Twice-yearly injections of lenacapavir for HIV prevention provided nearly complete protection in two large trials. No new infections occurred among cisgender women, and only one case appeared in a study involving cisgender men and gender-diverse individuals.
The results emerged from open-label extensions of the PURPOSE 1 and PURPOSE 2 trials, shared at the 26th International AIDS Conference in Rio de Janeiro. Earlier phases had already shown the drug’s effectiveness, but the new findings strengthen its role as a long-acting option compared to daily oral pre-exposure prophylaxis (PrEP).
High adherence, no new safety concerns
Participants largely followed the injection schedule. In PURPOSE 1, which enrolled cisgender women, 96% received their second dose at week 52. The second trial, which enrolled cisgender men and gender-diverse individuals, reported 96% adherence at week 26 and 92% at week 52.
Noah Kiwanuka, an associate professor at Makerere University in Uganda and lead author of the PURPOSE 1 results, stated the extension revealed no additional safety issues. Marcelo Losso, who presented PURPOSE 2 data, confirmed the drug’s safety profile matched earlier observations.
The sole infection in PURPOSE 1 involved a participant who switched from lenacapavir to daily oral PrEP (emtricitabine/tenofovir disoproxil fumarate). In PURPOSE 2, one infection happened during the open-label extension.
Supply shortages limit global rollout
The drug’s availability remains restricted in some high-burden countries despite the positive data. Zambia, where HIV prevalence ranks among the highest globally, has rationed lenacapavir to select sites and individuals already receiving reinjections. Lloyd Mulenga, director of infectious diseases at Zambia’s Ministry of Health, said the country awaits 60,000 to 80,000 doses promised by the U.S. government.
The Global Fund to Fight AIDS, Tuberculosis and Malaria announced in April that it and the U.S. would increase their lenacapavir PrEP target from 2 million to 3 million people by 2028. Advocates argue the goal falls short. Mitchell Warren, executive director of the U.S.-based group AVAC, called the target progress but inadequate.
“The commitment was too small,” Warren said. “We should aim for 5 million people annually within the next three to five years.” He noted that scaling production could eventually lower the drug’s cost below that of oral PrEP.
At a press conference, Winnie Byanyima, executive director of UNAIDS, described lenacapavir and similar long-acting methods as nearly as effective as a vaccine. She pointed out that 20 million people could benefit if global efforts speed up.
Lenacapavir’s potential has drawn comparisons to a functional HIV vaccine, a long-sought goal. When initial trial results appeared at the 2024 conference, they were seen as a major shift in HIV prevention. A science publication later named it the 2024 Breakthrough of the Year.
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The gap between scientific success and real-world access remains significant. While the latest data confirm the drug’s safety and effectiveness, manufacturing constraints and funding issues have slowed its rollout. Beatriz Grinsztejn, president of the International AIDS Society, which organizes the conference, called the results “an extraordinary advance” but emphasized the need to reach those most at risk.
“Efforts must accelerate to deliver this advance to those who need it most,” she said.
The manufacturer, Gilead Sciences, has faced criticism over pricing and distribution, especially in low- and middle-income countries. The company has committed to offering lenacapavir at a reduced cost in high-burden regions, but negotiations with governments and health organizations continue.
For many who could benefit, the injections remain unavailable. In sub-Saharan Africa, where nearly two-thirds of new HIV infections occur, limited supply has forced tough decisions about distribution.
The conference runs through Friday, with more data on HIV prevention strategies expected soon.
