Gilead Sciences and Merck (known as MSD outside the United States and Canada) have announced positive detailed results from the Phase 3 ISLEND-1 and ISLEND-2 clinical trials evaluating the investigational once-weekly oral HIV treatment regimen combining islatravir (2 mg) and lenacapavir (300 mg) (ISL/LEN). The findings, presented at the 26th International AIDS Conference (AIDS 2026), demonstrated that the once-weekly single-tablet regimen effectively maintained virologic suppression in adults living with HIV who switched from standard daily antiretroviral therapies.

The 48-week data showed that ISL/LEN was non-inferior to current guideline-recommended daily HIV treatment regimens, while maintaining a safety profile comparable to existing therapies and identifying no new safety concerns. The results are expected to form the basis for regulatory submissions.

The ISLEND-1 and ISLEND-2 studies evaluated the efficacy and safety of switching virologically suppressed adults from daily oral HIV therapies to the once-weekly investigational regimen. If approved, ISL/LEN could become the first once-weekly oral treatment option for adults living with HIV.

In the ISLEND-1 trial, participants switching from Biktarvy maintained virologic suppression through Week 48, with no participants receiving ISL/LEN recording HIV-1 RNA levels of 50 copies/mL or higher, compared with 0.3 percent of participants who continued on Biktarvy. The incidence of treatment-related adverse events, serious adverse events, treatment discontinuations and changes in CD4+ T-cell counts remained comparable between both treatment groups.

The ISLEND-2 trial similarly met its primary endpoint, with only 0.3 percent of participants receiving ISL/LEN experiencing virologic failure compared with 1.3 percent among those continuing standard daily antiretroviral therapy. Participants receiving the once-weekly regimen also reported higher treatment satisfaction and lower treatment burden than those taking daily HIV medications.

The investigational therapy combines Merck's islatravir, a next-generation nucleoside analogue with multiple mechanisms of action, and Gilead's lenacapavir, a first-in-class capsid inhibitor designed to disrupt HIV replication at multiple stages of its lifecycle. Their complementary pharmacokinetic profiles enable convenient once-weekly oral dosing.

Commenting on the findings, Jürgen Rockstroh, Department of Medicine, University Hospital Bonn, Germany, said the results demonstrate the potential of ISL/LEN to become the first once-weekly oral single-tablet HIV treatment, offering an important alternative to existing daily therapies.

Amy Colson, Research Director at Community Resource Initiative and Medical Director of the Zinberg Clinic at Cambridge Health Alliance, noted that a once-weekly treatment option could provide greater flexibility and choice for people living with HIV while supporting long-term treatment adherence.

The investigational combination of islatravir and lenacapavir has not yet been approved for use. Gilead and Merck stated that the Phase 3 findings will support upcoming regulatory filings as they seek approval for what could become a new treatment option for adults living with virologically suppressed HIV.