Once-Weekly HIV Pill Matches Daily Treatment in Phase 3 Trials

A once-weekly oral HIV treatment combining islatravir and lenacapavir matched the effectiveness of daily antiretroviral regimens in two Phase 3 clinical trials, according to results presented at the 26th International AIDS Conference and published in the New England Journal of Medicine.

Gilead Sciences and Merck developed the single-tablet combination, pairing islatravir, a next-generation nucleoside analog, with lenacapavir, a first-in-class capsid inhibitor. The pharmacokinetic profiles of both drugs allow for once-weekly dosing.

The Phase 3 program included two trials, ISLEND-1 and ISLEND-2, both enrolling adults who had been virologically suppressed for at least six months.

ISLEND-1 compared the once-weekly pill to BIKTARVY, a daily single-tablet regimen. At week 48, 93.4 percent of participants taking the once-weekly pill maintained viral suppression, compared to 92.4 percent in the BIKTARVY group. No participants in the once-weekly arm had HIV-1 RNA levels at or above 50 copies per milliliter.

ISLEND-2 compared the once-weekly pill to various daily standard-of-care regimens. At week 48, 95.2 percent of those switching to the once-weekly pill maintained viral suppression, compared to 95.5 percent of those staying on daily regimens. Virologic failure occurred in 0.3 percent of the once-weekly group versus 1.3 percent in the standard-of-care group.

Safety profiles were comparable to daily comparator regimens in both trials. Headache, nausea, and diarrhea were the most frequently reported side effects. Unlike earlier studies of higher-dose islatravir that were halted due to declines in CD4 cell counts, the 2 mg dose used in these trials did not produce such decreases.

Participants in ISLEND-2 reported higher treatment satisfaction and a lower sense of treatment burden compared to their previous daily regimens. Gilead and Merck plan to use the data to support regulatory submissions worldwide.