Doravirine/islatravir (100/0.75 mg) once-daily compared to bictegravir/emtricitabine/tenofovir alafenamide as initial HIV-1 treatment: 48-week results from a phase 3, randomized, controlled, double-blind, non-inferiority trial.

Background: Doravirine/islatravir is an investigational, once-daily regimen being studied for HIV-1 treatment.

Methods: In this phase 3, double-blind, non-inferiority trial, previously untreated people with HIV-1 (≥18 years) were randomized (1:1) and stratified by HIV-1 RNA (≤/>100,000 copies/mL) and CD4 count (

Results: 597 participants were randomized and treated; enrollment stopped early due to decreases in CD4 and lymphocyte counts observed in other islatravir studies. At week 48, doravirine/islatravir (100/0.75 mg) was non-inferior to bictegravir/emtricitabine/tenofovir alafenamide: 265/298 (88.9%) versus 264/299 (88.3%) had HIV-1 RNA 50 copies/mL (difference 0.5%, 95%CI -4.7 to 5.6). Mean change from baseline in CD4 count was +182 and +234 cells/µL (difference -50, 95%CI -79 to -21) with doravirine/islatravir versus bictegravir/emtricitabine/tenofovir alafenamide. Mean change in lymphocyte count was 0.01 and 0.21 x 109/L (difference -0.20, 95%CI -0.30 to -0.10). Adverse events (AEs) occurred in 90.6% and 87.3% of participants, with COVID-19 being the most common (14.1%, 16.4%). Treatment-related AEs were similar (28.9%, 25.8%). AEs leading to discontinuations were higher with doravirine/islatravir (8.7%, 3.7%) due to protocol-specified criteria requiring discontinuation for decreased CD4 and lymphocyte counts.

Conclusion: 597 participants were randomized and treated; enrollment stopped early due to decreases in CD4 and lymphocyte counts observed in other islatravir studies. At week 48, doravirine/islatravir (100/0.75 mg) was non-inferior to bictegravir/emtricitabine/tenofovir alafenamide: 265/298 (88.9%) versus 264/299 (88.3%) had HIV-1 RNA 50 copies/mL (difference 0.5%, 95%CI -4.7 to 5.6). Mean change from baseline in CD4 count was +182 and +234 cells/µL (difference -50, 95%CI -79 to -21) with doravirine/islatravir versus bictegravir/emtricitabine/tenofovir alafenamide. Mean change in lymphocyte count was 0.01 and 0.21 x 109/L (difference -0.20, 95%CI -0.30 to -0.10). Adverse events (AEs) occurred in 90.6% and 87.3% of participants, with COVID-19 being the most common (14.1%, 16.4%). Treatment-related AEs were similar (28.9%, 25.8%). AEs leading to discontinuations were higher with doravirine/islatravir (8.7%, 3.7%) due to protocol-specified criteria requiring discontinuation for decreased CD4 and lymphocyte counts.