The FDA has approved doravirine/islatravir (Idvynso; Merck), a once-daily, oral, 2-drug fixed-dose combination tablet for the treatment of HIV-1 infection in adults who are virologically suppressed on a stable antiretroviral regimen with no history of virologic treatment failure and no known resistance substitutions to doravirine. The approval makes doravirine/islatravir the first non-integrase strand transfer inhibitor (INSTI), tenofovir (Viread; Gilead Sciences)-free 2-drug regimen to demonstrate non-inferior efficacy to a 3-drug standard regimen—including the widely used bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF; Biktarvy)—in a head-to-head phase 3 trial. The drug will be available in pharmacies after May 11, 2026.1
The regimen combines doravirine (100 mg), a non-nucleoside reverse transcriptase inhibitor (NNRTI) with an established efficacy and safety profile, with islatravir (0.25 mg), the first approved nucleoside analog reverse transcriptase inhibitor (NRTI)—a first-in-class mechanism that blocks HIV replication through multiple pathways, including both immediate and delayed chain termination of viral DNA synthesis. The dual mechanism of islatravir distinguishes it from conventional NRTIs and was a central reason for its development as an anchor agent for simplified two-drug regimens.1
Phase 3 Evidence Supporting the Approval
The approval is supported by week 48 data from 2 randomized, active-controlled, non-inferiority trials in virologically suppressed adults. In Trial 052 (NCT05630755), a double-blind study in which participants were switched from BIC/FTC/TAF to doravirine/islatravir, 1% of the doravirine/islatravir group (n=342) had a viral load at or above 50 copies/mL at week 48 versus 1% in the BIC/FTC/TAF group (n=171; treatment difference 0.9%; 95% CI, –1.9% to 2.9%), meeting non-inferiority criteria. Secondary endpoint data showed 92% of doravirine/islatravir recipients maintained virologic suppression (HIV-1 RNA below 50 copies/mL) at week 48 compared to 94% remaining on BIC/FTC/TAF.1
In Trial 051 (NCT05631093), an open-label study in which participants switched from a range of oral antiretroviral therapy (ART) regimens, including INSTI-based (64%), protease inhibitor-based (5%), and other regimens (30%), virologic failure at or above 50 copies/mL occurred in 1% of doravirine/islatravir recipients (n=366) versus 5% of those remaining on their baseline ART (n=185; treatment difference –3.6%; 95% CI, –7.8% to –0.8%). At week 48, 96% of participants switched to doravirine/islatravir and maintained viral suppression compared to 92% on baseline ART. The combined trials enrolled 708 participants who received doravirine/islatravir, including 81 (11%) aged 65 years and older—a notable proportion given the growing clinical focus on the aging HIV population. Treatment outcomes were consistent across age, sex, and race subgroups.1
Extended data from CROI 2026 reinforced the week 48 findings: at week 96 in Trial 051, 96.6% of participants who switched from baseline ART to doravirine/islatravir at week 48 maintained virologic suppression, with low rates of adverse event-related discontinuations and no clinically meaningful changes in total lymphocyte or CD4 T-cell counts over time.2
Why This Approval Matters Clinically
The importance of doravirine/islatravir extends beyond its mechanistic novelty. As people living with HIV live longer on effective ART, managing comorbidities and long-term drug toxicities has become an increasingly pressing challenge. People with HIV experience accelerated biological aging and face disproportionately high rates of chronic kidney disease, bone mineral density loss, cardiovascular disease, and metabolic complications. Tenofovir disoproxil fumarate, long a backbone of HIV therapy, has been associated with renal tubular toxicity and bone loss. And while tenofovir alafenamide (Vemlidy; Gilead Sciences) offers an improved safety profile over TDF, INSTIs and tenofovir-containing agents are not universally appropriate across all patients—whether due to INSTI resistance history, pharmacokinetic concerns in older adults, or drug interaction profiles across polypharmacy regimens.3-5
Doravirine/islatravir provides an option that eliminates both tenofovir and integrase inhibitors from the regimen entirely while maintaining virologic efficacy. As Amy Colson, MD, MPH, director of research at Community Resource Initiative, noted in Merck’s announcement: “[Doravirine/islatravir] is the first non-INSTI, tenofovir-free, 2-drug regimen to demonstrate non-inferior efficacy to standard oral antiretroviral regimens, including [BIC/FTC/TAF].” This makes [doravirine/islatravir] a potential alternative for people with virologically suppressed HIV who may need to switch their treatment.”1
Safety Profile and Key Counseling Points for Pharmacists
Pharmacists dispensing doravirine/islatravir should be familiar with several critical counseling points. The drug carries a serious skin reaction warning, including a risk of Stevens-Johnson syndrome and toxic epidermal necrolysis based on postmarketing experience with doravirine-containing regimens, as well as a case of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) in the clinical trial. A single case of severe immune thrombocytopenia was reported in the trials, resolving upon discontinuation. Patients should be counseled to report any progressive or painful rash with mucosal involvement immediately.1
Importantly, patients with hepatitis B virus (HBV) co-infection require specific attention: doravirine/islatravir has no activity against HBV, and patients switching from an ART regimen with HBV activity must be closely monitored for hepatic flares and may require specific anti-HBV therapy.1
For pharmacists, the arrival of doravirine/islatravir introduces both new counseling responsibilities and meaningful new clinical utility—particularly for patients with aging-related comorbidities, prior INSTI exposure, renal concerns, or complex polypharmacy profiles where a tenofovir- and integrase inhibitor-free option may be clinically advantageous.
