Idvynso (doravirine and islatravir): FDA approval, pivotal trial and safety
Approved
Type
New molecular entity · Oral
FDA-approved use
To treat HIV-1 infection (as a complete regimen) in adults to replace the current antiretroviral regimen in those who are virologically-suppressed on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirineWording from FDA's list of novel approvals.
FDA review
Standard review
Company
Merck
Application
NDA 216964
Specialty
Infectious Disease
At a glance
Idvynso is a once-daily, two-drug tablet of doravirine and islatravir. It is approved for virologically suppressed adults with HIV-1 who want to replace a stable regimen, with no history of treatment failure and no known doravirine resistance. In the open-label switch trial, HIV-1 RNA of 50 copies/mL or higher at Week 48 occurred in 1.4% with the switch versus 4.9% with baseline therapy (difference -3.6%, 95% CI -7.8 to -0.8), meeting non-inferiority. Severe skin reactions are the main warning.
What it is and how it works
Doravirine is a non-nucleoside reverse transcriptase inhibitor. Islatravir is a nucleoside analog reverse transcriptase inhibitor. Together they form a complete two-drug regimen. The authors describe it as the first two-drug regimen for HIV-1 that is not built on an integrase strand-transfer inhibitor (INSTI).
Phase 3, randomized, open-label, active-controlled, non-inferiority trial at 53 sites in eight countries. Randomization was 2:1 and stratified by anchor drug class. Follow-up was 48 weeks.
Patients
551 treated adults (366 switch, 185 continuing). All were suppressed (HIV-1 RNA below 50 copies/mL) on an oral regimen for at least 3 months, with no treatment failure, known doravirine resistance, or active hepatitis B. Median age was 51 years, 60% were assigned male at birth, and 45% were Black or African American.
Compared with
Continued baseline oral antiretroviral therapy
Primary endpoint
Percentage with HIV-1 RNA of 50 copies/mL or higher at Week 48 (FDA snapshot). Non-inferiority required the upper bound of the adjusted 95% CI to be below 4%.
Result
5 of 366 (1.4%) with Idvynso versus 9 of 185 (4.9%) with baseline therapy. Difference -3.6% (adjusted 95% CI -7.8 to -0.8). Non-inferiority was met.
Other results
Not detailed in the sources beyond safety outcomes.
Safety in the trial
Treatment-related adverse events occurred in 12.0% vs 4.9%. Any adverse event occurred in 79.5% vs 83.8%, and serious adverse events in 6.3% vs 4.9%. Discontinuation for adverse events occurred in 0.5% vs 2.2%. One death occurred, in the baseline therapy group, and was not treatment-related. No one stopped for protocol-defined declines in CD4 or lymphocyte counts.
How does Idvynso (doravirine and islatravir) compare with the alternatives (Bictegravir/emtricitabine/tenofovir alafenamide, Dolutegravir/lamivudine, Dolutegravir/rilpivirine) for HIV-1 infection (as a complete regimen) in adults to replace the current antiretroviral regimen in those who are virologically-suppressed on a stable antiretroviral regimen with no history of virologic treatment failure…? Summarize head-to-head and indirect evidence, efficacy, safety and where each fits, with citations.
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Safety signals
There is no boxed warning. Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS, are a warning. DRESS was reported in a clinical trial, and the drug should be stopped immediately if a severe rash develops. Drug interactions can reduce efficacy and risk resistance, or raise exposure to a component, so review concomitant medications. The most common adverse reactions (2% or more) were diarrhea, dizziness, fatigue, abdominal distension, headache, and weight increase. Most adverse events in treated participants were mild or moderate. People with active hepatitis B infection were excluded from the trials.
What it competes with
Virologically suppressed adults are usually kept on a stable regimen, most often an INSTI-based combination, and switched for tolerability, interactions, or simplification. Both two-drug and three-drug options are used.
Bictegravir/emtricitabine/tenofovir alafenamideSingle-tablet INSTI-based three-drug regimen, and the active comparator in Trial 052.
Dolutegravir/rilpivirineTwo-drug switch regimen for suppressed adults.
Doravirine/lamivudine/tenofovir disoproxil fumarateThree-drug single-tablet regimen that also contains doravirine.
Bottom line for clinicians
Idvynso suits suppressed adults without prior virologic failure or doravirine resistance who need a change, particularly if an INSTI-free option is wanted. Consider drug interactions, the rash and DRESS warning, and the exclusion of active hepatitis B from the trials. Treatment-related adverse events were more frequent than with continued therapy in the open-label trial.
Dosing, contraindications and full warnings are in the prescribing information.
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Last updated October 28, 2026 by 2 Minute Medicine.
For healthcare professionals. A summary of public FDA documents and published trials, not medical advice. Check the full prescribing information before prescribing.
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