A global study shows a twice-yearly injection can prevent HIV and is a more practical option than a daily pill

By Clara Silvestri

A major global study, published in the New England Journal of Medicine in November 2024, has revealed a powerful new tool in the fight against human immunodeficiency virus (HIV). The tool is an injectable medication called lenacapavir, and it may redefine how HIV is prevented. Lenacapavir falls under the category of pre-exposure prophylaxis (PrEP), a medication taken by HIV-negative people to prevent the replication of the virus in the body.

Oral PrEP is the most commonly prescribed medication for preventing HIV, where in people take a pill daily. While oral PrEP is 99 percent effective in preventing new infections, it remains widely underused, with an estimated eight million people taking it worldwide compared to the United Nations’ goal of 21.2 million users. With 1.3 million new HIV diagnoses in 2024 alone, the need for preventing even more infections is critical. Lenacapavir, unlike the pill, is transformative as it needs to be injected twice a year instead of being taken daily.

“About half of the people who start taking oral PrEP stop within the first year of starting it,” says Colleen Kelley, a physician and professor at Emory University School of Medicine and the senior author on the study. “It’s a lot easier for people to incorporate these long-acting injectables into their lifestyle than it is for them to take a medication every day.”

The lenacapavir injection offers a simpler medication schedule for those who may struggle with taking a pill every day. There is still stigma associated with taking daily PrEP, and many people at risk for HIV may lead unpredictable lives that are not compatible with a strict medication schedule.

Kelley led the large team of global collaborators on the trial. The team established 92 different trial sites across the United States, Brazil, Thailand, South Africa, Peru, Argentina, and Mexico to properly represent populations disproportionately affected by HIV. Over 99 percent of the people selected for the trial engaged in high-risk HIV infection behaviors such as unprotected sex and injection drug use.

The trial participants were all routinely tested for HIV while either taking a daily PrEP pill or receiving twice-yearly lenacapavir injections. Of the 1,086 participants on the daily PrEP regimen, nine tested positive for HIV. Of the 2,179 participants on the lenacapavir regimen, only two tested positive for HIV. Though infection rates were low across both groups, lenacapavir was still more effective than oral PrEP in preventing HIV.

HIV remains a major global public health concern since the beginning of the epidemic in 1981, despite the significant decrease in diagnoses per year. If implemented globally, lenacapavir could be a serious game-changer for preventing new HIV infections, especially in populations where oral PrEP adherence is low.

Lenacapavir’s broad success across gender-diverse populations is a key driver in its potential for global implementation. The drug has already been shown to be effective in preventing HIV infections in cisgender women, and this trial expands its results to cisgender men, transgender men and women, and non-binary people. “If we’re successfully able to roll out lenacapavir to everyone who needs it, we will see stark decreases in new HIV infections,” says Kelley.

The rollout of lenacapavir has already begun. Dylan Baker, a physician and assistant professor at Emory University School of Medicine, is currently integrating it into his HIV clinic. A main concern of Baker’s is the equitable implementation of this expensive medication.

“You have to do a lot of work up front to make sure that the medication is going to get paid for and the patients don’t end up with a large bill at the end of the day,” says Baker. “We aim for all of our PrEP drugs to be 100 percent free for all of our patients, insured or uninsured.”

Lenacapavir is not the only form of injectable PrEP available for HIV prevention. Baker has previously studied cabotegravir, an injectable first approved for use in the United States in 2021. Like lenacapavir, Baker’s study also found that cabotegravir was more effective than oral PrEP in preventing new HIV infections. However, cabotegravir must be injected once every two months, compared with lenacapavir’s twice-yearly schedule.

The appeal of lenacapavir cannot be overstated. It could be the difference between HIV prevention methods that work in controlled studies and HIV prevention methods that work in the real world. An easy and discreet medication gives people more of an incentive to adhere to it and therefore ensure their protection against HIV. Lenacapavir could be a key player in ending the HIV epidemic in the future, but it will likely not be the only player.

Lenacapavir adds a practical new option to the existing toolbox of HIV prevention strategies. The expansion of these strategies provides people who are at risk for HIV with more prevention options to choose from. Finding the specific medication that works best for someone as an individual is a crucial first step in decreasing HIV infections at the population level.

“The only HIV prevention option that is going to work is the one that people actually use,” says Kelley. “Our hope is that one day you can just go to the pharmacy and choose whatever intervention is best for you.”