Long-Acting Oral HIV Regimen Shows Sustained Success
NEW data presented at the 2025 European AIDS Clinical Society (EACS) Congress suggest that a once-weekly oral regimen combining islatravir and lenacapavir could mark a major advance in HIV treatment convenience. Findings from a Phase 2 trial (NCT05052996) showed that people with HIV-1 who switched from daily antiretroviral therapy to this weekly two-drug regimen maintained full viral suppression through 96 weeks, with no cases of virologic failure or drug resistance.
The study enrolled adults who were already virologically suppressed on a standard daily combination of bictegravir, emtricitabine, and tenofovir alafenamide. Participants were randomised to continue daily therapy or to switch to once-weekly islatravir 2 mg plus lenacapavir 300 mg. Of the 52 participants who began the once-weekly regimen, 47 continued into the 48-week extension phase, completing nearly 2 years of follow-up.
At 96 weeks, all participants on the islatravir-lenacapavir combination maintained undetectable viral loads, and mean adherence-assessed by pill count was 99.3%. No emergent resistance to either agent was observed, and safety data remained favourable throughout the study period.
Safety and Tolerability Comparable to Standard Therapy
Treatment with the once-weekly regimen was well tolerated. Just under one in five participants (19.2%) experienced mild or moderate drug-related side effects, and no severe adverse events related to treatment were reported. Two participants discontinued the study, though neither due to drug-related effects.
CD4+ T-cell counts showed minimal changes, with a mean decrease of 33 cells/μL (95% CI: −86 to 20), while median weight and BMI remained stable over 2 years. The consistent efficacy, safety, and adherence profile suggest that weekly oral dosing could provide a simpler alternative for people living with HIV who wish to avoid daily tablets or injectable regimens.
Phase 3 Trials Now Underway
The promising Phase 2 results underpin ongoing global Phase 3 trials (ISLEND-1 and ISLEND-2) which aim to confirm the efficacy and safety of once-weekly oral islatravir plus lenacapavir as a complete regimen for HIV-1. If successful, this would represent the first fully oral, once-weekly treatment option for people living with HIV.
Researchers at EACS 2025 emphasised that such simplified dosing could improve quality of life and adherence, supporting long-term viral suppression and reducing treatment fatigue among patients.
Reference
Colson AE et al. Oral weekly islatravir plus lenacapavir in virologically suppressed people With HIV-1: 96 week outcomes from a phase 2 study. PS15.5.LB. EACS 2025, 15-18 October, 2025.
