Once‑Weekly Oral HIV Pill Maintains Viral Suppression Through 48 Weeks in Phase 3 Trial

A phase 3 trial published in The Lancet found that adults with HIV-1 who switched from daily oral antiretroviral therapy to a once-weekly single-tablet regimen of islatravir and lenacapavir maintained viral suppression through 48 weeks as effectively as those who stayed on standard daily treatment.

The finding is medically significant because, if regulators approve it, the combination could become the first once-weekly complete oral single-tablet regimen for HIV treatment. For patients, that would offer a new option between the daily pills that remain the standard of care and long-acting alternatives that are mostly injectable rather than weekly oral medicines.

The study, called ISLEND-2, was a multicenter, randomized phase 3 switch trial in adults with HIV-1 who were already virologically suppressed, meaning the virus was controlled to very low levels, on a stable oral regimen. Researchers tested a once-weekly tablet containing islatravir 2 milligrams plus lenacapavir 300 milligrams against continued daily standard-of-care treatment. At Week 48, the weekly regimen met the study’s main goal of showing non-inferiority, meaning it worked at least as well as staying on daily therapy for maintaining viral suppression.

By the FDA snapshot analysis, 0.3% of participants in the once-weekly islatravir-lenacapavir group had HIV-1 RNA of 50 copies per milliliter or higher at Week 48, compared with 1.3% of those who remained on daily standard-of-care regimens.

The trial summary described the weekly regimen as generally well tolerated, but adverse events linked to treatment were more common in the weekly-pill group than in the standard-care group. According to the sponsors, treatment-related adverse events occurred in 18% of participants taking islatravir-lenacapavir, versus less than 1% among those who stayed on standard care. The most common treatment-related side effects in the weekly group were headache, reported in 5% of participants, nausea in 3%, and diarrhea in 3%.

Even so, discontinuations due to adverse events were low: 1% in the weekly-pill group and less than 1% in the standard-care group, according to the sponsor summary. The sponsors also reported that CD4+ and lymphocyte counts remained stable through Week 48, an especially watched safety measure for this drug combination.

That point matters because islatravir has a notable safety history. In 2021, some islatravir programs were placed on partial clinical hold by the U.S. Food and Drug Administration after earlier studies found decreases in lymphocyte and CD4+ T-cell counts, which are key immune cells. Merck later adjusted dosing and development plans. The new report of stable counts through 48 weeks is therefore important, though it does not settle longer-term safety questions.

Patients who switched to the once-weekly pill also reported higher treatment satisfaction and lower treatment burden at Week 48, according to sponsor-reported patient-reported outcomes. Those measures can matter in HIV care, where treatment is long term and maintaining adherence is essential to keeping the virus suppressed.

Lenacapavir is already known in HIV treatment as the capsid inhibitor sold as Sunlenca, which was approved in 2022 for heavily treatment-experienced patients with multidrug-resistant HIV. But this weekly oral combination with islatravir is a different, investigational use. The ISLEND-2 results were also presented in a late-breaking session at AIDS 2026 in Rio de Janeiro.

For now, the regimen remains investigational and is not approved for this use. Gilead and Merck have said the phase 3 data will support regulatory submissions. What the new trial shows is that, over 48 weeks, a once-weekly oral switch regimen can maintain HIV suppression in adults already stable on treatment, while longer follow-up will be important to clarify durability and safety.