DOR/ISL Maintains Viral Suppression in Phase 3 HIV Trials: Princy Kumar, MD

A 2-drug HIV regimen containing doravirine and islatravir demonstrated strong efficacy and a favorable safety profile in a pair of phase 3 clinical trials, supporting its recent FDA approval. The newly approved single-tablet regimen is a fixed-dose combination of doravirine and islatravir (DOR/ISL; Idvysno; Merck), which is indicated for adults with virologically suppressed HIV-1 who have no history of treatment failure and no known resistance to DOR.

Findings from MK-8591A-052 (Trial 052; NCT05630755) and MK-8591A-051 (Trial 051; NCT05631093) establish the therapy’s potential as a switch option for patients who are already virologically suppressed on standard antiretroviral therapy, according to Princy Kumar, MD, who led one of the clinical trials at Georgetown University Medical Center. She also serves as chief of infectious diseases at MedStar Georgetown University Hospital and professor of medicine and microbiology at Georgetown University.

In an interview with The American Journal of Managed Care^®, Kumar explained that the studies were designed as noninferiority trials because researchers sought to determine whether the 2-drug regimen could perform as well as existing 3-drug regimens in patients who were already stable on treatment.

“We wanted to show that a 2-drug regimen that does not have an integrase inhibitor or tenofovir would be as efficacious and safe as a 3-drug regimen that the patient already is tolerating,” Kumar said.

The enrolled patients were already virologically suppressed, stable on therapy, and tolerating their regimens well, making noninferiority the most clinically relevant approach. Kumar noted that with multiple highly effective HIV therapies currently available, the goal was to determine whether DOR/ISL could provide another reliable option for treatment simplification.

Kumar highlighted that more than 90% of patients maintained completely undetectable viral loads after switching therapies, which she described as particularly reassuring from a clinical perspective. While the FDA focuses on rates of viral loads exceeding 50 copies/mL in evaluating noninferiority, Kumar emphasized that clinicians often prioritize whether patients’ viral loads remain fully undetectable.

Safety and tolerability findings were also notable, particularly regarding metabolic outcomes and weight changes. Kumar characterized the regimen as both “metabolically neutral and weight neutral,” adding that the absence of significant adverse metabolic effects could be important for long-term treatment decisions.

She also pointed to findings from one of the trials comparing DOR/ISL with bictegravir-containing regimens, where the 2-drug therapy showed no meaningful weight gain. In another study comparing the regimen with standard-of-care therapies, weight changes appeared comparable overall, although Kumar noted that discontinuation of efavirenz- or tenofovir-containing regimens may itself contribute to weight increases because both agents can suppress weight.