Weekly oral HIV treatment shows efficacy and safety

Researchers report that once-weekly treatment with islatravir plus lenacapavir (ISL+LEN) in virologically suppressed adults with HIV has safely maintained high rates of virologic suppression through 48 weeks.

The study was published on Dec. 22, 2025 in Annals of Internal Medicine.

The investigators compared once-weekly ISL+LEN  to a daily oral bictegravir, emtricitabine, and tenofovir alafenamide combination (B/F/TAF) in subjects with HIV-1 infection.

Outcomes included rates of virologic suppression through week 48 and adverse events.

Investigators in the phase 2, open-label trial enrolled 104 subjects (USA) who had achieved an HIV-1 RNA viral load of less than 50 copies/mL while receiving daily B/F/TAF for at least 24 weeks.

The researchers randomized the subjects (102 in each cohort) to receive either once-weekly ISL (2 mg) plus LEN (300 mg) or daily B/F/TAF. The trial lasted for 48 weeks.

They reported that, at week 24, one ISL+LEN subject and no B/F/TAF subjects had an HIV-1 RNA viral load of 50 copies/mL or more, a difference of 1.9%.

At week 48, 94.2% and 92.3% of ISL+LEN and B/F/TAF subjects, respectively, achieved an HIV-1 RNA viral load of less than 50 copies/mL, a difference of 1.9%. There were no subjects in either group with an HIV-1 RNA viral load of 50 copies/mL or more.

Two ISL+LEN subjects discontinued treatment (before week 24) due to adverse events that were not related to the drug they used in the study.

The authors concluded, “Once-weekly oral ISL-plus-LEN maintained high rates of virologic suppression through week 48 and was not associated with any treatment-related grade 3 or greater or serious AEs… Once-weekly oral islatravir plus lenacapavir (ISL+LEN) has the potential to address adherence challenges with daily HIV-1 treatment.”