Once-Weekly Oral Islatravir Plus Lenacapavir Versus Daily Oral Bictegravir, Emtricitabine, and Tenofovir Alafenamide in Persons With HIV-1 : A Phase 2 Randomized Study

Abstract

Background: Once-weekly oral islatravir plus lenacapavir (ISL+LEN) has the potential to address adherence challenges with daily HIV-1 treatment.

Objective: To evaluate efficacy and safety of once-weekly ISL+LEN.

Design: Phase 2, randomized, open-label, active-controlled study. (ClinialTrials.gov: NCT05052996).

Setting: 44 U.S. sites.

Participants: Adults with HIV-1 RNA viral load of less than 50 copies/mL receiving daily bictegravir, emtricitabine, and tenofovir alafenamide combination (B/F/TAF) for 24 weeks or more.

Intervention: Once-weekly oral ISL, 2 mg, plus LEN, 300 mg, or daily oral B/F/TAF.

Measurements: Proportion with HIV-1 RNA viral load of 50 copies/mL or more at week 24 (primary end point; U.S. Food and Drug Administration Snapshot Algorithm). Secondary end points: proportion of participants with HIV-1 RNA viral load of 50 copies/mL or more (weeks 12 and 48) and HIV-1 RNA viral load of less than 50 copies/mL (weeks 12, 24. and 48), safety, and CD4⁺ T-cell and lymphocyte count changes (weeks 12, 24, and 48).

Results: A total of 104 participants were randomly assigned and treated (n = 52 per group). At week 24, one ISL+LEN participant and no B/F/TAF participants had HIV-1 RNA viral load of 50 copies/mL or more (difference, 1.9% [95% CI, -5.2% to 10.5%]); 94.2% of participants in both groups had HIV-1 RNA viral load of less than 50 copies/mL (difference, 0% [CI, -10.9% to 10.9%]). At week 48, 94.2% and 92.3% of ISL+LEN and B/F/TAF participants, respectively, had HIV-1 RNA viral load of less than 50 copies/mL (difference, 1.9% [CI, -9.3% to 13.6%]); no participant had HIV-1 RNA viral load of 50 copies/mL or more. Two ISL+LEN participants discontinued treatment (before week 24) due to adverse events (AEs) unrelated to the study drug. No AEs that were grade 3 or greater or serious were related to treatment in either group. Changes in CD4⁺ T-cell and lymphocyte counts from baseline to week 48 were similar between groups, with no discontinuations of study drug treatment due to decreased CD4⁺ T cells or lymphocytes.

Limitation: Open-label, modest sample size, and only U.S.-based participants.

Conclusion: Once-weekly oral ISL+LEN maintained high rates of virologic suppression through week 48 and was not associated with any treatment-related grade 3 or greater or serious AEs.

Primary funding source: Gilead Sciences, Inc.