TOPLINE:

In patients with HIV‑1 infection and virologic suppression, an investigational once-daily regimen of doravirine plus islatravir was noninferior to standard antiretroviral therapy (ART) in maintaining viral suppression and had a comparable safety profile at 48 weeks.

METHODOLOGY:

• Researchers conducted a phase 3 randomized, noninferiority trial across eight countries to assess the efficacy and safety of switching from stable oral ART to doravirine plus islatravir in patients with HIV-1 infection and virologic suppression.
• A total of 551 patients (median age, 51 years; 40% assigned female sex at birth) were randomly assigned and treated for 48 weeks: 366 switched to a once-daily oral tablet containing 100 mg doravirine plus 0.25 mg islatravir, and 185 continued their baseline ART regimen.
• Viral load was assessed by measuring HIV-1 RNA copy numbers at each prespecified visit through week 48.
• The primary endpoint was the percentage of patients with a viral load of at least 50 copies per mL at week 48; noninferiority was confirmed if the upper bound of the multiplicity-adjusted 95% CI for the treatment difference was less than 4%.
• Secondary endpoints included the percentage of patients with a viral load below 50 copies per mL and the mean change in CD4 count; safety assessments included adverse events and the mean change in total lymphocyte count.

TAKEAWAY:

• At week 48, 1.4% of patients who switched to doravirine plus islatravir had a viral load of 50 copies per mL or higher compared with 4.9% of those who continued the baseline ART regimen (difference, -3.6%; multiplicity-adjusted 95% CI, -7.8 to -0.8), meeting the noninferiority criteria.
• A viral load of less than 50 copies per mL was maintained at week 48 in 95.6% of patients in the doravirine plus islatravir group vs 91.9% in the baseline ART group (difference, 3.8%; 95% CI, -0.3 to 8.9).
• No clinically meaningful between-group differences were observed for the mean changes from baseline in CD4 cell count or total lymphocyte count at week 48.
• The overall safety profile was similar between the groups, with comparable rates of serious adverse events. Treatment-related adverse events were more frequent with doravirine plus islatravir, but discontinuations for these events were uncommon in both groups, and no deaths were attributable to treatment.

IN PRACTICE:

“Doravirine and islatravir could provide a potent alternative for patients unable to use INSTIs [integrase strand-transfer inhibitors] owing to contraindications, intolerance, or drug interactions. The pharmacological simplicity of this regimen makes it attractive for individuals with multimorbidity and polypharmacy,” experts wrote in a commentary accompanying the journal article. 

SOURCE:

The study was led by Chloe Orkin, MD, Queen Mary University of London, London, England. It was published online on February 7, 2026, in The Lancet.

LIMITATIONS:

The open‑label design of the trial could have influenced the reporting of subjective outcomes such as adverse events. The trial had a short duration of only 48 weeks. It also included a highly selected population of patients with virologic suppression and no prior treatment failures or known resistance, limiting generalizability to more complex clinical scenarios.

DISCLOSURES:

This trial was funded by Merck Sharp & Dohme, a subsidiary of Merck & Co. Nine authors were employees of Merck Sharp & Dohme and may have owned stock or held stock options in Merck & Co. Several other authors reported receiving grants, consulting fees, honoraria, or travel support from or serving on advisory boards or data safety monitoring boards for multiple pharmaceutical companies, including Merck Sharp & Dohme.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.