Gilead and Merck's Once-Weekly HIV Pill Matches Daily Therapy in Two Phase 3 Trials

An investigational once-weekly tablet combining Merck's islatravir and Gilead's lenacapavir kept HIV suppressed through 48 weeks in adults who switched from daily treatment, meeting the primary endpoint of two Phase 3 trials, the companies announced on July 21. The detailed company-reported results were featured in the press program of the 26th International AIDS Conference (AIDS 2026) and are due to be presented in late-breaking sessions on July 29.

The regimen, islatravir 2 mg/lenacapavir 300 mg (ISL/LEN), was noninferior to Gilead's daily Biktarvy in the ISLEND-1 trial and to other daily standard-of-care regimens in ISLEND-2, measured as the share of participants with HIV-1 RNA of 50 copies/mL or more at Week 48 under the FDA-defined snapshot algorithm.

The results

In the double-blind ISLEND-1 trial, no participants who switched to ISL/LEN had a viral load at or above that threshold at Week 48, compared with one participant (0.3%) who stayed on Biktarvy. In the open-label ISLEND-2 trial, the figures were 0.3% for ISL/LEN and 1.3% for standard of care, Contagion Live reported.

In ISLEND-1, treatment-related adverse events occurred in 13.5% of participants on ISL/LEN and 13.2% on Biktarvy, with nausea and headache the most common in both groups. Serious adverse events were reported in 5.3% and 4.6%, and discontinuations because of adverse events were 2% and 1.7%. In ISLEND-2, treatment-related adverse events were reported in 18% of the ISL/LEN group and fewer than 1% of the standard-of-care group, a gap the investigators attributed to the open-label design, according to Contagion Live. CD4+ T-cell and lymphocyte counts were stable in both trials, and no participant stopped treatment because of a drop in those counts.

"The ISLEND-1 study results show the potential of ISL/LEN as the first once-weekly oral single-tablet treatment option," said Jürgen Rockstroh of the Department of Medicine at University Hospital Bonn, Germany, in the companies' announcement.

The trials and the drugs

Both Gilead-sponsored trials enrolled adults whose HIV had been suppressed below 50 copies/mL on a stable regimen for at least six months. Participants were randomised 1:1 to switch to ISL/LEN, with initial doses on days 1 and 2 followed by weekly dosing from day 8 to week 96, or to stay on their daily treatment. ISLEND-1 remains blinded until all participants complete week 96.

Islatravir is a nucleoside analogue that blocks HIV-1 reverse transcriptase translocation, and lenacapavir is a capsid inhibitor that acts at multiple stages of the viral lifecycle, the companies said. Participants who switched to the weekly pill in ISLEND-2 reported higher treatment satisfaction and lower treatment burden than those on daily treatment, an exploratory outcome in that open-label trial.

The combination is investigational and has not been approved by any regulator. Gilead and Merck said the ISLEND data will form the basis of regulatory submissions.