Safety and Efficacy of Doravirine/Islatravir (100 mg/0.25 mg) Once Daily after Islatravir Dose Reduction from 0.75 mg: Week 96 Results from an Open-Label Phase 3 Study in Adults with HIV-1.

Abstract

Background: Once-daily doravirine/islatravir (DOR/ISL 100 mg/0.25 mg) demonstrated non-inferior efficacy and comparable safety to continuing prior antiretroviral therapy in two phase 3 studies of virologically suppressed adults with HIV-1. We assessed the safety and efficacy of DOR/ISL (100 mg/0.25 mg) in participants who received ISL (0.75 mg) in previous clinical studies.

Methods: In this phase 3, open-label, single-arm study (NCT05766501), adults with HIV-1 RNA <200 copies/mL while receiving DOR/ISL (100 mg/0.75 mg) switched to DOR/ISL (100 mg/0.25 mg). Primary objectives were the safety and tolerability of DOR/ISL through week 96. Secondary objectives included antiretroviral activity (FDA snapshot approach) and changes in total lymphocyte and CD4+ T-cell counts.

Results: 639 participants were treated: 69.3% were male, 55.7% White, median age 44.0 (range 20-79) years, and median time on DOR/ISL before enrollment 2.7 years. By week 96, 559 participants (87.5%) reported adverse events, which were considered drug-related in 19 (3.0%). Six participants (0.9%) discontinued due to adverse events, one of which was considered drug-related. At week 96, HIV-1 RNA was <50 copies/mL in 589 participants (92.2%) and ≥50 copies/mL in 6 (0.9%). Three participants (0.5%) had confirmed HIV-1 RNA ≥200 copies/mL; resistance results were not available due to assay failure. Mean increases from day 1 (of the current study) were 16.2% for total lymphocyte count and 18.1% for CD4+ T-cell count.

Conclusions: Once-daily DOR/ISL (100 mg/0.25 mg) demonstrated favorable safety and tolerability through week 96 and maintained virologic suppression in >92% of participants. DOR/ISL remained effective and well-tolerated for over 4.5 years.