On November 6, 2026, Gilead Sciences announced one-year results from PURPOSE 5, an open-label Phase 2 trial in the UK and France. It is the first randomised study designed specifically to compare how well people stay on a long-acting HIV prevention option versus daily pills. The trial enrolled people who were not taking PrEP: 267 participants, of whom 72.3% were cisgender men, 7.1% cisgender women and 20.6% gender-diverse people. 37.8% had never used PrEP. Participants were randomised 2:1 to twice-yearly injectable lenacapavir (sold as Yeztugo in the US and Yeytuo in the UK) or daily oral F/TDF (Truvada and its generics). The data will be presented at HIV Glasgow 2026.

Why It Matters

**The biggest weakness in HIV prevention has been adherence, not efficacy, and this is the first randomised evidence that long-acting PrEP fixes it for people starting out.** Daily pills work when taken. The problem is that many people stop or take them only some of the time, especially younger users and those new to PrEP. A two-shot-a-year option that keeps nearly twice as many people protected at one year makes the case for payers to cover it, as Gilead's Yeztugo revenue keeps growing ([our coverage](/stories/gilead-q3-prep-yeztugo-305m)). It is also relevant to the newer PrEP distribution businesses, including Grindr's freshly closed **Freddie** acquisition ([our coverage](/stories/grindr-purposemed-freddie-250m)) and the telehealth platforms competing to be the sexual-health subscription layer. Access is still the limit. US clinics report that a large share of patients prescribed injectable PrEP never get the first shot because of prior-authorisation and pharmacy-benefit problems ([our coverage](/stories/injectable-prep-insurance-barriers-idweek)). A **$40-a-year generic** has been cleared for 120 low-income countries but not for the US market ([our coverage](/stories/dr-reddys-generic-lenacapavir-prep)). PURPOSE 5 shows the product keeps people on PrEP. Whether that turns into fewer infections depends on what insurers and health systems do next.

The headline. At week 52, 85.6% (154 of 180) of lenacapavir participants were still persistent, compared with 46.3% (37 of 80) on daily pills. The difference was 39.3 percentage points (p<0.0001). There were zero HIV acquisitions in the lenacapavir arm. The pill arm had one, and drug-level testing showed that person was taking fewer than two doses a week. Serious adverse events were similar (3.9% vs 3.4%), and investigators judged none related to treatment. Injection-site reactions were common but mostly mild or moderate: Gayety, reading the release, notes nodules in 67.8% and pain in 60% of lenacapavir recipients. No one stopped lenacapavir because of side effects.

The fine print. The two arms were measured differently. For the injection, persistence meant getting both shots on time (day 1 and week 26, ±2 weeks) and attending the week-52 visit. For pills, it meant dried-blood-spot drug levels consistent with at least four doses a week at weeks 13, 26, 39 and 52, which is a harder bar to clear. The trial is open-label and sponsored by Gilead, and the results come from a press release, not a peer-reviewed paper. Retention was high in both arms (89.4% vs 83.9% attended week 52).

Sources

Update — 2026-11-08

Initial entry — story first created.