Once-Weekly Islatravir/Lenacapavir Meets Phase 3 Primary End Point

According to a new announcement from Gilead Sciences and Merck, the investigational once-weekly oral single-tablet regimen of islatravir 2 mg/lenacapavir 300 mg (ISL/LEN) maintained virologic suppression in adults with HIV who switched from standard daily antiretroviral therapy (ART), meeting the primary endpoint at Week 48 in both phase 3 ISLEND trials.¹ Detailed results will be presented for the first time at the 26th International AIDS Conference (AIDS 2026) in Rio de Janeiro, Brazil, during late-breaking sessions on July 29, 2026, and featured in the conference press program on July 21, 2026.

ISL/LEN pairs Merck’s islatravir (MK-8591), a next-generation nucleoside analog reverse transcriptase inhibitor, with Gilead’s lenacapavir, a first-in-class capsid inhibitor with activity across multiple stages of the HIV-1 life cycle.¹ Islatravir blocks HIV-1 replication through inhibition of reverse transcriptase translocation, producing both immediate and delayed chain termination. Lenacapavir disrupts HIV-1 capsid function at nuclear import, assembly, and other lifecycle stages and has no known cross-resistance to existing antiretroviral drug classes.

ISLEND-1 and ISLEND-2 trial design and 48-week virologic suppression results

ISLEND-1 (NCT06630286) is a multicenter, phase 3, randomized, double-blind, active-controlled trial evaluating ISL/LEN versus continuation of BIKTARVY (bictegravir/emtricitabine/tenofovir alafenamide; Gilead) in adults with virologically suppressed HIV-1 (RNA <50 copies/mL) on BIKTARVY for at least 6 months prior to screening.¹ Participants were randomly assigned 1:1, with ISL/LEN recipients receiving initial loading doses on Day 1 and Day 2, then once-weekly dosing from Day 8 through Week 96. The primary end point was the proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 by FDA-defined snapshot algorithm.

At Week 48, 0% of participants who switched to ISL/LEN had HIV-1 RNA ≥50 copies/mL, compared with 0.3% of those who remained on BIKTARVY, establishing noninferiority.¹ ISLEND-2 (NCT06630299) is a multicenter, phase 3, randomized, open-label, active-controlled trial evaluating ISL/LEN versus continuation of standard of care ART regimens, including integrase strand transfer inhibitor, nucleoside reverse transcriptase inhibitor, boosted protease inhibitor, and non-nucleoside reverse transcriptase inhibitor-based regimens, in virologically suppressed adults on stable therapy for at least 6 months.¹ At Week 48, 0.3% of participants receiving ISL/LEN had HIV-1 RNA ≥50 copies/mL compared with 1.3% receiving standard of care, again meeting the noninferiority threshold.

“Once-daily, combination, single-tablet antiretroviral therapy is the cornerstone of HIV treatment today. However, the treatment landscape is evolving,” Jürgen Rockstroh, MD, of the Department of Medicine, University Hospital Bonn, Germany, said in a statement.¹ “The ISLEND-1 study results show the potential of ISL/LEN as the first once-weekly oral single-tablet treatment option.”

Safety profile, treatment satisfaction, and regulatory path for ISL/LEN

In the blinded ISLEND-1 trial, treatment-related adverse events (AEs) occurred in 13.5% of participants receiving ISL/LEN and 13.2% of those continuing BIKTARVY.¹ The most common treatment-related adverse events in both groups were nausea and headache, each occurring in 3% of participants. Serious AEs were reported in 5.3% of ISL/LEN recipients and 4.6% of BIKTARVY recipients.

Discontinuations because of AEs were low at 2% for ISL/LEN and 1.7% for BIKTARVY. CD4+ T-cell counts and lymphocyte counts remained stable in both treatment groups through Week 48, and no participant discontinued because of immune cell count decreases. No clinically meaningful difference in body weight was observed between groups.¹

In the open-label ISLEND-2 trial, treatment-related AEs were reported in 18% of ISL/LEN recipients compared with fewer than 1% of those remaining on standard of care, a disparity the investigators attributed to the open-label study design.¹ The most common treatment-related AEs in the ISL/LEN group occurring in at least 2% of participants were headache (5%), nausea (3%), and diarrhea (3%). Discontinuations because of AEs were 1% for ISL/LEN and fewer than 1% for standard of care.

CD4+ T-cell counts, lymphocyte counts, and body weight remained stable in both groups through Week 48 in ISLEND-2. Participants who switched to once-weekly ISL/LEN reported higher treatment satisfaction and lower treatment burden compared with those receiving daily standard of care, as assessed by the HIV Patient Perspective of Regimen Change patient-reported outcomes instrument.¹

“Having a treatment option with once-weekly dosing can expand choice to help address individual needs and preferences,” Amy Colson, MD, research director at Community Resource Initiative and medical director of the Zinberg Clinic at Cambridge Health Alliance, said in a statement.¹ “The 48-week findings provide the evidence for ISL/LEN as the potential first once-weekly oral treatment option to help support long-term treatment needs and be responsive to the preferences of people living with HIV.”

Islatravir and lenacapavir in combination are investigational and have not been approved for use by any regulatory authority. Gilead and Merck stated these data will form the basis of regulatory submissions.¹ There is currently no cure for HIV or AIDS.

References

1. Gilead Sciences, Inc. and Merck & Co., Inc. Investigational once-weekly oral HIV treatment regimen of islatravir and lenacapavir maintained virological suppression in adults with HIV who switched antiretroviral therapy. Published July 20, 2026. Accessed July 21, 2026. https://www.businesswire.com/news/home/20260720061462/en/Investigational-Once-Weekly-Oral-HIV-Treatment-Regimen-of-Islatravir-and-Lenacapavir-Maintained-Virological-Suppression-in-Adults-With-HIV-Who-Switched-Antiretroviral-Therapy