A new way to prevent HIV infection is generating great buzz -- and more than a bit of controversy -- at this week’s AIDS 2024 Conference in Munich.
The treatment consists of a twice-yearly injection of a drug called lenacapavir.
Early trial results were released in June and generated great excitement, indicating 100% efficacy. On Wednesday, July 24, the full peer-reviewed results were released at the AIDS 2024 conference, confirming the preliminary data.
The trial was sponsored by Gilead Sciences, the California-based maker of the drug.
This treatment offers an alternative to the current standard of core for HIV prevention efforts for over a decade: taking a pill like Truvada every day.
In clinical trials, this type of preventive drug, called pre-exposure prophylaxis (PrEP), can be 99% effective in stopping new HIV infections from sex. In the real world, however, that is 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 to the pill -- a sexual partner might assume they’re taking it because they already have HIV or because they have other partners.
The new trial results, released on Wednesday, point the way to a new preventive strategy.
In a double-blind, randomized study of 5,300 cisgender women in South Africa and Uganda, 2,134 got the injection and the others took one of two types of daily PrEP pills. The trial began on August 2021 and, so far, not a single woman who received the injections has contracted HIV. The participants who received either of the oral PrEP options, Truvada and Descovy, had infection rates of about 2% -- consistent with the infection rates of oral PrEP in other clinical trials.
These results were significant enough for the Data Monitoring Committee -- an independent group of experts appointed to assess the progress of clinical trials -- to recommend that Gilead halt its blinded trial and offer lenacapavir to all study 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 accounting for 10% of the world’s population, sub-Saharan Africans comprise two-thirds of people living with HIV -- 25.7 million out of 38.4 million. And, every week, about 4,000 teen girls and young women in Africa are newly infected with HIV.
An enthusiastic response
When the early results were announced, there was a groundswell of 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 medication every single day. A medication that is [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 big benefit in populations that have adherence challenges,” he says.
Despite being 99% effective in some trials, oral PrEP effectiveness drops significantly in the real-world. One study showed PrEP effectiveness to be as low as 26% in certain populations -- men under age 30, for example.
The PURPOSE 1 data published today in the New England Journal of Medicine showed that adherence to the oral medications in the study was low -- meaning that, in the 10% sample of women for which drug levels were measured, most took fewer than 2 tablets per week. But the better the adherence, the fewer the HIV infection rates. Lenacapavir injections, on the other hand, were administered on time to about 92% of participants.
“Medications work when you take them,” says Zucker. “A medication that is given every six months has a lot of potential because, essentially, if you can make two visits a year, you are protected for an entire 12 months.”
Advocacy groups have also expressed enthusiasm about lenacapavir’s preliminary results as a PrEP option. “Lenacapavir would be “a real game-changer,” particularly for people facing stigma and discrimination in low- and middle-income countries,” read a statement by People’s Medicines Alliance -- a global coalition of more than 100 organizations that span 33 countries and that advocate for making medications more accessible.
More trials ahead
Lenacapavir is not a new drug. It’s been approved by the FDA in the United States for multi-drug resistant HIV treatment since 2022. But PURPOSE 1 is the first clinical trial to test it for HIV prevention.
The PURPOSE 1 trial is part of a larger initiative to improve HIV prevention across the global south. It is one of several studies that are part of ongoing efforts to end the HIV epidemic by 2030.
An ongoing PURPOSE 2 trial is analyzing lenacapavir’s efficacy among cisgender men, transgender men, transgender women and non-binary individuals 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 medications would need to cost less than $54 a year per patient for South Africa, for example, to afford them. Lenacapavir’s cost as HIV treatment in the United States in 2023 was $42,250 per new patient per year. Oral PrEP options, on the other hand, can cost less than $4 a month.
“The biggest gap in prevention isn’t medication, it’s accessing medications,” says Dr. Grant.
Activists across Uganda and South Africa have urged Gilead Sciences to license lenacapavir to the Medicines Patent Pool -- a United Nations-backed organization that partners with governments, industry and other organizations to license medications. This would allow for manufacturing of generic versions of the drug at a fraction of the cost.
These activists fear that history will repeat itself: In 2021, cabotegravir. a long-acting injectable PrEP medication manufactured by ViiV Healthcare, was FDA-approved. The medication is more effective than oral options and only requires one injection every two months after the initiation period. But despite approval for generic versions of the medication, these versions still have to go through the World Health Organization review process to show they are equally effective to the brand version. Because this process takes time, generic cabotegravir will likely not be available in Africa until 2027.
Since sharing lenacapavir’s early success, Gilead has announced that they intend to “deliver lenacapavir swiftly, sustainably and in sufficient volumes, if approved, to high-incidence, resource-limited countries.” Their access strategy includes developing a voluntary licensing program that would enable 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 timeframes, he said that estimates will depend on "another trial, a regulatory review and approval."
The matter of pricing
“Cost is going to play into this dramatically,” says Dr. Zucker, “I think and hope we will do everything we can to try to reduce barriers to access.”
A new analysis released at AIDS 2024 on July 23 has shown that the price for injectable lenacapavir could be reduced to as low as $26 to $40 per patient per year -- one thousand times less than its current price in the U.S. But this would only be possible through voluntary license agreements allowing for generic versions to be made, and with competition among companies to produce the generic drug at the cheapest price tag.
In response to these new cost estimates, a group of MSF activists gathered at AIDS 2024 and called for an “immediate global action to break Gilead’s monopoly on lenacapavir.”
NPR reached out to Gilead for comment. A spokesperson responded by email that “the results of PURPOSE 2 are required for regulatory filing, and lenacapavir for HIV prevention remains an investigational drug until approved by regulatory authorities. While Gilead awaits the results of this Phase 3 clinical trial and the potential FDA filing, it is too early to state the price of lenacapavir for HIV prevention. Gilead is committed to access pricing for high-incidence, resource-limited countries. The current price for the approved indication in the heavily treated HIV population will not be our reference.”
The company’s full response can be found in its “Updated Statement on Global Access Planning.”
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