A pharmacist holds a vial of lenacapavir at the Desmond Tutu Health Foundation's Masiphumelele Research Site in Cape Town, South Africa. The development of the drug has been hailed as a 2024 breakthrough by the journal Science, which described it as "a significant step towards reducing HIV/AIDS as a global health emergency."
Can we end the HIV epidemic?
This question has been debated since the beginning of the epidemic in the 1980s. With 1.3 million new infections each year, the epidemic continues to rage ... and the world is not on track to meet the ambitious U.N. goal of ending HIV/AIDS by 2030.
But in 2024, results from two groundbreaking clinical trials of a drug called lenacapavir showed that it can virtually eliminate new HIV infections through sex, raising hopes among infectious disease experts.
The emerging data on lenacapavir is so striking that the drug’s development has been hailed as a 2024 breakthrough by the journal Science, which described it as “a significant step toward reducing HIV/AIDS as a global health emergency.”
Newly released results from Purpose 2, a clinical trial sponsored by California-based lenacapavir manufacturer Gilead Sciences, found that the drug was 96% effective in preventing HIV infection in more than 3,200 cisgender men, transgender men, transgender women and gender non-binary people who had sex with partners assigned male at birth. The study was conducted at various sites in Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States.
The results follow similarly dramatic findings from an earlier lenacapavir trial called Purpose 1, which included 5,300 cisgender women in South Africa and Uganda. Headlining the AIDS 2024 conference in Munich in July, early results showed 100% efficacy, while Gilead Sciences announced that not a single woman who received the drug has developed HIV since the trial began in August 2021.
As recognized by science, lenacapavir was developed through years of research into the structure and function of HIV’s capsid protein, which protects the virus’s genetic material. Lenacapavir’s remarkable ability to prevent HIV transmission is based on its ability to rigidify this protein, which blocks key steps in viral replication.
Ethel Weld, an assistant professor at the Johns Hopkins University School of Medicine, described the results of the Aim 1 and Aim 2 trials as “an exciting game changer for HIV prevention.”
Alternative to daily pills
In particular, lenacapavir, which is given by injection twice a year, represents a dramatic new alternative to the current standard of care for HIV prevention: taking a pill called Truvada every day. While this type of medication, called pre-exposure prophylaxis (PrEP), has also been shown to be 99% effective in preventing HIV infection from sex in clinical trials, this is not necessarily the case in the real world.
People don’t always take their pills. In a study in South Africa, women said they felt stigma around the pill – that sexual partners might assume they were taking it because they already had HIV or because they had other partners. The research also highlighted significant barriers to taking daily oral PrEP among men who have sex with men, including the drug’s availability, inconvenience, and perceptions that it was unnecessary. One study showed that in certain populations — for example, men under 30 — oral PrEP was as effective as 26%.
Sponsor Messageweld points out that in both the Aim 1 and Aim 2 trials, it was notable that participants randomized to receive daily oral PrEP instead of lenacapavir showed lower adherence to the medication.
“The burden of taking medication every day varies from person to person and may be more burdensome for healthy people who feel well,” says Weld. “The discovery that twice-yearly injections are so effective at preventing HIV reduces the amount of time a person has to protect themselves for the rest of their lives. It brings lenacapavir very close to the realm of other preventive paradigms, such as vaccination.”
A potential ‘game-changer’
Advocacy groups have also expressed great enthusiasm. “Lenacapavir will be a “real game-changer”, especially for people facing stigma and discrimination in low- and middle-income countries,” read a statement from the People’s Medicine Alliance – a global coalition of more than 100 organizations spread across 33 countries and advocating for making the drugs more accessible.
HIV researcher Cecile Tremblay of the University of Montreal highlighted the drug’s potential to tackle the epidemic in sub-Saharan Africa, where the burden of the disease is highest. Despite making up 10% of the world’s population, sub-Saharan Africans account for two-thirds of people living with HIV – 25.7 million out of 38.4 million. Every week, about 4,000 adolescent girls and young women in Africa are newly infected with HIV.
“Not only is lenacapavir highly effective, but it has been shown to be effective in the female population in sub-Saharan Africa where the epidemic is highest, and oral PrEP has not performed well due to stigma and discrimination,” Tremblay says.
Next steps
Lenacapavir is not a new drug. It has been approved by the FDA in the United States for the treatment of multi-drug resistant HIV since 2022. But Aim 1 and Aim 2 are the first clinical trials to test it for HIV prevention.
According to Gilead Sciences, data from the two trials will now be used to support a series of global regulatory filings that will begin by the end of 2024, with the aim of launching lenacapavir on the market in 2025.
Yet any final approval and widespread use will come with challenges. According to an analysis presented at the 24th International AIDS Conference (AIDS 2022), for South Africans, PrEP drugs should cost less than $54 per patient per year to be affordable. Lenacapavir cost $42,250 per year as an HIV treatment in the United States in 2023. On the other hand, oral PrEP options can cost as little as $4 per month.
Given the drug’s potential, Tremblay says it’s important to have as broad an access as possible.
“There needs to be infrastructure to reach people at risk and make sure they can access it,” she says. “If everyone at risk can get this prophylaxis, it can change the trajectory of the epidemic within a few years. When you significantly reduce transmission rates, the epidemic can be reduced.”
Professor Linda-Gail Baker, director of the Desmond Tutu HIV Centre at the University of Cape Town, wholeheartedly agrees. "While we wait for generic companies [to create generic forms of lenacapavir], I think where trials of lenacapavir have been conducted, there should be access from the company that started this product or, in the future, from generics companies. We cannot have a world where this miracle is not in the hands of the people who contributed to it."
But in 2024, results from two groundbreaking clinical trials of a drug called lenacapavir showed that it can virtually eliminate new HIV infections through sex, raising hopes among infectious disease experts.
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