A phase 2 randomized study evaluating the efficacy and safety of once-weekly oral islatravir plus lenacapavir (ISL+LEN) in virologically suppressed adults with HIV found that ISL+LEN maintained high rates of virologic suppression through 48 weeks, with no treatment-related grade 3 or greater adverse events or serious adverse events. These findings suggest that ISL+LEN may offer a promising long-acting oral regimen to address adherence challenges in HIV treatment. The study is published in Annals of Internal Medicine.
Researchers funded by Gilead Sciences evaluated the use of once-weekly ISL+LEN compared with daily oral bictegravir, emtricitabine, and tenofovir alafenamide combination (B/F/TAF) in persons with HIV-1 infection. Outcomes of interest included rates of virologic suppression through week 48 and adverse events.
The open-label, active-controlled trial included 104 participants across 44 U.S. sites who had HIV-1 RNA viral load of less than 50 copies/mL while receiving daily B/F/TAF for at least 24 weeks.
The participants were randomly assigned to receive either once-weekly ISL (2 mg) plus LEN (300 mg) or continue daily B/F/TAF for 48 weeks. The researchers found that at week 24, one ISL+LEN participant and none in the B/F/TAF group had HIV-1 RNA viral load of 50 copies/mL or more and almost all of the participants in both groups maintained HIV-1 RNA viral load of less than 50 copies/mL. At week 48, viral suppression rates were 94.2% for ISL+LEN and 92.3% for B/F/TAF, with no virologic rebound or emergent resistance detected. Treatment-related adverse events were mild in both groups.
There were no discontinuations due to treatment-related adverse events, and changes in CD4+ T-cell and lymphocyte counts were not clinically meaningful. Adherence was high in both groups, with a greater proportion achieving at least 95% adherence in the ISL+LEN group. These results support further evaluation of ISL+LEN in phase 3 trials to assess safety and efficacy in a larger, global study population.
Reference:
Amy E. Colson, Gordon E. Crofoot, Peter J. Ruane, et al. Once-Weekly Oral Islatravir Plus Lenacapavir Versus Daily Oral Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Persons With HIV-1: A Phase 2 Randomized Study. Ann Intern Med. [Epub 23 December 2025]. doi:10.7326/ANNALS-25-01939