Merck HIV combo DOR/ISL matches standard in Phase 3

First non-INSTI two-drug HIV regimen shows non-inferior efficacy and 96-week suppression vs BIC/FTC/TAF, backing an FDA filing due by April 28, 2026.

Feb. 25, 2026 at 5:37pm

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Merck announced late-breaking data from three Phase 3 trials evaluating the investigational, once-daily, oral, two-drug regimen of doravirine/islatravir (DOR/ISL) in adults with HIV-1. The findings showed that DOR/ISL demonstrated non-inferiority to BIC/FTC/TAF in treatment-naive adults at Week 48 and maintained high rates of viral suppression at Week 96 in virologically suppressed adults who switched from other oral antiretroviral therapies, including BIC/FTC/TAF. The safety profile was similar between both treatment groups.

Why it matters

These new Phase 3 results are meaningful, showing that an investigational two-drug regimen without an INSTI demonstrated non-inferior efficacy and a comparable safety profile versus BIC/FTC/TAF in previously untreated adults with HIV-1, including those with advanced disease. Over time, people may need to adjust their HIV treatment regimens because of comorbidities, concerns about toxicities, tolerability challenges, or a desire for regimens with fewer medications. These 96-week data are encouraging, showing a non-INSTI option like investigational DOR/ISL could offer an important alternative.

The details

The Phase 3 MK-8591A-053 trial evaluating DOR/ISL versus BIC/FTC/TAF in treatment-naive adults met its primary efficacy endpoint, demonstrating non-inferiority for DOR/ISL compared to BIC/FTC/TAF at Week 48. The safety profile was similar between both treatment groups. New 96-week data from the Phase 3 MK-8591A-052 and MK-8591A-051 trials evaluating DOR/ISL versus BIC/FTC/TAF or baseline antiretroviral therapy in virologically suppressed adults also showed DOR/ISL maintained high rates of viral suppression and had a similar safety profile.

  • On February 25, 2026, Merck announced the presentation of results from three pivotal Phase 3 trials evaluating DOR/ISL at the 33rd Conference on Retroviruses and Opportunistic Infections (CROI) in Denver.
  • The U.S. FDA has set a target action date of April 28, 2026 for the DOR/ISL New Drug Application under the Prescription Drug User Fee Act (PDUFA).

The players

Merck

A pharmaceutical company that is developing the investigational, once-daily, oral, two-drug regimen of doravirine/islatravir (DOR/ISL) for the treatment of adults with HIV-1.

Jürgen K. Rockstroh

A professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn.

Amy Colson

The director of research at Community Resource Initiative in Cambridge, Massachusetts.

bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)

An approved antiretroviral regimen used as a comparator in the Phase 3 trials of DOR/ISL.

doravirine (DOR)

An antiretroviral medication that is a component of the investigational DOR/ISL regimen.

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What they’re saying

“These new Phase 3 results are meaningful, showing that an investigational two-drug regimen without an INSTI demonstrated non-inferior efficacy and a comparable safety profile versus BIC/FTC/TAF in previously untreated adults with HIV-1, including those with advanced disease.”

— Jürgen K. Rockstroh, Professor of medicine, head of the HIV Outpatient Clinic at the University of Bonn (Merck)

“As people living with HIV age, managing other health conditions becomes a reality for many, making it especially important to have treatment options that can help meet each person's unique health needs.”

— Amy Colson, Director of research at Community Resource Initiative (Merck)

What’s next

The U.S. FDA has set a target action date of April 28, 2026 for the DOR/ISL New Drug Application under the Prescription Drug User Fee Act (PDUFA).

The takeaway

These Phase 3 results for the investigational DOR/ISL regimen demonstrate the potential for a new non-INSTI two-drug HIV treatment option that could provide an important alternative for people living with HIV, especially as they age and need to manage other health conditions.