HIV Infections Did Not Appear Among Young Women Given a Twice-Yearly Injection

CATEGORY: DISEASE PREVENTION

Among 2,134 young women given a twice-yearly injection, not one infection occurred. Among 2,179 men and gender-diverse adults given the same injection, there were two.¹² Those are the HIV results of two large international trials of a drug called lenacapavir. HIV, the human immunodeficiency virus, attacks the body’s immune defenses and causes AIDS if untreated. It still infects more than a million people worldwide each year.

Six Months of Protection From One Shot Under the Skin

Daily prevention pills, known as PrEP, work very well when taken consistently. The full name is pre-exposure prophylaxis: medicine taken in advance so the virus cannot take hold. Consistency is the weak link. A pill has to be remembered every day, for years on end. Lenacapavir takes a different route. It disables the virus’s capsid, the protein shell that guards its genetic material, and it is long-acting. One injection under the skin of the abdomen keeps working for six months, like a smoke detector whose battery needs changing twice a year.

Neither the Volunteers Nor the Researchers Knew Who Got the Shot

The first trial enrolled 5,338 adolescent girls and young women in South Africa and Uganda; the second enrolled 3,265 cisgender men, transgender women and men, and nonbinary people across seven countries. Both were randomized and double-blind. Who received the injection and who received a daily prevention pill was settled at random, and nobody on either side of the needle knew which. Everyone was tested for HIV at regular visits. New infections in each group were then measured against the infection rate in the broader screened population, which stands in for the rate expected with no added protection.

Zero Infections Against 55 on Daily Pills

In the women’s trial, zero infections occurred among the 2,134 participants receiving lenacapavir, while 55 occurred among the 3,204 assigned to daily pills.¹ In the men’s and gender-diverse trial, two infections occurred among 2,179 lenacapavir recipients, which was 96% below the background rate and 89% below the rate in the daily-pill group.² The pills’ weaker showing came down largely to adherence, since blood testing showed many participants were not taking them regularly. In the women’s trial, the F/TAF daily pill showed no clear reduction in infections compared with the expected background rate.¹

Nodules, Gilead Money, and an Earlier Injection

The drug forms a small deposit under the skin that can be felt as a nodule, and injection-site reactions were the most common side effect. About 1% of injection recipients in the second trial stopped for that reason. Gilead Sciences, which makes the drug, funded both trials, which is standard practice for a new medicine. American regulators approved the injection, sold as Yeztugo, for HIV prevention in June 2025.

Lenacapavir is not the first long-acting injection tested against daily pills. In an earlier randomized trial of 4,566 men and transgender women, cabotegravir, given every two months, was linked to 66% fewer HIV infections than daily prevention pills.³ The margin there is smaller than lenacapavir’s. The direction is the same: in randomized comparisons, injections spaced months apart have come out ahead of pills that must be taken daily.

Key Takeaways

• A twice-yearly lenacapavir injection was followed by zero HIV infections among 2,134 women and two among 2,179 men and gender-diverse adults, across two randomized trials.
• That infection rate ran 96% below the expected background rate and 89% below the rate on a daily prevention pill, which many participants were not taking regularly.
• Both trials were randomized and blinded, which makes the evidence strong, though injection-site nodules were common and the drug’s manufacturer paid for the work.
• Regulators approved the injection for HIV prevention in the United States in June 2025.

References

1. Bekker LG, Das M, Abdool Karim Q, et al. Twice-Yearly Lenacapavir or Daily F/TAF for HIV Prevention in Cisgender Women. The New England Journal of Medicine. 2024;391(13):1179–1192. link
2. Kelley CF, Acevedo-Quiñones M, Agwu AL, et al. Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons. The New England Journal of Medicine. 2025;392(13):1261–1276. link
3. Landovitz RJ, Donnell D, Clement ME, et al. Cabotegravir for HIV prevention in cisgender men and transgender women. The New England Journal of Medicine. 2021;385(7):595–608. link.