Merck Reports Positive Phase 3 Results For Once-Daily Oral HIV Regimen Doravirine/Islatravir Presented At CROI In Denver

Merck, known as MSD outside the United States and Canada, announced new results from three pivotal Phase 3 trials evaluating its investigational once-daily oral two-drug regimen, doravirine/islatravir (DOR/ISL), in adults with HIV-1. The data were presented during late-breaking sessions at the 33rd Conference on Retroviruses and Opportunistic Infections (CROI) in Denver.

Dr. Eliav Barr, senior vice president, head of global clinical development, and chief medical officer at Merck Research Laboratories, noted that these findings build on the company’s 40-year commitment to HIV research. He explained that islatravir works through multiple mechanisms, including reverse transcriptase translocation inhibition, and has the potential to support a variety of two-drug daily and weekly treatment options. If approved, DOR/ISL would be the first of these regimens in Merck’s portfolio and could provide a new option for people living with HIV.

One of the key studies, the Phase 3 double-blind trial MK-8591A-053, compared DOR/ISL with bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) in adults with HIV-1 who had not received prior antiretroviral therapy. The trial met its primary endpoint by showing that DOR/ISL was non-inferior to BIC/FTC/TAF in achieving viral suppression (HIV-1 RNA <50 copies/mL) at Week 48—91.8% versus 90.6% respectively. The safety profiles were comparable, with similar rates of drug-related adverse events and discontinuations. These results, published concurrently in The Lancet HIV, add to previously reported Phase 3 data in virologically suppressed adults and will support upcoming regulatory filings.

Dr. Jürgen K. Rockstroh, professor of medicine and head of the HIV Outpatient Clinic at the University of Bonn, highlighted that the findings are important for the HIV community. He pointed out that the study included a diverse global population, including participants with high viral loads and low CD4 counts, and still demonstrated non-inferior efficacy and a consistent safety profile. He noted that these results strengthen the evidence supporting the potential value of DOR/ISL as a treatment option.

Additional 96-week data from the Phase 3 MK-8591A-052 and MK-8591A-051 trials were also shared. These studies evaluated adults with virologically suppressed HIV-1 who switched to DOR/ISL from either BIC/FTC/TAF or their baseline antiretroviral therapy (bART). In both trials, participants who switched maintained high levels of viral suppression through Week 96, with safety results comparable to their previous regimens. 

The 48-week outcomes from these studies were included in the New Drug Application for DOR/ISL in adults who are virologically suppressed and stable on therapy. The U.S. FDA has assigned a target action date of April 28, 2026, under the Prescription Drug User Fee Act. In the United States, doravirine is already approved as a single agent (PIFELTRO) and as part of the single-tablet regimen DELSTRIGO, which combines doravirine, lamivudine, and tenofovir disoproxil fumarate.

Dr. Amy Colson, director of research at the Community Resource Initiative, emphasized that as people with HIV age, they often develop other health conditions that make flexible treatment options increasingly important. She explained that patients may need to adjust their regimens due to comorbidities, tolerability concerns, or a preference for simpler combinations. The 96-week results, she said, suggest that the investigational non-INSTI regimen DOR/ISL could provide a meaningful alternative for many individuals.