Weekly HIV Pill Advances Toward Regulatory Submission
A combination therapy from Gilead and Merck has met its clinical efficacy endpoint, demonstrating non-inferiority to existing daily treatments with no new safety concerns identified in treatment-experienced patient population.
Gilead Sciences and Merck have announced positive topline results from two Phase III studies evaluating islatravir/lenacapavir as an investigational oral once-weekly treatment for HIV. Both ISLEND-1 and ISLEND-2 trials met their primary efficacy endpoints at week 48, marking a key milestone in the development of a long-acting oral HIV therapy that can be taken weekly rather than daily.
The investigational combination therapy pairs two novel mechanisms of action that disrupt HIV at multiple stages of its lifecycle: Merck's islatravir is a next-generation nucleoside analog, while Gilead's lenacapavir represents a first-in-class capsid inhibitor. This dual approach offers a scientifically distinct alternative to existing HIV treatments and could provide patients with a lower frequency dosing schedule.
In the clinical studies, the combination treatment was evaluated in adults who were already virologically suppressed with HIV-1 RNA levels below 50 copies/mL and were switching from existing treatment. The clinical data gained from the trails, demonstrated that the once-weekly single-tablet regimen was statistically non-inferior to current standard treatments with no new safety concerns identified. Throughout the double-blind ISLEND-1 study, the regimen performed comparably to BIKTARVY, the widely used daily pill treatment. The open-label ISLEND-2 trial similarly showed that the once-weekly option was non-inferior to standard-of-care daily oral antiretroviral therapy.
“Long-acting oral therapies represent a new wave of transformational innovation in HIV drug development, with the potential to reshape the landscape of care,” said Jared Baeten, MD, PhD, Senior Vice President, Clinical Development, Virology Therapeutic Area Head, Gilead Sciences, in a company press release (1). “Innovative oral HIV treatment options that allow for less frequent dosing may make a meaningful difference in the lives of people living with the virus, potentially offering more flexibility and discretion.”
“These results underscore the shared focus and commitment that we and our collaborators at Gilead have on continuing research to help people living with HIV,” added Dr. Eliav Barr, Senior Vice President, Head of Global Clinical Development and Chief Medical Officer, Merck Research Laboratories, in the press release (1). “By advancing this investigational novel once-weekly oral regimen of islatravir and lenacapavir, we aim to bring forward a new long-acting oral option that, if approved, would represent the first of its kind with less frequent dosing and further expand options for people living with HIV.”
The companies plan to file the Phase III data with global regulatory authorities in the coming months and will also present the findings at a future scientific congress. Regulatory submissions will include comprehensive efficacy and safety data from both ISLEND-1 and ISLEND-2 trials to support potential approval of the once-weekly regimen for treatment-experienced adults with suppressed HIV.
If approved, islatravir/lenacapavir could significantly improve quality of life and potentially enhance adherence for individuals living with HIV. The investigational combination remains not yet approved, and the companies continue working toward bringing this potential treatment to patients who could benefit from the reduced dosing frequency.
Reference
Gilead. Gilead and Merck Announce Positive Topline Results From Two Phase 3 Studies Evaluating Islatravir/Lenacapavir, an Oral Once-Weekly HIV Treatment. Press Release, June 8, 2026.