A Phase III switch study occurring over 96 weeks has demonstrated that Merck’s doravirine/islatravir (DOR/ISL) sustains durable viral suppression with stable safety outcomes in virologically suppressed adults with HIV, reinforcing momentum behind two-drug single-tablet regimens (STR). The data positions DOR/ISL as a credible integrase-sparing challenger in a market recalibrating toward simplified, lower-toxicity maintenance strategies ahead of anticipated US launch in 2026, says GlobalData, a leading intelligence and productivity platform.

The randomized study enrolled 551 adults, with 366 participants switching to DOR/ISL at baseline and 185 continuing their existing oral antiretroviral therapy (ART) regimen. At week 48, nearly all participants remaining on baseline therapy changed over to DOR/ISL, resulting in a total of 543 individuals receiving the investigational regimen.  

Anaelle Tannen, Infectious Disease Analyst at GlobalData, comments: “This once-daily, two-drug STR regimen offers an integrase-sparing alternative to ViiV Healthcare’s Dovato, one of the leading STRs currently on the market.”

DOR/ISL is currently at the pre-registration stage of development in the US and is expected to launch in this market in 2026, if approved.  It is also in Phase III development in the EU. The safety outcomes from the Phase III trial remained consistent with earlier findings. The rates of adverse events during weeks 48 to 96 were comparable to those seen in the first 48 weeks of treatment.

Importantly, the 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 the 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.

Tannen continues: “The market is shifting away from 3-or-4 drug STRs, which currently dominate the market, towards 2-drug STRs in the pipeline, with the aim of simplifying treatment, and reducing drug exposure and toxicity, and DOR/ISL is one such example”.

While virologic suppression data has been promising for DOR/ISL, the key opinion leaders (KOLs) interviews by GlobalData note that to justify its use, the combination must demonstrate reduced side effects compared to standard-of-care drugs like Biktarvy, particularly regarding weight gain and central nervous system (CNS) tolerability. Its appeal may be strongest among patients with previous integrase inhibitor intolerance or metabolic concerns. GlobalData projects the drug could reach around $1.8 billion by 2033, across the 7MM*.  

Tannen concludes: “If approved, DOR/ISL’s commercial trajectory will hinge on payer positioning and its ability to differentiate beyond non-inferiority, particularly in weight, CNS tolerability, and long-term resistance data. As treatment-experienced populations age, demand for metabolically neutral, switch-friendly regimens will intensify, creating targeted but meaningful market expansion opportunities.”

*7MM: The US, France, Germany, Italy, Spain, the UK, and Japan.