Key Takeaways
- First and only twice-yearly pre-exposure prophylaxis (PrEP) approved in United States: The FDA has approved Gilead’s Yeztugo (lenacapavir) as the first injectable HIV prevention option offering six months of protection with just two doses per year.
- Clinical trials show near-complete HIV prevention: Phase III data from PURPOSE 1 and 2 showed ≥99.9% efficacy, with Yeztugo outperforming daily oral Truvada and showing a strong safety profile.
- Opportunity to improve PrEP uptake and adherence: Yeztugo’s long-acting formulation may overcome barriers such as stigma, low awareness, and poor adherence to daily PrEP, especially in underserved populations.
The FDA has approved Gilead Sciences’ Yeztugo (lenacapavir) as the first and only twice-yearly injectable option for HIV pre-exposure prophylaxis (PrEP) in adults and adolescents weighing at least 77 lbs. According to the company, the treatment offers six months of protection with just two injections per year. Approval was based on results from the Phase III PURPOSE 1 and 2 trials, which demonstrated that Yeztugo was superior to daily oral Truvada in both cisgender women and diverse populations, including men and gender-diverse individuals.1
How Could a Twice-Yearly Injection Transform HIV Prevention in the United States?
“This is a historic day in the decades-long fight against HIV,” said Daniel O’Day, chairman, CEO, Gilead Sciences, in a press release. “Yeztugo is one of the most important scientific breakthroughs of our time and offers a very real opportunity to help end the HIV epidemic. This is a medicine that only needs to be given twice a year and has shown remarkable outcomes in clinical studies, which means it could transform HIV prevention. Gilead scientists have made it their life’s work to end HIV and now, with the FDA approval of Yeztugo and in collaboration with our many partners, we can help to make that goal a reality.”
PURPOSE 1 and 2 Trial Design
- The double-blinded, multicenter, randomized PURPOSE 1 and PURPOSE 2 trials evaluated the safety and efficacy of twice-yearly subcutaneous (SC) Yeztugo.
- PURPOSE 1 included 5,368 adolescent girls and young women at risk for HIV infection, while PURPOSE 2 consisted of 3,295 cisgender men, transgender women, transgender men, and gender nonbinary people ≥16 who have sex with male partners.
- The primary endpoints of both studies were background HIV incidence reported per 100-person-years and the number of participants with diagnosis of HIV-1 infection.2,3
Results and Safety Profile
- Results from PURPOSE 1 showed that no HIV infections occurred among the 2,134 participants receiving twice-yearly SC Yeztugo, demonstrating a 100% reduction in infections and superiority over daily oral Truvada.
- Results from PURPOSE 2 showed that only two HIV infections occurred, with 99.9% remaining HIV-negative. Both trials achieved superiority over daily oral PrEP as well as background HIV incidence rates.
- The safety profile of Yeztugo was reported to be well tolerated.
- Common adverse events included injection site reactions, headache, and nausea.1
Public Health Context and HIV Burden in the United States
There are approximately 1.2 million people currently living with HIV in the United States, including 13% who are unaware of their status. In 2022, around 31,800 people were diagnosed with HIV in the United States. However, new HIV infections decreased 12%, from 36,300 in 2018 to 31,800 in 2022. Among people aged 13 years and older, there were 37,981 new cases in the United States and its six associated territories.4
Addressing Barriers to PrEP Uptake
“Yeztugo could be the transformative PrEP option we’ve been waiting for—offering the potential to boost PrEP uptake and persistence and adding a powerful new tool in our mission to end the HIV epidemic,” said Carlos del Rio, MD, distinguished professor of medicine, dvision of infectious diseases, Emory University School of Medicine, co-director, Emory Center for AIDS Research in Atlanta, in the press release. “A twice-yearly injection could greatly address key barriers like adherence and stigma, which individuals on more frequent PrEP dosing regimens, especially daily oral PrEP, can face. We also know that, in research, many people who need or want PrEP preferred less frequent dosing.”
Global Outlook and Next Steps
While Yeztugo is currently only approved in the United States, regulatory filings are underway in several countries, including those in the EU, South America, and Africa.1
References
1.Yeztugo® (Lenacapavir) Is Now the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection. Gilead. June 18, 2025. Accessed June 19, 2025. https://www.gilead.com/news/news-details/2025/yeztugo-lenacapavir-is-now-the-first-and-only-fda-approved-hiv-prevention-option-offering-6-months-of-protection
2. Pre-Exposure Prophylaxis Study of Lenacapavir and Emtricitabine/Tenofovir Alafenamide in Adolescent Girls and Young Women at Risk of HIV Infection (PURPOSE 1). Clinicaltrials.gov. Accessed June 19, 2025. https://clinicaltrials.gov/study/NCT04994509
3. Study of Lenacapavir for HIV Pre-Exposure Prophylaxis in People Who Are at Risk for HIV Infection (PURPOSE 2). Clinicaltrials.gov. Accessed June 19, 2025. https://clinicaltrials.gov/study/NCT04925752?cond=HIV&term=purpose%202&rank=1
4. U.S. Statistics. HIV.gov. Accessed June 19, 2025. https://www.hiv.gov/hiv-basics/overview/data-and-trends/statistics
