Today’s MMWR report strongly recommends injectable lenacapavir (LEN) every 6 months as an HIV preexposure prophylaxis (PrEP) option for people ≥35 kg (≥77 lb), expanding the 2021 CDC guidance that previously included two oral tenofovir-based regimens and injectable cabotegravir. The recommendation is based on the PURPOSE-1 and PURPOSE-2 randomized trials, which reported LEN efficacy of 100% in females and 96% in a primarily male population over 52 weeks versus background incidence/no PrEP.1
The CDC PrEP Guidelines Work Group used the GRADE approach and found high certainty of evidence for both efficacy and safety. No major safety signals were identified; the most common adverse events were mild to moderate injection-site reactions.1
Public health impact centers on adherence. Because persistence with existing PrEP regimens is often suboptimal, a twice-yearly injection could improve uptake and continuation, particularly for patients who struggle with daily pills or more frequent injections, thereby strengthening prevention outcomes.1
What You Need To Know
CDC now strongly recommends twice-yearly injectable lenacapavir as a PrEP option, expanding guidance beyond oral tenofovir regimens and cabotegravir for people who weigh at least 35 kg.
PURPOSE-1 and PURPOSE-2 showed lenacapavir prevented HIV infection with 100% efficacy in females and 96% in a primarily male population over 52 weeks, with mostly mild to moderate injection-site reactions.
A six-month dosing interval may improve adherence and persistence compared with daily pills or more frequent injections, with potential to strengthen HIV prevention outcomes.
Background News
September 6, 2025 - PEPFAR and Gilead Partnership
PEPFAR and Gilead will deliver twice-yearly lenacapavir PrEP to up to 2 million people in low-resource countries over three years, supplied at no profit until generics scale, an access push to improve adherence and reduce HIV incidence as approvals and WHO prequalification advance.2
June 18, 2025 - FDA Approval
The FDA approved lenacapavir (Yeztugo), the first and only twice-yearly injectable PrEP option, supported by the phase 3 PURPOSE 1 and PURPOSE 2 trials. These trials demonstrated 96% to 100% efficacy in preventing HIV across diverse populations. In an interview with Contagion, Jared Baeten, MD, PhD, senior vice president of clinical development and virology at Gilead Sciences, highlighted lenacapavir’s potential to overcome adherence and stigma barriers associated with daily oral PrEP.3
Listen to our full interview from the approval: FDA Approves Gilead’s Twice-Yearly Injectable Lenacapavir (Yeztugo) for HIV Prevention
July 9, 2025 - Global Fund Partnership
Gilead announced a three-year partnership with the Global Fund to provide up to 2 million doses of lenacapavir at no profit in LLMICs. This agreement was designed to bridge access until generic manufacturers under voluntary licensing arrangements could meet demand across 120 high-incidence countries. Distribution will be prioritized according to national HIV prevention strategies, while Gilead has contracted at-risk manufacturing capacity to ensure supply.4
References
1.Patel RR, Hoover KW, Lale A, Cabrales J, Byrd KM, Kourtis AP. Clinical Recommendation for the Use of Injectable Lenacapavir as HIV Preexposure Prophylaxis — United States, 2025. MMWR Morb Mortal Wkly Rep 2025;74:541–549. DOI: http://dx.doi.org/10.15585/mmwr.mm7435a1
2.Gilead Sciences. Gilead announces partnership with PEPFAR to deliver twice-yearly lenacapavir for HIV prevention. Business Wire. Published September 18, 2025. Accessed September 6, 2025. https://www.gilead.com/news/news-details/2025/gilead-announces-partnership-with-pepfar-to-deliver-twice-yearly-lenacapavir-for-hiv-prevention-for-up-to-two-million-people-in-primarily-low--and-lower-middle-income-countries
3. Gilead. Yeztugo® (Lenacapavir) Is Now the First and Only FDA-Approved HIV Prevention Option Offering 6 Months of Protection. June 18, 2025. Accessed September 18, 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
4.Gilead Finalizes Agreement With the Global Fund to Accelerate Access to Twice Yearly Lenacapavir for HIV Prevention for up to Two Million People in Primarily Low and Lower Middle Income Countries. Gilead.com. Published 2025. Accessed September 18, 2025. https://www.gilead.com/news/news-details/2025/gilead-finalizes-agreement-with-the-global-fund-to-accelerate-access-to-twice-yearly-lenacapavir-for-hiv-prevention-for-up-to-two-million-people-in-primarily-low--and-lower-middle-income-countries
