Once-Weekly HIV Pill Meets Non-Inferiority Targets in Twin Phase 3 Trials

Preliminary Week 48 results from ISLEND-1 and ISLEND-2 show the oral islatravir/lenacapavir combination held its own against daily standard-of-care regimens — but full data, safety details, and a regulatory timeline are not yet public.

Gilead Sciences and Merck have announced that their investigational once-weekly oral HIV regimen — islatravir combined with lenacapavir — met its primary non-inferiority endpoint against daily standard-of-care therapy at Week 48 in both ISLEND-1 and ISLEND-2, the twin Phase 3 trials designed to support a regulatory submission for virologically suppressed adults with HIV-1.

The Trials

ISLEND-1 (NCT06630286) and ISLEND-2 (NCT06630299) are double-blind, double-dummy randomized controlled trials enrolling adults whose HIV-1 is virologically suppressed on a stable daily antiretroviral regimen. Participants were randomized to once-weekly islatravir/lenacapavir or to continue their existing daily therapy — primarily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or equivalent. The primary endpoint in both trials is the proportion of participants with HIV-1 RNA at or above 50 copies/mL at Week 48 (the virologic failure rate per the FDA Snapshot algorithm); non-inferiority is demonstrated when this failure rate is no worse in the experimental arm.

Both Gilead and Merck announced that preliminary Week 48 results met the pre-specified non-inferiority margin. The announcement is consistent with Phase 2 data (PMC11777299), which showed 94.2% virologic suppression with once-weekly islatravir/lenacapavir versus 92.3% with daily B/F/TAF — though Phase 2 sample sizes are smaller and enrollment criteria differ.

What Remains Undisclosed

The sponsor announcements did not include actual Week 48 suppression rates, confidence interval widths, the number of virologic failures in each arm, resistance emergence data, or detailed safety findings. Full data are expected to be presented at an upcoming scientific conference; no conference or regulatory submission timeline has been specified.

A once-weekly oral pill would meaningfully reduce the daily treatment burden for many people living with HIV. Daily therapy is highly effective for adherent patients, but real-world adherence is imperfect. A weekly schedule also offers an alternative to the injectable long-acting regimens that require clinic visits for administration.

Why This Combination

Islatravir is a nucleoside reverse transcriptase translocation inhibitor (NRTTI); lenacapavir is a capsid inhibitor. The two drugs target distinct steps in the HIV replication cycle with complementary mechanisms and non-overlapping resistance profiles. Lenacapavir is already approved as a twice-yearly injectable (Sunlenca) for heavily treatment-experienced patients.

Gilead Sciences and Merck ISLEND-1/2 topline announcements, June 2026. NCT06630286, NCT06630299 (ClinicalTrials.gov). PMC11777299 (Phase 2 reference data).

Correction (June 21, 2026): An earlier version of this article stated the primary non-inferiority endpoint was “HIV-1 RNA <50 copies/mL at Week 48.” Per Gilead and Merck topline announcements and ClinicalTrials.gov records, the primary efficacy endpoint in both ISLEND-1 and ISLEND-2 was the proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 per the FDA Snapshot algorithm — the virologic failure rate, not the virologic success rate. The front-matter claim and body text have been corrected.

Trace · every claim, sourced

Reported and written by Dr. Priya Raman, Clinical Trials Desk, then each load-bearing claim was bound to the primary source it rests on and checked out-of-band against that source before publication. The full mapping is below — nothing here is taken on faith.

ISLEND-1 and ISLEND-2 both met their primary non-inferiority endpoint for HIV-1 RNA ≥50 copies/mL at Week 48 per the FDA Snapshot algorithm versus daily antiretroviral therapy, per sponsor topline announcements.

press_release Gilead Sciences — ISLEND-1 Phase 3 Week 48 topline results, June 2026 gilead-bw-islend-1-week48-june2026

Full Week 48 data including actual suppression rates, confidence intervals, and safety detail have not been publicly disclosed as of publication.

press_release Merck — ISLEND-2 Phase 3 Week 48 topline results, June 2026 merck-pr-islend-2-week48-june2026

Phase 2 data showed 94.2% virologic suppression with once-weekly islatravir/lenacapavir versus 92.3% with daily B/F/TAF at Week 48 (PMC11777299) — Phase 3 rates not yet available.

journal_article Phase 2 islatravir/lenacapavir weekly in HIV-1 — PMC11777299

After publication, a separate AI panel re-verifies every edition against these same sources. The running claim-confirmation rate and every correction are public on the accuracy ledger.