Twice-yearly injectable lenacapavir has continued to demonstrate exceptional protection against HIV infection.
Twice-yearly injectable lenacapavir continued to provide strong protection against HIV in two landmark clinical trials, with updated data showing almost no new infections, high adherence and no new safety concerns. Researchers said updated findings from the PURPOSE-1 and PURPOSE-2 studies showed the long-acting drug remained highly effective, safe and well accepted by participants during extended follow-up. This raises hope that the long-acting drug could transform HIV prevention if rolled out equitably.
Injectable lenacapavir is a highly effective long-acting form of pre-exposure prophylaxis (PrEP) that can be administered just twice a year and has shown near-complete effectiveness in preventing HIV infection, making it a potentially transformative HIV prevention medicine.
“Lenacapavir for HIV prevention is a breakthrough advance with the potential to accelerate global prevention progress if it is delivered rapidly and equitably,” said Beatriz Grinsztejn, the director of the HIV/AIDS Clinical Research Unit at Fiocruz in Brazil. She is also a member of the PURPOSE-2 study team.
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Grinsztejn said that the injectable prevention drug has already been approved by regulators in many parts of the world and that global rollout has begun.
The updated findings presented at the AIDS 2026 conference build on earlier results that established lenacapavir as one of the most effective HIV prevention tools ever studied. Researchers say the latest data further strengthens the case for rapid and equitable global rollout.
Zero HIV infections among women
The PURPOSE-1 trial enrolled cisgender women in South Africa and Uganda. During the earlier randomized, blinded phase, twice-yearly lenacapavir demonstrated superior protection against HIV compared with daily oral PrEP. After that phase concluded, participants were offered the chance to receive lenacapavir in an open-label extension – an offer more than 95% of them accepted.
Dr Noah Kiwanuka of the Makerere University School of Public Health said the latest analysis examined whether twice-yearly subcutaneous lenacapavir remained effective and well tolerated over a longer follow-up period after participants were given the choice to receive the injectable drug.
“We found no new infections in the first 52 weeks of the open-label extension, both in those who continued with the lenacapavir and those who switched from oral PrEP,” Kiwanuka said.
He said the absence of new HIV infections during the first year of the extension showed that the drug’s high level of protection was maintained over time.
“Given that no new infections were seen in the first 52 weeks of the open-label extension phase, the efficacy of lenacapavir remains high during this time of follow-up,” he said.
Researchers also found that lenacapavir remained safe and well tolerated, with similar safety outcomes among participants who switched from oral PrEP and those who continued receiving the injections.
Kiwanuka said adherence to the twice-yearly injections remained exceptionally high throughout the extension phase, exceeding 97% among participants who switched from oral PrEP and more than 94% among those who had already been receiving lenacapavir.
“The drug is safe and well tolerated between those who switched from oral PrEP to lenacapavir and those who continued with lenacapavir,” he said.
Taken together, Kiwanuka said the findings reinforce lenacapavir’s potential as a long-acting HIV prevention option for women.
“These findings taken together show that lenacapavir still has a high efficacy in the open-label phase, and this, in combination with a consistent safety and durability profile, reinforces lenacapavir as a transformative PrEP option for cisgender women,” he said.
Grinsztejn reported that just one HIV acquisition occurred in a participant who was on blinded lenacapavir, and one additional acquisition occurred in a participant after they had switched from blinded lenacapavir to open-label oral PrEP.
Adherence to the twice-yearly injection schedule was very high, said Grinsztejn, reaching 96% at week 52 of the open-label extension, “and no new safety concerns were identified.”
Strong protection continues across diverse populations
The second data set comes from PURPOSE-2, which enrolled cisgender men and gender-diverse individuals across Argentina, Brazil, Mexico, Peru, South Africa, Thailand and the United States.
Dr Marcelo Losso, from the Hospital General de Agudos José María Ramos Mejía in Buenos Aires, Argentina, said that PURPOSE-2 is built on the trial’s earlier findings, which showed that lenacapavir was highly effective at preventing HIV infection during the randomized, blinded phase of the study.
After that phase ended, participants could either continue receiving lenacapavir or switch from daily oral PrEP to the injectable drug.
Grinsztejn said 95% of participants opted to receive lenacapavir during the open-label extension.
During the first 12 months of the extension, researchers recorded just one new HIV infection among participants receiving lenacapavir. The infection occurred in a participant who had continued on lenacapavir from the earlier phase of the trial, while no HIV infections were reported among those who switched from oral PrEP.
Grinsztejn said that, from the start of the trial, there had been four HIV acquisitions in total among participants on lenacapavir. Three occurred during the earlier randomized phase and had already been reported, while one occurred during the open-label extension.
“The participant who acquired HIV during the open-label phase received all lenacapavir injections on time, and lenacapavir plasma level assessments are ongoing,” she said. Among participants who switched from daily oral PrEP to injectable lenacapavir, adherence reached 92% by week 52, she added.
Losso added that lenacapavir continued to demonstrate a strong safety profile, with no new safety signals identified during follow-up. “The tolerability and safety of lenacapavir in this open-label phase was very good. No new signals arose during this follow-up,” he said.
“Together, these studies confirm that twice-yearly lenacapavir for HIV prevention is safe and highly effective, and adherence to injections is high,” said Grinsztejn. She said there is “a growing consensus that lenacapavir for HIV prevention could fundamentally transform the global response to HIV.” Grinsztejn urged governments, donors, manufacturers and other partners to move quickly to expand access.
“If we deliver it where it is needed most, lenacapavir for HIV prevention has the potential to help curb the global pandemic,” said Grinsztejn.
Lenacapavir maintains high efficacy in PURPOSE 2
While the PURPOSE studies focused on preventing HIV infection, researchers also presented promising findings on a new long-acting treatment strategy for people already living with HIV. Researchers unveiled encouraging results from two Phase III trials evaluating what could become the world’s first once-weekly oral HIV treatment regimen for people whose virus is already suppressed.
Professor Kenneth Ngure said that while once-daily antiretroviral therapy has transformed HIV care, many people continue to face challenges with taking medication every day. “Many people with HIV want freedom of a long-acting option,” said Ngure. He said that current long-acting injectable treatments come with strict scheduling requirements.
He said the Phase III ISLEND-1 and ISLEND-2 trials evaluated a once-weekly oral single-tablet regimen combining islatravir and lenacapavir, which has the potential to become the first complete weekly oral treatment for virologically suppressed adults living with HIV.
The trials will continue for a further 48 weeks, with the complete 96-week results expected once follow-up is finished.
Dr Amy Colson of Community Resource Initiative and the Zinberg Clinic at Cambridge Health Alliance said the findings respond to a growing demand among people living with HIV for longer-acting oral treatment options that reduce the burden of daily medication.
“In survey studies, people with HIV on daily oral therapy have expressed a strong interest in longer-acting oral options,” Colson said.
In the ISLEND-1 trial, virologically suppressed adults taking the once-daily bictegravir-based regimen B/F/TAF were randomly assigned either to switch to the weekly pill or remain on their daily treatment. Ngure said the once-weekly regimen proved to be non-inferior to the daily regimen, with no cases of virological failure reported after 48 weeks.
“The study found that the weekly pill was non-inferior to B/F/TAF, with zero virologic failures at week 48, and was well tolerated,” said Ngure.
He said similar results were seen in the ISLEND-2 trial, which enrolled adults receiving a range of standard antiretroviral regimens. Participants who switched to the weekly tablet maintained viral suppression, and the regimen was again shown to be effective and well tolerated.
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Colson said both studies showed that switching to a once-weekly oral combination of islatravir and lenacapavir was as effective as remaining on standard daily antiretroviral therapy. The two studies enrolled more than 1,200 virologically suppressed adults across sites in Asia, Australia, Europe, the Americas, South Africa and other regions. Participants represented a diverse population, including women, older adults and people from different racial and ethnic backgrounds.
Colson said the once-weekly regimen was well tolerated in both studies, with a safety profile comparable to existing daily therapies.
She said that no clinically significant changes in CD4 cell counts, total lymphocyte counts or body weight were observed over the 48-week follow-up, while treatment discontinuations due to adverse events were rare. Adherence to the once-weekly tablets also remained high, suggesting that reducing dosing frequency did not lead to more missed doses. She noted that participants in the open-label ISLEND-2 trial also reported a strong preference for the weekly regimen, with 78% saying they were more or much more satisfied with the once-weekly treatment than with their previous daily medication.
“The ISLEND-1 and ISLEND-2 trials provide a robust demonstration of the efficacy and safety of the once-weekly fixed-dose combination of islatravir-lenacapavir,” said Colson. “Islatravir-lenacapavir has the potential to offer people living with HIV an oral, long-acting alternative to the current paradigm of daily dosing.”
Ahead of the conference, Gilead and Merck (known as MSD outside the United States and Canada) reported positive topline findings from the first 48 weeks of the ISLEND-1 and ISLEND-2 trials. The companies said they intend to submit the data to regulators worldwide, with detailed results being presented publicly for the first time at AIDS 2026.
“Treatment needs to fit into people’s lives, not the other way around,” said Ngure.
“People living with HIV need new treatment options that offer flexibility, and a weekly pill could broaden the choices available for adults with virological suppression,” said Ngure. “We are excited to share these results at AIDS 2026.”
