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

CATEGORY: DISEASE PREVENTION

An injection given just twice a year was linked to near-total protection against HIV in two large international trials: among 2,134 young women who received it, not a single infection occurred, and among 2,179 men and gender-diverse adults, there were just two.¹² HIV—the human immunodeficiency virus, which attacks the body’s immune defenses and causes AIDS if untreated—still infects more than a million people worldwide each year.

Lenacapavir Disables the Virus Capsid for Six Months

Daily prevention pills, known as PrEP—pre-exposure prophylaxis, medicine taken in advance so the virus cannot take hold—work very well when taken consistently. Consistency is the weak link: a pill must be remembered every day, for years. The injected drug, lenacapavir, takes a different approach. It disables the virus’s capsid—the protein shell that protects 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 only needs changing twice a year.

5,338 Young Women in South Africa and Uganda

Both trials were randomized and double-blind—participants were assigned by chance to the injection or to a daily prevention pill, and neither they nor the researchers knew who received which. The first 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 in seven countries. Everyone was tested for HIV at regular visits, and new infections in each group were compared with the infection rate among the broader screened population—the rate expected with no added protection.

Zero Infections Versus 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—96% below the background rate, and 89% below the rate in the daily-pill group.² The daily pills’ weaker showing was largely a matter of adherence: 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

About 1% Stopped Over Injection Site Reactions

Injection-site reactions were the most common side effect—the drug forms a small deposit under the skin that can be felt as a nodule—and about 1% of injection recipients in the second trial stopped for that reason. Both trials were funded by Gilead Sciences, the drug’s maker, a routine arrangement in drug trials. U.S. regulators approved the injection, sold as Yeztugo, for HIV prevention in June 2025.

Cabotegravir Linked to 66% Fewer Infections Than Pills

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—an injection given every two months—was linked to 66% fewer HIV infections than daily prevention pills.³ That is a smaller margin than lenacapavir’s, but it points the same way: in randomized comparisons, injections given every few months have been linked to fewer infections than pills that must be taken daily.

Key Takeaways

• In two large randomized trials, a twice-yearly lenacapavir injection was linked to zero HIV infections among 2,134 women and two among 2,179 men and gender-diverse adults.
• The injection’s infection rate was 96% below the expected background rate and 89% below that of a daily prevention pill, largely because daily pills are often not taken consistently.
• Because participants were randomly assigned and blinded, this is strong evidence—though injection-site nodules were common, and the trials were funded by the drug’s manufacturer.
• The injection was approved 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.