In April 2026, the US Food and Drug Administration (FDA) approved a new, two-drug single-tablet regimen containing doravirine and islatravir for the treatment of HIV-1 infection in adults. The combination is marketed as Idvynso® and is licensed to replace the current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen, with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine.
Islatravir is a nucleoside reverse transcriptase inhibitor (NRTI) and is not significantly metabolized by CYP enzymes but is primarily metabolized by adenosine deaminase (~53%). It requires phosphorylation by deoxycytidine kinase to form the pharmacologically active islatravir triphosphate.
The interaction profile of doravirine/islatravir (DOR/ISL) is similar to that of doravirine alone, but with additional contraindicated/not recommended comments for lamivudine or emtricitabine, deoxycytidine kinase substrates (i.e., cladribine, clofarabine, cytarabine, fludarabine, gemcitabine) and adenosine deaminase inhibitors (i.e., pentostatin). Coadministration with lamivudine, emtricitabine or deoxycytidine kinase substrates may decrease the effectiveness of doravirine/islatravir due to decreased intracellular concentrations of islatravir triphosphate. In contrast, coadministration with adenosine deaminase inhibitors may increase plasma concentrations of islatravir.
Full details regarding the use of doravirine/islatravir are available in the Idvynso Prescribing Information from Merck (or alternatively from the FDA as the Merck website is geo-blocked for some locations).
Doravirine/islatravir has been added to the interaction checker on the website and iChart app. The NNRTI interaction summary chart has been updated to include doravirine/islatravir as an HIV therapy and it is listed as a comedication on the other interaction summary charts. A pharmacokinetic fact sheet for islatravir has also been added.
