Detailed phase 3 findings from the Islend clinical program indicate that a once-weekly tablet combining Gilead Sciences’ lenacapavir and Merck & Co.’s islatravir performed comparably to established daily HIV treatments in maintaining viral suppression through 48 weeks. The results, scheduled for presentation at the 26th International AIDS Conference in Rio de Janeiro, suggest the regimen could become the first complete weekly oral treatment for HIV.
The Islend-1 study enrolled 607 participants whose HIV infection was already well controlled with Gilead’s daily treatment Biktarvy. By Week 48, none of the participants who switched to the weekly islatravir/lenacapavir (ISL/LEN) regimen had HIV RNA levels of 50 copies/mL or higher. In comparison, one participant, representing 0.1% of those who remained on Biktarvy, met that threshold. Average CD4+ T-cell counts declined by 10 cells/μL in the ISL/LEN group and by 18 cells/μL among those who continued Biktarvy. Participants entered the study with CD4 counts of approximately 740 cells/μL, above the 500 cells/μL threshold considered normal.
The second phase 3 trial, Islend-2, included 626 individuals whose HIV was suppressed using a variety of daily oral regimens. At Week 48, one participant receiving ISL/LEN and four participants continuing standard therapies recorded HIV RNA levels of at least 50 copies/mL. Changes in CD4 counts differed between the groups, with an average decline of 45 cells/μL in the weekly-treatment arm and 8 cells/μL in the control group. Researchers noted that participants receiving ISL/LEN began the study with higher baseline CD4 counts and that values between the groups became more similar by Week 48.
Attention has previously focused on islatravir’s effects on immune-cell counts after the U.S. Food and Drug Administration placed several Merck studies on clinical hold in 2021 following declines in total lymphocyte and CD4 T-cell counts in some patients. According to Jared Baeten, M.D., Ph.D., Gilead’s clinical development lead in virology, those findings were associated with substantially higher doses than those used in the Islend trials. Investigators reported no differences between treatment groups in lymphocyte counts at Week 48 in either study.
Safety outcomes were generally similar between the weekly regimen and daily oral therapies. Treatment-emergent adverse events of any grade occurred in the high-70% range across all study groups. In Islend-1, treatment-related adverse events of any grade were reported in 13.5% of participants receiving ISL/LEN and 13.2% of those receiving Biktarvy. In Islend-2, the corresponding figures were 18.5% for ISL/LEN and 0.3% for the control arm. Serious treatment-related adverse reactions and treatment discontinuations linked to treatment remained uncommon across both trials.
Discussing the potential role of the regimen, Baeten said, “Many people living with HIV struggle with adherence.” He said that once-weekly pills reduce the psychological challenges of HIV adherence from seven days a week to one and described the regimen as another treatment option alongside existing approaches such as daily oral therapies and long-acting injectable regimens.
The positive treatment results come as Gilead continues to advance lenacapavir-based programs. The company is launching two phase 3 Daybreak studies evaluating lenacapavir in combination with the broadly neutralizing antibodies teropavimab and zinlirvimab. At the same conference, Gilead also reported updated data from the Purpose trials of Yeztugo, its twice-yearly lenacapavir injection for HIV prevention.
In the open-label extension phases, 95% of eligible participants in both Purpose 1 and Purpose 2 chose to start or continue Yeztugo. No HIV infections were reported among participants using Yeztugo in the Purpose 1 extension, while one infection occurred in the Purpose 2 extension among an individual who received all injections on schedule.
Meanwhile, Merck recently secured FDA approval for islatravir in combination with doravirine as the daily HIV treatment Idvynso. The company is also developing alimatravir as a potential once-monthly oral pre-exposure prophylaxis option and is studying a separate once-weekly treatment combination pairing islatravir with ulonivirine in phase 2 testing.
Lenacapavir and Islatravir have reached an important milestone after Gilead Sciences and Merck announced positive Phase 3 clinical trial results for their investigational once-weekly oral HIV treatment. The successful study demonstrates the potential of this innovative combination therapy to provide people living with HIV a more convenient alternative to traditional daily antiretroviral medications.
Lenacapavir and Islatravir Achieve Positive Phase 3 Results
The Phase 3 trial evaluated Lenacapavir and Islatravir as a once-weekly oral regimen in adults with virologically suppressed HIV-1 infection. The study met its primary endpoint by demonstrating that the weekly treatment maintained viral suppression while showing a safety profile comparable to existing HIV therapies. These findings support the continued development of the regimen as a potential new treatment option.
