Gilead Lenacapavir PURPOSE 5 results show that twice-yearly injectable lenacapavir delivered significantly higher one-year persistence than daily oral emtricitabine/tenofovir disoproxil fumarate (F/TDF) for HIV pre-exposure prophylaxis (PrEP). Gilead Sciences, Inc. (Nasdaq: GILD) announced the results on November 6, 2026. The trial enrolled people in the United Kingdom and France who would benefit from PrEP, and the data will be presented at HIV Glasgow 2026.
The Gilead Lenacapavir PURPOSE 5 headline numbers are clear. At Week 52, 85.6% (154/180) of participants receiving twice-yearly lenacapavir remained persistent on PrEP, compared with 46.3% (37/80) of those taking once-daily F/TDF. The difference of 39.3 (95% CI: 26.66% to 51.41%) was statistically significant (p<0.0001). Gilead also reported zero HIV acquisitions among lenacapavir recipients during the 52-week study period. The company describes PURPOSE 5 as the first randomized study designed specifically to compare persistence between a long-acting HIV prevention option and daily oral PrEP in people not currently taking PrEP.
The results arrive against a sobering global backdrop. Approximately 1.2 million people acquired HIV worldwide in 2025, according to UNAIDS, which underscores the need for prevention options people can sustain over time. Gilead notes that persistence remains one of the most important determinants of real-world PrEP effectiveness. Daily oral F/TDF is currently the most commonly used oral PrEP medication globally. Starting PrEP, in other words, is only the first step.
Why the Gilead Lenacapavir PURPOSE 5 Persistence Gap Matters for HIV Prevention
Professor Chloe Orkin, MBE, Clinical Professor of Infection and Inequities at Queen Mary University of London, framed the findings in practical terms. She stressed that “persisting on PrEP is critical to preventing HIV acquisition.” She said people in France and the United Kingdom who received twice-yearly injections were much more likely to keep taking PrEP effectively than those on daily tablets. She also noted that the study reached a high proportion of new PrEP users, which strengthens the relevance of the Gilead Lenacapavir PURPOSE 5 findings for people just starting prevention.
Jared Baeten, MD, PhD, is Senior Vice President of Clinical Development and Virology Therapeutic Area Head at Gilead Sciences. He said the study was built to examine one of the biggest challenges in HIV prevention today: helping people stay on PrEP for as long as they need protection. In his view, the data show that twice-yearly lenacapavir has the potential to close the gap between starting and staying on PrEP. He tied this to efforts to end the HIV epidemic in Europe and around the world.
Gilead’s announcement says that awareness and availability of PrEP have grown, but persistence remains a challenge across many settings. Daily oral PrEP is highly effective when taken as prescribed, yet real-world studies have consistently shown that many people stop within the first year. The Gilead Lenacapavir PURPOSE 5 study was designed to test that exact problem. By reducing dosing to one injection every six months, twice-yearly lenacapavir may offer a discreet and convenient option for some people more vulnerable to HIV acquisition. Gilead cites up to a full year of protection after the second dose.
Gilead Lenacapavir PURPOSE 5 Trial Design, Participants and Persistence Definitions
The Gilead Lenacapavir PURPOSE 5 study is an ongoing Phase 2, randomized, open-label trial. It evaluates PrEP persistence among people with HIV prevention needs in the United Kingdom and France who were not taking PrEP at enrollment. Participants were randomized 2:1 to twice-yearly lenacapavir or daily oral F/TDF and were followed for 52 weeks. PURPOSE 5 sits within Gilead’s broader PURPOSE clinical development program.
PURPOSE 5 Trial Design
| Parameter | Detail |
|---|---|
| Sponsor | Gilead Sciences, Inc. (Nasdaq: GILD) |
| Phase | Phase 2, ongoing |
| Design | Randomized, open-label |
| Randomization ratio | 2:1 (lenacapavir : F/TDF) |
| Locations | United Kingdom and France |
| Population | People with HIV prevention needs not taking PrEP at enrollment |
| Follow-up | 52 weeks |
| Total enrolled | 267 |
| Presentation venue | HIV Glasgow 2026 (date and session: Not disclosed) |
| ClinicalTrials.gov identifier | Not disclosed in the release |
A total of 267 participants enrolled: cisgender men (72.3%), cisgender women (7.1%) and gender-diverse individuals (20.6%). Of these, 37.8% were PrEP-naïve at baseline. Retention was high in both arms, with 89.4% of the lenacapavir group and 83.9% of the F/TDF group attending the Week 52 visit. One HIV acquisition was reported in the F/TDF group. Drug-level analysis at diagnosis was consistent with fewer than two F/TDF doses per week.
Gilead applied strict protocol definitions of persistence. For lenacapavir, persistence meant an on-time injection at Day 1/baseline and Week 26 (plus or minus two weeks), plus an on-time follow-up visit at Week 52. For F/TDF, it meant dried blood spot tenofovir diphosphate (TFV-DP) concentrations consistent with at least four doses per week (≥700 fmol/punch) at Weeks 13, 26, 39 and 52. Because the two arms were measured differently, readers should interpret the comparison with that design in mind.
Week 52 Results
| Endpoint | Lenacapavir (twice-yearly) | Daily oral F/TDF |
|---|---|---|
| Persistent on PrEP at Week 52 | 85.6% (154/180) | 46.3% (37/80) |
| Difference | 39.3 (95% CI: 26.66% to 51.41%) | p<0.0001 |
| HIV acquisitions | 0 | 1 (drug levels consistent with fewer than 2 doses/week) |
| Attended Week 52 visit | 89.4% | 83.9% |
| Approximate ratio of persistence (editorial calculation) | about 1.85x | reference |
Gilead Lenacapavir PURPOSE 5 Safety Profile: Injection-Site Reactions and Yeztugo Warnings
The safety profile in the Gilead Lenacapavir PURPOSE 5 trial was generally consistent with earlier lenacapavir PrEP studies. Serious adverse events were uncommon. They occurred in 3.9% of lenacapavir participants and 3.4% of F/TDF participants, and investigators judged none related to study treatment. No participant discontinued lenacapavir because of adverse events.
The most common treatment-related events were mild or moderate injection-site reactions linked to subcutaneous administration. These included nodules (67.8%), pain (60.0%), induration (20.6%) and erythema (17.8%). Gilead’s U.S. Important Safety Information lists injection site reactions, headache and nausea as the most common adverse reactions (5% or more) across Yeztugo clinical trials.
PURPOSE 5 Safety Data
| Safety measure | Lenacapavir | F/TDF |
|---|---|---|
| Serious adverse events | 3.9% | 3.4% |
| Serious events related to study treatment | None (per investigators) | None (per investigators) |
| Discontinuations due to adverse events | None | Not disclosed |
| Injection-site nodules | 67.8% | Not applicable |
| Injection-site pain | 60.0% | Not applicable |
| Induration | 20.6% | Not applicable |
| Erythema | 17.8% | Not applicable |
Prescribers and patients should also note Yeztugo’s boxed warning. Drug-resistant HIV-1 variants have been identified in people with undiagnosed HIV-1 infection. HIV-1 testing is therefore required before initiation and before each injection, and Yeztugo is contraindicated in people with unknown or positive HIV-1 status. Residual drug concentrations may remain in circulation for 12 months or longer after the last injection. For people at continuing risk, Gilead advises considering alternative PrEP, initiated within 28 weeks of the last injection. Yeztugo must be given subcutaneously, because intradermal injection has been linked to serious reactions including necrosis and ulcer.
Yeztugo (lenacapavir) Dosing, per U.S. Important Safety Information
| Phase | Regimen |
|---|---|
| Initiation, Day 1 | 927 mg subcutaneous (2 x 1.5 mL injections) plus 600 mg oral (2 x 300 mg tablets) |
| Initiation, Day 2 | 600 mg oral |
| Continuation | 927 mg subcutaneous every 6 months (26 weeks) from last injection, plus or minus 2 weeks |
| Anticipated delay over 2 weeks | 300 mg oral once every 7 days, for up to 6 months, until injections resume |
| Missed injection (over 28 weeks, no tablets taken) | Restart initiation dosing if clinically appropriate |
| Eligibility | Adults and adolescents weighing at least 35 kg who are at risk for HIV-1 acquisition |
