Doravirine/islatravir for the hardest-to-treat: results in heavily treatment-experienced HIV-1 patients

For people living with HIV-1 who have exhausted their treatment options — those with extensive multidrug resistance and few active drugs left — building an effective regimen is one of the toughest challenges in HIV care. This randomised phase 3 trial tested whether adding the fixed-dose combination doravirine/islatravir (DOR/ISL) to optimised background therapy could help. Across 35 heavily treatment-experienced adults, most with triple-class resistance, DOR/ISL plus baseline ART drove a meaningful drop in viral load within just eight days, and by week 49, 71% of participants had achieved viral suppression below 50 copies/mL, alongside a mean CD4+ T-cell recovery. The combination was generally well tolerated, though the study — cut short by a clinical hold tied to lymphocyte concerns at higher islatravir doses — also surfaces important questions about dosing in this vulnerable population.