First weekly oral HIV regimen maintains viral suppression in phase 3 trial

Clinical takeaway: For adults with sustained viral suppression, a once-weekly oral regimen may become an alternative to daily antiretroviral therapy if approved. A less frequent oral option could improve adherence for some patients while avoiding injections required with current long-acting therapies.

Daily single-tablet regimens have transformed HIV care, but taking medication every day remains challenging for some patients. Long-acting injectable regimens have expanded treatment options, but not all patients want or can receive injections. A phase 3 trial found that a once-weekly oral combination maintained viral suppression as effectively as a standard daily regimen in adults with well-controlled HIV.

The ISLEND-1 trial enrolled 607 adults with HIV-1 who had maintained viral suppression for at least 6 months on once-daily bictegravir/emtricitabine/tenofovir alafenamide. Participants were randomized either to switch to once-weekly oral islatravir plus lenacapavir or to continue their daily regimen.

At 48 weeks, no participants receiving the weekly regimen had HIV RNA levels of 50 copies/mL or higher, compared with one participant (0.3%) who continued daily therapy. Viral suppression below 50 copies/mL was maintained in 93.4% of patients receiving weekly treatment and 92.4% receiving daily therapy, meeting the trial's prespecified criteria for noninferiority.

Safety was similar between groups. Treatment discontinuation because of adverse events occurred in 2.0% of participants receiving weekly therapy and 1.7% receiving daily therapy, while serious adverse events occurred in 5.3% and 4.6%, respectively. CD4+ T-cell counts remained stable in both groups.

If approved, a once-weekly oral regimen could fill an important gap between daily pills and long-acting injectable therapy. For patients who struggle with daily adherence but prefer to avoid injections, it may provide another option for maintaining long-term viral suppression.

Source: Rockstroh JK, et al. (2026 Jul 29) N Engl J Med. Phase 3 Trial of Weekly Oral Islatravir–Lenacapavir for HIV-1 Treatment