Gilead & Merck: Once-weekly islatravir/lenacapavir (ISL/LEN) maintained viral suppression in Phase 3 ISLEND trials

Trials and design

Two multicenter Phase 3 trials (ISLEND-1 and ISLEND-2) evaluated a once-weekly single-tablet regimen of islatravir 2 mg/lenacapavir 300 mg (ISL/LEN) in adults with virologic suppression on stable antiretroviral therapy for ≥6 months. ISLEND-1 was randomized, double-blind and active-controlled versus BIKTARVY; ISLEND-2 was randomized, open-label and active-controlled versus participants’ standard-of-care daily regimens. Participants received initial doses on Day 1 and Day 2 followed by once-weekly dosing from Day 8 to Week 96. The primary endpoint was the proportion with HIV-1 RNA ≥50 copies/mL at Week 48 by the FDA-defined Snapshot algorithm.

Key efficacy results at Week 48

Both trials met the primary endpoint for noninferiority. In ISLEND-1, 0% of participants who switched to ISL/LEN had HIV-1 RNA ≥50 copies/mL at Week 48 versus 0.3% on BIKTARVY. In ISLEND-2, 0.3% on ISL/LEN versus 1.3% on standard-of-care had HIV-1 RNA ≥50 copies/mL. These outcomes will be presented at AIDS 2026 and are intended to support regulatory submissions.

Safety, tolerability and patient-reported outcomes

Safety profiles were generally similar to comparators. ISLEND-1 reported treatment-related AEs in 13.5% (ISL/LEN) versus 13.2% (BIKTARVY); common AEs included nausea and headache (~3%). Serious AEs and discontinuations were low in both arms. ISLEND-2 reported treatment-related AEs of 18% with ISL/LEN versus <1% with standard of care; common ISL/LEN AEs included headache (5%), nausea (3%) and diarrhea (3%). CD4+ T-cell and lymphocyte counts and body weight remained stable through Week 48, and no discontinuations were attributed to CD4/lymphocyte declines. Participants switching to ISL/LEN reported higher treatment satisfaction and lower treatment burden. ISL/LEN is investigational and not approved for use.