Goats and Soda: NPR

For more than a decade, taking a pill like Truvada every day has been the standard treatment for HIV prevention.

In clinical trials, this type of preventive medicine, called pre-exposure prophylaxis (PrEP), can be 99% effective at stopping new HIV infections from happening through sex. In the real world, that’s not always the case.

People don’t always take their pills. In a study in South Africa, women said they felt there was a stigma attached to the pill — a sexual partner might assume they are taking the pill because they already have HIV or because they have other partners.

Now, a new trial — called PURPOSE 1 — is pointing the way to a new preventive strategy — a twice-yearly injection of a drug called lenacapavir. The trial was sponsored by Gilead Sciences, the California-based maker of the drug.

In this double-blind, randomized study of 5,300 cisgender women in South Africa and Uganda, 2,134 got the shot and the rest took one of two types of daily PrEP pills. The trial began in August 2021, and so far, no woman who got the shots has contracted HIV. Participants who got one of the oral PrEP options, Truvada and Descovy, had infection rates of about 2% — consistent with infection rates for oral PrEP in other clinical trials.

These results were significant enough for the Data Monitoring Committee — an independent group of experts appointed to review the progress of clinical trials — to recommend that Gilead stop its blinded trial and offer lenacapavir to all trial participants. On June 20, Gilead announced these results, and now all participants can choose to receive the injection.

The study’s focus on women in sub-Saharan Africa is based on HIV data. Despite making up 10% of the world’s population, sub-Saharan Africans account for two-thirds of those living with HIV – 25.7 million out of 38.4 million. And every week, around 4,000 teenage girls and young women in Africa are newly infected with HIV.

The first reaction is positive

The study still needs to be peer-reviewed, but initial results have been received with enthusiasm.

“It’s fantastic,” says Dr. Jason Zucker, an assistant professor of medicine and infectious disease expert at Columbia University Vagelos College of Physicians and Surgeons. “It’s hard to take a drug every day. A drug that [given] every 6 months has a lot of potential.”

Dr. Philip Grant, clinical associate professor and director of the HIV clinic at Stanford University School of Medicine, agrees that lenacapvir could help fill a gap in prevention options. “It would be a great benefit for populations with adherence issues,” he says.

Despite being 99% effective in some studies, the effectiveness of oral PrEP drops significantly in practice. One study found that PrEP was only 26% effective in certain populations, such as men under 30.

“Medication works if you take it,” Zucker says. “A medication that’s given every six months has a lot of potential, because if you can get checked twice a year, you’re essentially protected for 12 months.”

Advocacy groups have also expressed excitement about the preliminary results of lenacapavir as a PrEP option. “Lenacapavir would be ‘a real game-changer,’ particularly for people who face stigma and discrimination in low- and middle-income countries,” said a statement from the People’s Medicines Alliance — a global coalition of more than 100 organizations covering 33 countries that advocate for greater access to medicines.

The drug is not new; its use is

Lenacapavir is not a new drug. It has been approved by the FDA in the United States for multi-drug resistant HIV therapy since 2022. But GOAL 1 is the first clinical trial to test it on HIV prevention.

The PURPOSE 1 study is part of a larger initiative to improve HIV prevention in the Global South. It is one of several studies that are part of the ongoing effort to end the HIV epidemic by 2030.

An ongoing PURPOSE 2 study is analyzing the efficacy of lenacapavir among cisgender men, transgender men, transgender women, and nonbinary people who have sex with partners assigned male at birth in Argentina, Brazil, Mexico, Peru, South Africa, Thailand, and the United States.

Any eventual approval and widespread use would come with challenges. According to an analysis presented at the 24th International AIDS Conference (AIDS 2022), PrEP drugs would have to cost less than $54 per year per patient for South Africa, for example, to afford them. Lenacapavir as an HIV treatment in the United States in 2023 was $42,250 per new patient per year. Oral PrEP options, by contrast, can cost less than $4 per month.

“The biggest gap in prevention is not medications, it’s access to medications,” says Dr. Grant.

Activists across Uganda and South Africa[MIG5] have urged Gilead Sciences to license lenacapavir to the Medicines Patent Pool — a United Nations-backed organization that works with governments, industry and others to license medicines. This would allow generic versions of the drug to be produced at a fraction of the cost.

These activists fear that history will repeat itself: In 2021, cabotegravir, a long-acting injectable PrEP drug produced by ViiV Healthcare, was approved by the FDA. The drug is more effective than oral options and only requires 2 injections every 2 months. But despite approval for generic versions of the drug, these versions must still go through the World Health Organization’s review process to show that they are as effective as the brand-name version. Because this process takes time, generic cabotegravir likely won’t be available in Africa until 2027.

Since sharing the early success of lenacapavir, Gilead has announced that they plan to “supply lenacapavir rapidly, sustainably, and in sufficient volumes, if approved, to high-incidence, resource-limited countries.” Their access strategy involves developing a voluntary licensing program that would allow generic versions to be produced before the original patent expires. When NPR asked Dr. Jared Baeten, Gilead’s vice president of HIV Clinical Development, about timelines, he said estimates will depend on “another trial, regulatory review, and approval.”

“Cost is going to be a big factor here,” says Dr. Zucker. “I think and hope that we’re going to do everything we can to reduce the barriers to access.”