In a phase 3 study of virologically suppressed adults with HIV, switching to once-daily doravirine/islatravir (DOR/ISL 100/0.25 mg) maintained high rates of viral suppression through 96 weeks, with no emergent resistance and a favorable safety profile.
New 96-week data from the open-label, phase 3 MK-8591A-051 study demonstrate that switching to the fixed-dose combination of doravirine and islatravir (DOR/ISL) continues to support durable viral suppression and long-term tolerability in adults with HIV who were previously virologically suppressed on oral antiretroviral therapy (ART).
The randomized study enrolled 551 adults, with 366 participants switching to DOR/ISL at baseline and 185 continuing their existing ART regimen. At week 48, nearly all participants remaining on baseline therapy crossed over to DOR/ISL, resulting in a total of 543 individuals receiving the investigational regimen. Participants had lived with HIV for a median of more than 13 years, and baseline regimens included integrase inhibitor–, NNRTI-, and protease inhibitor–based therapies.
At Week 96, virologic suppression remained high across both groups. HIV RNA levels of at least 50 copies/mL were observed in fewer than 2% of participants, while more than 92% maintained viral suppression. Only one participant met criteria for clinically significant confirmed viremia after switching to DOR/ISL, and no treatment-emergent resistance to either doravirine or islatravir was detected through 96 weeks.
More than 92% of participants maintained viral suppression through 96 weeks after switching to DOR/ISL.
No treatment-emergent resistance to doravirine or islatravir was observed through two years of follow-up.
DOR/ISL was well tolerated, with stable lymphocyte counts and modest weight changes overall.
Safety outcomes remained consistent with earlier findings. Rates of adverse events during weeks 48 to 96 were comparable to those seen in the first 48 weeks of treatment. Importantly, mean changes in CD4+ T-cell counts and total lymphocyte counts were similar across treatment groups, with no discontinuations attributed to declines in immune cell levels.
Weight changes following initiation of DOR/ISL were modest overall. Larger increases were observed among participants who switched from regimens containing efavirenz and/or tenofovir disoproxil fumarate, consistent with prior observations of weight changes following discontinuation of weight-suppressive therapies.
Together, the 96-week results reinforce DOR/ISL as a potential option for people with HIV who are virologically suppressed on existing oral ART.
