Men Given a Twice-Yearly Injection Were Protected From HIV

CATEGORY: DISEASE PREVENTION

An injection given just twice a year prevented nearly every expected HIV infection in an international trial of 3,265 people. Two participants receiving lenacapavir acquired HIV over the follow-up period, an infection rate 96% below what researchers calculated would have occurred with no preventive medicine at all, and 89% below the rate in participants taking the standard daily prevention pill.¹

The Daily Pill’s Weak Spot Is the Word Daily

Preventive HIV medication, known as PrEP, short for pre-exposure prophylaxis, has existed as a daily pill for over a decade, and it works remarkably well when taken consistently. There’s the catch. Protection depends on a pill every day, indefinitely, and in real life doses get missed, prescriptions lapse, and some people avoid pills that might be spotted by family or partners. Lenacapavir attacks that weak spot with pharmacology. It’s a long-acting antiviral, injected under the skin of the abdomen, that keeps working for six months. The drug blocks the protein shell the virus needs to copy itself, a target no earlier prevention medicine used. Two clinic visits a year replace 365 daily decisions. Nothing comes home in a bottle.¹

Seven Countries, Two Real Drugs, No One the Wiser

The trial enrolled HIV-negative cisgender men, transgender women, transgender men, and nonbinary adults across seven countries, all with exposure that put them at real risk. A blinded randomization gave two-thirds the twice-yearly injection and one-third the established daily pill, with dummy versions of each so nobody knew their group. The yardstick was something cleverer than a placebo. Daily PrEP already works, so giving anyone a sugar pill would have been unethical. Instead, the researchers tested people screened for the trial in these same communities to estimate the background infection rate, meaning the rate among people using no preventive medicine at all. Each arm of the trial was then measured against that estimate.¹

Two Infections Among More Than Two Thousand People

Among 2,177 people on lenacapavir, there were 2 infections. That works out to 0.10 per 100 per year, or about one infection per thousand people per year. Among 1,088 on the daily pill, there were 9, a rate of 0.93 per 100. Both approaches beat the background estimate decisively. The injection also beat the pill itself, by 89%. The main price was paid at the injection site. Lumps and irritation under the skin were common, and 26 of the roughly 2,180 injected participants quit the study over them. No new safety concerns emerged, and the researchers reported the drug was otherwise well tolerated.¹

Approved, Recommended, and Matched in Women

This result didn’t stand by itself for long. A companion trial in more than 5,000 young women in South Africa and Uganda had already reported zero HIV infections among those receiving the same twice-yearly injection.² On the strength of the pair, the FDA approved lenacapavir for HIV prevention in June 2025. The CDC followed with a formal recommendation covering adults and adolescents who could benefit from PrEP, grading the supporting evidence as high certainty.³ For the many people who qualify for preventive medication but never start it, or start and drift off, a twice-yearly option changes what staying protected asks of them. Whether that convenience translates into fewer infections at the population level is the question the coming years will answer. Cost and insurance coverage will shape the answer as much as the pharmacology does.

Key Takeaways

• Twice-yearly lenacapavir injections left HIV incidence 96% below the expected background rate and 89% below the daily-pill group: 2 infections among 2,177 people versus 9 among 1,088.
• Injection-site lumps and irritation were the main side effect, enough that 26 participants stopped.
• Lenacapavir is now FDA-approved for prevention and carries a CDC recommendation, making it the first HIV prevention option that asks for just two decisions a year.

References

1. Kelley CF, Acevedo-Quiñones M, Agwu AL, et al. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. New England Journal of Medicine. 2025;392(13):1261–1276. link
2. Bekker LG, Das M, Abdool Karim Q, et al. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. New England Journal of Medicine. 2024;391(13):1179–1192. link
3. 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 Morbidity and Mortality Weekly Report. 2025;74:541–549. link