicine at Emory University School of Medicine and Co-Director of the Emory Center for AIDS Research. “With just two injections a year, this approach could help overcome major challenges such as adherence and stigma, which are often issues with more frequent dosing like daily oral PrEP. Research also shows that many individuals at risk for HIV prefer less frequent dosing options.”

The FDA has approved Gilead’s New Drug Applications (NDAs) for YEZTUGO, based on data from the Phase III PURPOSE 1 and PURPOSE 2 studies led by Gilead. In the PURPOSE 1 trial (NCT04994509), the primary analysis showed that twice-yearly subcutaneous YEZTUGO resulted in zero HIV infections among 2,134 participants, achieving a 100% reduction in HIV incidence and demonstrating superior protection compared to daily oral TRUVADA (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg; F/TDF) in cisgender women in sub-Saharan Africa. 

Similarly, in the PURPOSE 2 trial (NCT04925752), only two HIV infections occurred among 2,179 participants in the YEZTUGO group, meaning 99.9% of participants remained HIV-free. YEZTUGO again outperformed daily oral TRUVADA, this time in a broader population including cisgender men and gender-diverse individuals across various global locations.

In both studies, YEZTUGO not only surpassed TRUVADA in preventing HIV but also outperformed background HIV incidence (bHIV). The drug was generally well-tolerated, with no significant or unexpected safety issues. Findings from both trials were published in The New England Journal of Medicine, and the drug’s performance led Science to name lenacapavir its 2024 “Breakthrough of the Year.”

YEZTUGO was approved by the FDA through a Priority Review process. Additionally, in October 2024, it received Breakthrough Therapy Designation, a status meant to accelerate the development and review of drugs showing substantial improvements over existing treatments.

The approval of YEZTUGO adds another achievement to Gilead’s strong HIV portfolio. While the company is also active in areas like oncology and liver disease, HIV treatments, particularly BIKTARVY, still account for the bulk of its revenue. Although Gilead hasn’t disclosed exact sales projections for YEZTUGO, it anticipates a significant expansion of the PrEP market once the drug becomes available, as many individuals who haven’t yet started PrEP are reportedly waiting for this option.

In the US, Gilead is actively collaborating with insurers, healthcare providers, and other payers to secure widespread insurance coverage for YEZTUGO. For individuals with eligible commercial insurance, Gilead’s Advancing Access Co-Pay Savings Program may lower out-of-pocket expenses to as little as zero.

Additionally, Gilead is dedicated to supporting uninsured individuals in accessing YEZTUGO. Through its Advancing Access medication assistance program, the company will offer YEZTUGO at no cost to those who qualify.

Outside the United States, Gilead is implementing an access strategy shaped by input from global health advocates and organizations. This approach emphasizes speed and efficiency in securing regulatory approval and access to twice-yearly lenacapavir for PrEP. The company has submitted both a Marketing Authorization Application (MAA) and an EU-M4all application to the European Medicines Agency (EMA), both of which have been validated and will undergo expedited review. 

Gilead has also sought regulatory approval in Australia, Brazil, Canada, and South Africa. Following the FDA approval of YEZTUGO, Gilead is preparing additional submissions in countries that recognize FDA decisions, such as Argentina, Mexico, and Peru. The company will continue to provide updates on future regulatory filings.