Merck Presents New Phase 3 Data for Investigational Two-Drug HIV Regimen Doravirine/Islatravir

Merck Presents New Phase 3 Data for Investigational Two-Drug HIV Regimen Doravirine/Islatravir

By, Admin 16 October 2025

Merck (known as MSD outside the U.S. and Canada) presented additional results from two Phase 3 clinical trials evaluating its investigational, once-daily, oral, two-drug regimen doravirine/islatravir (DOR/ISL 100mg/0.25mg) in adults with HIV-1 infection who were virologically suppressed on standard antiretroviral therapy.

The new data, presented at the 20th European AIDS Conference (EACS) in Paris, build on earlier findings shared at CROI 2025, showing that DOR/ISL maintained viral suppression and demonstrated non-inferiority to three-drug regimens such as bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and baseline ART. Importantly, no treatment-emergent resistance to doravirine or islatravir was observed.

Minimal Impact on Weight, Lipids, and Insulin Resistance

Across both studies (MK-8591A-052 and MK-8591A-051), participants who switched to DOR/ISL experienced minimal changes in body weight, body composition, and fasting lipids compared with those who remained on their existing regimen.

  • In the MK-8591A-052 study, the mean weight change at Week 48 was -0.03 kg for DOR/ISL versus +0.28 kg for BIC/FTC/TAF.
  • Mean changes in lean body mass, trunk fat, BMI, and waist-to-hip ratio were small and comparable across both groups.
  • No clinically meaningful differences were observed in fasting lipids or insulin resistance (HOMA-IR).
  • Initiation of lipid-lowering therapy was low and similar across treatment arms (~5%).

"Weight and body composition are often central concerns for people living with HIV. These findings are important because they show minimal and similar changes when switching to DOR/ISL.”

  • Dr. Chloe Orkin, Dean for Healthcare Transformation, Queen Mary University of London.

Dr. Eliav Barr, Chief Medical Officer, Merck Research Laboratories, added:
"Comorbidities like cardiovascular disease and obesity complicate HIV care. We’re encouraged that switching to DOR/ISL showed minimal effects on weight and lipids while maintaining viral suppression."

Safety Profile and Efficacy Remain Consistent

In both trials, efficacy and safety outcomes were consistent across groups:

  • At Week 48, the percentage of participants with HIV-1 RNA <50 copies/mL was similar between DOR/ISL and comparator groups.
  • Adverse events (AEs) and discontinuations due to AEs were low and balanced.
  • No clinically significant changes in CD4 counts or lymphocyte levels were observed.
  • No cases of hepatitis B reactivation were reported.

The most common AEs (>6%) were arthralgia, fatigue, nasopharyngitis, and COVID-19.

Regulatory Progress

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

About the DOR/ISL Program

Doravirine/islatravir combines:

  • Doravirine (DOR) – a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI).
  • Islatravir (ISL) – a nucleoside reverse transcriptase translocation inhibitor (NRTTI) that blocks HIV replication through multiple mechanisms.

The regimen is being evaluated in multiple Phase 3 studies, including:

  • MK-8591A-053 (treatment-naïve patients)
  • MK-8591A-054 (open-label continuation study)

Merck is also developing long-acting and once-weekly regimens combining islatravir with lenacapavir (Gilead) and ulonivirine (Merck), as well as MK-8527, an investigational once-monthly oral NRTTI for HIV pre-exposure prophylaxis (PrEP).

Merck’s 35-Year Commitment to HIV Innovation

For over three decades, Merck has advanced HIV treatment and prevention through scientific breakthroughs across multiple drug classes. The company continues to focus on transformational therapies, strategic collaborations, and global access initiatives aimed at ending the HIV epidemic

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