Gilead's weekly islatravir/lenacapavir beats standard HIV care at Week 48
ISLEND-2 topline data show 0.3% virologic failure on the oral weekly regimen versus 1.3% on daily standard of care, with full results due at AIDS 2026 on July 29.
Executive Summary
- A Phase 3 trial testing an oral, once-weekly two-drug regimen against daily standard-of-care therapy in people with HIV who are already virologically suppressed met its primary endpoint at Week 48, with fewer participants on the weekly regimen showing detectable virus than on daily therapy.
- The result, corroborated by a matching primary-endpoint win in the trial's companion study, gives the sponsors a basis to move toward regulatory filings for a lower-frequency oral option in a population that currently manages HIV with daily pills.
- Full effect-size detail, confidence intervals, and the complete safety comparison are due at a late-breaking scientific session before the end of July, which will determine how the topline non-inferiority margin holds up under closer scrutiny.
- The regimen enters a field where oral therapy is well established across several mechanisms, and its distinguishing feature is dosing frequency rather than a new mechanism, competing on convenience against daily pills and longer-acting injectable regimens already in Phase 3 testing.
The readout
ISLEND-2, a 600-patient Phase 3 trial, tested whether switching virologically suppressed adults with HIV-1 from daily standard-of-care antiretroviral therapy to an oral, once-weekly regimen of islatravir and lenacapavir could hold viral suppression as well as daily treatment. The registered primary endpoint was the proportion of participants with HIV-1 RNA at or above 50 copies per milliliter at Week 48, measured by the FDA's Snapshot Algorithm. Gilead Sciences and Merck disclosed that the endpoint was met: 0.3% of participants on the weekly regimen crossed that threshold, versus 1.3% on daily standard of care, and the safety profile was described as generally similar between arms with no new safety concerns identified. Full data, including secondary endpoints and safety detail, are scheduled for a late-breaking session at AIDS 2026 in Rio de Janeiro on July 29. NCT06630299+1Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1NCT06630299Gilead to Present New HIV Research at AIDS 2026 Across Prevention, Treatment and CureJul 21, 2026
Probability of SuccessBased on the AppliedXL Probability of Success model. For more information about the methodology, read the research here.
Why it matters
"Progress against the HIV epidemic requires both scientific innovation and enduring partnerships with communities around the world," said Jared Baeten, MD, PhD, Gilead's senior vice president of clinical development and virology therapeutic area head, in the company's announcement of its AIDS 2026 program. For people who are already suppressed on daily antiretroviral therapy, a weekly oral option would cut dosing frequency without requiring a switch to an injectable, and the companion Phase 3 trial, ISLEND-1, also met its Week 48 primary endpoint in a separate population of suppressed patients, corroborating the result across two studies. The sponsors said the Week 48 data from both trials will form the basis of regulatory submissions, though no application timing or reviewing authority has been specified. Gilead+1Gilead to Present New HIV Research at AIDS 2026 Across Prevention, Treatment and CureJul 21, 2026Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1NCT06630299
Operational picture
ISLEND-2 finished enrolling on target at 600 participants and moved to active, not recruiting status in May 2025 once enrollment closed. Its primary completion date moved twice, first pulled in from June 2027 to April 2026 in July 2025, then adjusted to April 23, 2026 in May 2026, a net acceleration rather than a delay, and the trial's full completion date remains set out to August 2030 to capture longer-term secondary endpoints through Week 96. NCT06630299Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1NCT06630299
Competitive positioning
Islatravir shares its nucleoside reverse transcriptase translocation inhibitor mechanism with Merck's earlier islatravir combination programs, including a Phase 2 trial pairing islatravir with doravirine, the closest mechanism-level comparator on record. The broader HIV-1 field is small and not expanding: 48 recent trials in HIV-1 x HIV-1 Infection compare against 528 older ones, and only two trials are currently active in that specific target-indication pairing. Named oral competitors include Gilead's own bictegravir-based regimens and Merck's doravirine, alongside ViiV Healthcare's cabotegravir and dolutegravir programs, all competing primarily on dosing convenience and switch eligibility rather than a distinct mechanism. Merck's doravirine/islatravir combination, sold as IDVYNSO, is already approved for HIV-1 treatment in adults, giving the class a regulatory precedent for a two-drug oral switch regimen that ISLEND-2's weekly dosing format would extend. NCT06630299+1Study to Compare an Oral Weekly Islatravir/Lenacapavir Regimen With Standard of Care in Virologically Suppressed People With HIV-1NCT06630299Gilead to Present New HIV Research at AIDS 2026 Across Prevention, Treatment and CureJul 21, 2026
This analysis was produced using AI-assisted reporting systems, AppliedXL data, and official public records. These systems undergo editorial review, quality checks, and regular audits by human experts. Errors may still occur, as with any automated system. Always consult the linked primary sources. Read our AI Editorial Policy.