This article was updated 10/17/2025 at 3:55pm to fix an error in the data.

By Meaghan Lee Callaghan

An investigational once-weekly oral combination therapy containing islatravir (ISL; Merck) and lenacapavir (LEN; Gilead) was found safe and effective in virologically suppressed people living with HIV in a phase 2 study.

The researchers also found high adherence to the regimen.

“Switching to an investigational once-weekly combination regimen of islatravir and lenacapavir enabled people with HIV to maintain viral suppression for two years and are consistent with the previously presented week 24 and week 48 results,” Brian Plummer, a spokesperson for Gilead, told Infectious Disease Special Edition.

Safe and Effective

The data, presented at EACS 2025, in Paris, were based on a phase 2 trial (ClinicalTrials.gov Identifier: NCT05052996) with reporting out to 96 weeks (abstract PS15.5.LB).

In the study, participants (N=104) were randomized 1:1 to receive bictegravir-emtricitabine-tenofovir alafenamide or ISL/LEN. Following the 48-week randomized phase was a 48-week extension phase, where 47 of the 52 participants who received ISL/LEN reported data. In that arm, the median age of participants was 40 years, and 19.2% identified as female.

The investigators found that all participants in the ISL/LEN arm had HIV RNA levels less than 50 copies/mL at 96 weeks or discontinuation of the drug, and they saw no emergent resistance to ISL or LEN. In addition, only 10 participants (19.2%) had a drug-related adverse event (AE), and no grade 3 or higher drug-related AEs were reported. However, two participants (3.8%) chose to discontinue due to AEs unrelated to the study drug.

The researchers also observed a slight decrease in CD4+ T-cell count (–33 cells/mcL; 95% CI,–86 to 20 cells/mcL) and lymphocyte count (–0.2X103/mcL; 95% CI, –0.3 to –0.1X103/mcL). Weight change was also minimal (+0.1 kg; 95% CI, –2.6 to 1.8 kg), as well as body mass index (+0.04 kg/m2; 95% CI, –0.9 to 0.6 kg/m2).
Of note, the investigators saw near perfect adherence to the study drugs, at 99.3%.

Collaboration for the Future

The data also mark positive results from a drug combination therapy from different drugmakers: Gilead and Merck. “We are pleased to collaborate with Merck because of the complementary profiles of combining ISL and LEN that could lead to potentially the first weekly oral HIV treatment option,” Mr. Plummer told IDSE. Two phase 3 studies already are underway. Studies ISLEND-1 (NCT06630286) and ISLEND-2 (NCT06630299) have finished enrolling and just begun, with an estimated primary completion in April 2026.

Mr. Plummer is an employee of Gilead. Many study authors reported financial relationships with Gilead and Merck, among other companies.