Gilead Sciences, Inc., announced a breakthrough in human immunodeficiency virus (HIV) prevention with U.S. Food and Drug Administration (FDA) approval of Yeztugo (lenacapavir), a once-every-six-month, long-acting injectable for pre-exposure prophylaxis (PrEP) against sexually transmitted HIV-1. This marks the first and the only biannual PrEP treatment approved for use in U.S. adults and adolescents weighing at least 35 kilograms.
With this authorisation, Yeztugo brings a revolutionary change in HIV protection, providing a discreet and convenient option to daily oral PrEP. Data from clinical trials based on the Phase 3 PURPOSE 1 and 2 studies revealed that more than 99% of people who received Yeztugo remained HIV-negative at the end of the study, highlighting its strong efficacy in reducing HIV risk.
Daniel O Day, Gilead Sciences CEO and Chairman, defined the decision of the FDA as a turning point in the fight against HIV. “Yeztugo represents a revolution in HIV prevention. This will allow providing effective protection only two times a year, and this medicine can remove the long-standing barriers to PrEP access and use, he added. “We are proud to take this step forward with the most affected communities.”
Although the first oral PrEP drug has been available since 2012, uptake in the U.S. has been inconsistent. The 2022 data provided by the CDC showed that 35% of those eligible individuals were using PrEP. Â Stigma, lack of adherence, and education have contributed to disproportionately low usage among women, people of color, as well as in the South of the U.S.
Yeztugo (lenacapavir) injection (463.5 mg/1.5 mL) has been approved by the U.S. FDA to be used in the PrEP of sexually acquired HIV-1 in adults and adolescents weighing ≥35 kg. The initiation must be with a confirmed negative HIV-1 test based on an FDA-approved diagnostic test for acute or primary HIV infection.
A boxed warning emphasizes the risk of developing drug-resistant HIV-1 when used in undiagnosed individuals. Yeztugo should not be used in patients with an unknown or a confirmed positive HIV-1 status. To minimize this risk, regular HIV testing prior to every dose is essential. If HIV-1 infection occurs during treatment, patients should be switched to a complete HIV regimen.
Yeztugo belongs to a comprehensive prevention strategy, including regular dosing, safer sex practices, and addressing behavioural and biological risk factors such as sex without condoms, sexually transmitted infections (STIs), and high-prevalence environments. Due to its long half-life, adherence to the dosing schedule is critical; lenacapavir remains in the body for up to a year.
Initiation consists of two subcutaneous injections (totalling 927 mg) and a two-day course of oral lenacapavir. Subsequent injections are given every six months. In case of delay, it can be taken in the form of interim weekly oral tablets up to 6 months. However, if oral coverage lapses beyond 28 weeks, reinitiation of the full regimen is necessary.
Common side effects include injection site reactions, headache, and nausea. There are potentially important drug interactions with CYP3A modulators that require dosage adjustments.
Developed by Gilead Sciences, a global leader in HIV research, Yeztugo is poised to be a significant advancement in preventing new HIV infections and scaling up access to effective prevention.
References: Gilead Sciences. Yeztugo® (lenacapavir) is now the first and only FDA-approved HIV prevention option offering 6 months of protection. Published June 18, 2025. Accessed June 20, 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
