Lenacapavir PrEP: 86% Stuck With the Twice-Yearly Shot, 46% With Daily Pills
Gilead says 85.6% of people who started twice-yearly lenacapavir PrEP in a U.K. and France trial stayed persistent for a year, vs. 46.3% on daily pills.
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Twice-yearly lenacapavir PrEP kept 85.6% of people starting it persistent for a year in a U.K. and France trial, compared with 46.3% on daily F/TDF pills, Gilead Sciences said Friday, Nov. 6. “While starting on PrEP is important, persisting on PrEP is critical to preventing HIV acquisition,” said Chloe Orkin, a professor at Queen Mary University of London who’s scheduled to present the PURPOSE 5 results at HIV Glasgow on Monday.
No one on the shot got HIV, and one person on pills did. “In PURPOSE 5, people in France and the United Kingdom receiving twice-yearly lenacapavir injections were much more likely to keep taking PrEP effectively compared with those receiving daily PrEP tablets,” Orkin said in Gilead’s release.
Gilead’s ongoing Phase 2 trial randomly assigned two people to lenacapavir for every one on F/TDF, the daily pill sold as Truvada. “A total of 267 participants enrolled in the study, including cisgender men (72.3%), cisgender women (7.1%) and gender-diverse individuals (20.6%),” the release said.
None were taking PrEP when they joined, and 37.8% had never used it. “It is notable that the study was able to reach a high proportion of new PrEP users,” Orkin said. How PURPOSE 5 Measured Lenacapavir PrEP Persistence
The two groups weren’t held to the same yardstick. On the shot, persistence meant “receipt of on-time LEN injection at Day 1/baseline and week 26,” within two weeks either way, plus an on-time checkup at week 52, the release said.
People on pills counted only if dried blood spot tests at weeks 13, 26, 39 and 52 showed drug levels consistent with at least four doses a week. By those measures, 154 of 180 people on lenacapavir and 37 of 80 on F/TDF were persistent, and Gilead said the shot achieved “significantly higher one-year PrEP persistence.”
Those counts cover 260 of the 267 people who enrolled. “Participant retention across both groups remained high throughout the study, with 89.4% of participants in the lenacapavir group and 83.9% of participants in the F/TDF group attending the Week 52 study visit,” the release said.
The one HIV acquisition came in the pill group, where the person’s “drug-level analysis at the time of diagnosis was consistent with fewer than two doses of F/TDF per week,” according to Gilead. Nodules, Pain and Other Limits of Gilead’s Trial Data
Serious adverse events hit 3.9% of people on lenacapavir and 3.4% of people on pills. “Investigators determined that no serious adverse events were related to study treatment,” the release said.
The most common treatment-related problems were mild or moderate reactions where the shot went in, including nodules in 67.8% of people on lenacapavir and pain in 60%. “No participants discontinued treatment due to adverse events with lenacapavir,” Gilead said.
Everyone knew which PrEP they got, since the trial is open-label, and Gilead sponsors it. When the company announced PURPOSE 5 in October 2023, it said it would recruit “groups across France and the United Kingdom that are disproportionally affected by HIV and often underrepresented in clinical trials.”
The trial’s registry entry lists “cisgender men who have sex with men” among eligible groups, along with trans women, trans men, cisgender women and nonbinary people. It lists eight sites in the U.K. and six in France. In France, “136 people were enrolled in these centers,” said Dr. Jean-Michel Molina of Paris’ Saint-Louis Hospital, who coordinates the study there, in a September article by the HIV charity Sidaction (Gayety’s translation).
Gilead’s numbers come from its release, which doesn’t cite a published paper. “These data will be presented at HIV Glasgow 2026,” it said. NICE Draft Rejects Yeytuo for England’s NHS as France Waits
The U.K.’s medicines regulator, the MHRA, approved lenacapavir as Yeytuo on Dec. 19, 2025. The approval “marks the introduction of a 6-monthly long-acting preventative option,” Julian Beach, the agency’s interim executive director of healthcare quality and access, said then.
In September, though, draft guidance from the National Institute for Health and Care Excellence said lenacapavir shouldn’t be used on the NHS in England. The draft said “the cost-effectiveness estimates are above the range that NICE considers an acceptable use of NHS resources,” The Pharmaceutical Journal reported.
“Gilead needs to move on price,” Richard Angell, chief executive of the HIV charity Terrence Higgins Trust, said, according to the journal. NICE’s committee was due to meet again Nov. 3, and its project page still showed the appraisal “In progress” on Saturday.
In France, lenacapavir PrEP was available only inside a clinical trial as of Sidaction’s September report. “We have to wait for the HAS to rule on the conditions of its reimbursement,” said Solenn Bazin, an advocacy officer at the HIV group AIDES, in Gayety’s translation. She expected the HAS, France’s national health authority, to weigh in “in autumn 2026,” and price talks come after that. Yeztugo Lists at $28,218 a Year in the U.S.
The FDA approved lenacapavir for PrEP as Yeztugo on June 18, 2025, after PURPOSE 1 recorded zero infections among 2,134 cisgender women on the shot in sub-Saharan Africa. In PURPOSE 2, with two infections among 2,179 cisgender men and gender-diverse people, “99.9% of participants in the Yeztugo group did not acquire HIV infection,” Gilead said.
Yeztugo’s U.S. list price is $28,218 a year before insurance, The Associated Press reported on Nov. 2, and the shot brought in $305 million in the third quarter, Gayety reported. People don’t always take a daily pill, “and if you do not take it, you cannot get protected against HIV,” Carmen Pérez Casas, Unitaid’s HIV lead, said, according to the AP.
A generic from India’s Dr. Reddy’s Laboratories has won FDA tentative approval, a step that doesn’t allow U.S. sales, the company and its partners announced Nov. 2, and it will cost $40 a year in 120 low- and middle-income countries. “Even before generic availability, over 125,000 people in 10 early adopter African countries have already started Gilead’s lenacapavir,” Unitaid said.
Orkin, who co-chairs the Nov. 8 to 11 congress, is set to present abstract O21, “Higher persistence on twice-yearly lenacapavir versus daily F/TDF for PrEP in the UK and France in the PURPOSE 5 study,” at 10:50 a.m. GMT on Monday, Nov. 9 (2:50 a.m. PT), according to the congress’s published schedule.
