Gilead and Merck’s investigational once‑weekly HIV pill combining islatravir and lenacapavir met Phase 3 ISLEND trial endpoints, maintaining viral suppression with a safety profile comparable to daily therapy. If approved, ISL/LEN could become the first long‑acting oral HIV treatment taken once weekly.
Written By: Shaik Yasmeen, PharmD
Reviewed By: Pharmacally Editorial Team
Gilead Sciences and Merck reported positive Phase 3 results from the ISLEND-1 and ISLEND-2 studies evaluating an investigational once-weekly oral HIV regimen combining islatravir (2 mg) and lenacapavir (300 mg). At Week 48, the single-tablet regimen maintained viral suppression at rates statistically non-inferior to daily antiretroviral therapies, with a safety profile comparable to standard regimens. If approved, ISL/LEN would become the first long-acting oral HIV treatment taken once weekly.
Complementary Long-Acting Mechanisms
The regimen combines Merck’s islatravir, a next-generation nucleoside analog, with Gilead’s lenacapavir, a first-in-class capsid inhibitor. Islatravir blocks reverse transcriptase through multiple mechanisms, including translocation inhibition and chain termination, while lenacapavir disrupts capsid function across several stages of the viral lifecycle.
The complementary mechanisms and prolonged pharmacokinetic profiles of both agents enable once-weekly oral dosing, offering a potential alternative to lifelong daily HIV treatment.
ISLEND-1 and ISLEND-2 Outcomes
ISLEND-1 (NCT06630286) enrolled adults with virologically suppressed HIV who had been receiving BIKTARVY for at least six months. In the randomized, double-blind study, participants either switched to once-weekly ISL/LEN or continued daily BIKTARVY. The regimen demonstrated statistical non-inferiority based on the proportion of participants with HIV-1 RNA levels of at least 50 copies/mL at Week 48 under the FDA Snapshot analysis.
ISLEND-2 (NCT06630299) evaluated a broader population of virologically suppressed adults receiving stable standard-of-care antiretroviral regimens. In the open-label study, participants either switched to ISL/LEN or remained on their existing therapy. The once-weekly regimen again achieved non-inferior viral suppression compared with daily treatment.
Across both trials, investigators reported a safety profile generally comparable to the respective comparator regimens, with no new treatment-emergent safety signals identified.
Expanding Long-Acting HIV Options
The results support growing interest in long-acting HIV therapies that reduce treatment burden while maintaining durable viral suppression. Gilead’s Jared Baeten highlighted the flexibility and discretion that less frequent dosing could provide for people living with HIV, while Merck’s Eliav Barr emphasized the potential to expand treatment choices through a novel weekly oral regimen.
The companies plan to submit the Phase 3 data to regulatory authorities globally and present detailed findings at a future scientific meeting.
Broader Pipeline Development
Beyond the ISL/LEN program, Gilead continues to advance lenacapavir across its HIV treatment and prevention portfolio, while Merck is evaluating islatravir in additional daily and once-weekly combination regimens.
If regulators approve the regimen, ISL/LEN could become the first once-weekly oral HIV treatment, adding a new option between traditional daily pills and long-acting injectable therapies. Detailed Phase 3 data expected at future scientific meetings will help define the regimen’s role in long-term HIV management.
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About the Writer
Shaik Yasmeen (LinkedIn) is a Pharm.D graduate with interests in clinical pharmacy, pharmacovigilance, and medical writing. She has gained experience through hospital clinical postings, patient case reviews, case presentations, and literature evaluation. Passionate about evidence-based healthcare, she is committed to creating accurate and engaging medical content while continuously expanding her professional knowledge.