FOSTER CITY, Calif. & RAHWAY, N.J., July 22, 2026
Gilead Sciences and Merck announced detailed results from the Phase 3 ISLEND-1 and ISLEND-2 clinical trials demonstrating that the investigational once-weekly oral combination of islatravir and lenacapavir (ISL/LEN) successfully maintained virologic suppression in adults with HIV who switched from daily antiretroviral therapy. The studies met their primary endpoints at Week 48, showing that the once-weekly regimen was non-inferior to standard daily HIV treatments while maintaining a safety profile comparable to existing therapies. The findings, presented at the 26th International AIDS Conference (AIDS 2026), support regulatory submissions and position ISL/LEN as the potential first once-weekly oral HIV treatment for virologically suppressed adults.
Phase 3 ISLEND Trials Meet Primary Endpoints
The ISLEND-1 randomized, double-blind Phase 3 trial evaluated patients who switched from Biktarvy® to once-weekly ISL/LEN. At Week 48, no participants receiving ISL/LEN experienced HIV-1 RNA levels of at least 50 copies/mL, compared with only one participant remaining on Biktarvy, demonstrating non-inferior efficacy in maintaining viral suppression. The companion ISLEND-2 open-label Phase 3 study enrolled adults receiving a variety of standard oral antiretroviral regimens and likewise achieved its primary endpoint. Only 0.3% of participants receiving ISL/LEN experienced virologic failure versus 1.3% among those continuing standard daily therapy. Together, the results confirm that weekly oral dosing can provide durable viral control comparable to established daily HIV treatments.
Safety Profile and Patient Satisfaction Support Weekly Therapy
Across both Phase 3 studies, the investigational regimen demonstrated a safety profile generally consistent with comparator treatments, with no new safety concerns identified. The most frequently reported treatment-related adverse events included headache, nausea, and diarrhea, while discontinuation rates due to adverse events remained low. CD4+ T-cell counts and lymphocyte levels remained stable throughout the 48-week evaluation period, and no clinically meaningful differences in body weight were observed between treatment groups. In ISLEND-2, patient-reported outcomes showed higher treatment satisfaction and reduced treatment burden among participants receiving once-weekly ISL/LEN compared with those continuing daily oral therapy, highlighting the potential quality-of-life advantages of less frequent dosing.
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Potential First Once-Weekly Oral HIV Treatment
The investigational regimen combines Merck’s islatravir, a next-generation nucleoside analog that inhibits HIV replication through multiple mechanisms, with Gilead’s lenacapavir, a first-in-class capsid inhibitor that disrupts HIV at several stages of its lifecycle. Both agents possess pharmacokinetic properties that enable once-weekly administration as a complete single-tablet regimen. Gilead and Merck stated that the Phase 3 findings will support global regulatory submissions while reinforcing their long-term strategy to expand long-acting HIV treatment options. If approved, ISL/LEN could become the first once-weekly oral treatment for adults living with HIV, offering a new alternative to daily antiretroviral therapy.
Source: Gilead Sciences press release
