Lancet (new data): Switch to fixed-dose doravirine (100 mg) and islatravir (0·25 mg) once daily in virologically suppressed adults with HIV-1 on oral antiretroviral therapy: 48-week results of a phase 3, multicentre, randomised, OL, non-inferiority trial

This phase 3, randomized, open-label, non-inferiority trial evaluated the efficacy and safety of switching virologically suppressed adults living with HIV‑1 from stable oral antiretroviral therapy (ART) to a once-daily, fixed-dose combination of doravirine (100 mg) and islatravir (0.25 mg). The study was conducted across 53 sites in eight countries and enrolled adults with sustained viral suppression and no prior treatment failure or resistance.

Participants were randomized 2:1 to either switch to doravirine/islatravir or continue their baseline ART for 48 weeks. The primary endpoint was the proportion of participants with HIV‑1 RNA ≥50 copies/mL at week 48.

Doravirine and islatravir demonstrated non-inferiority to baseline ART, with fewer participants experiencing virologic failure at week 48 (1.4% vs 4.9%). Although treatment-related adverse events were more frequent in the doravirine/islatravir group, overall rates of adverse events, serious adverse events, and treatment discontinuations were comparable between groups. No clinically relevant declines in CD4 or total lymphocyte counts were observed, and no deaths were considered treatment-related.

Overall, doravirine and islatravir was effective and well tolerated and may represent the first non-INSTI-based, two-drug, single-tablet regimen for HIV‑1 treatment. Given concerns about emerging integrase inhibitor resistance, this regimen could provide an important alternative for patients requiring a switch in therapy and supports the continued development of islatravir, including its long-acting potential.

Additional information to the following link: Switch to fixed-dose doravirine (100 mg) and islatravir (0·25 mg) once daily in virologically suppressed adults with HIV-1 on oral antiretroviral therapy: 48-week results of a phase 3, multicentre, randomised, open-label, non-inferiority trial - The Lancet