FDA Approves Doravirine/Islatravir Once-Daily 2-Drug Regimen for Virologically Suppressed HIV-1

The US Food and Drug Administration (FDA) has approved a fixed-dose combination of doravirine 100 mg and islatravir 0.25 mg as a once-daily, single-tablet regimen for adults with HIV-1 infection who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen, with no history of virologic treatment failure and no known resistance to doravirine.¹

The therapy is indicated as a replacement regimen and represents a complete 2-drug option that does not require coadministration with other antiretroviral agents.¹

According to the announcement, the regimen is the first non–integrase strand transfer inhibitor (INSTI), tenofovir-free, once-daily, complete 2-drug regimen to demonstrate noninferior efficacy compared with a 3-drug regimen in a head-to-head phase 3 trial.¹

“Advances in HIV treatment mean more people living with HIV are living longer — a remarkable achievement,” Carl Baloney, Jr., president and chief executive officer of AIDS United, said in a press release. “People aging with HIV face additional health challenges, including managing multiple chronic conditions and medications at the same time. It is essential that management of HIV considers these factors in addition to virologic suppression when choosing an HIV treatment regimen.”¹

Phase 3 Evidence Demonstrates Noninferior Efficacy^2,3

Approval was supported by week 48 data from two randomized, active-controlled, noninferiority trials (Trial 052 [NCT05630755] and Trial 051 [NCT05631093]) in virologically suppressed adults.

Across both trials, 708 participants received the doravirine/islatravir regimen, including 81 (11%) aged ≥65 years and 10 (1%) aged ≥75 years.

Trial 052 (Switch from bictegravir/emtricitabine/tenofovir alafenamide)

• Participants randomized 2:1 to doravirine/islatravir (n=342) or continued comparator (n=171)
• Primary endpoint (HIV-1 RNA ≥50 copies/mL at week 48): 1% vs 1% (difference 0.9%; 95% CI, −1.9% to 2.9%)
• Viral suppression maintained in 92% vs 94%

Trial 051 (Switch from baseline ART)

• Participants randomized 2:1 to doravirine/islatravir (n=366) or baseline ART (n=185)
• Primary endpoint: 1% vs 5% (difference −3.6%; 95% CI, −7.8% to −0.8%)
• Viral suppression maintained in 96% vs 92%

Efficacy outcomes were consistent across subgroups by age, sex, and race.

Safety Profile and Adverse Events¹

The safety profile of doravirine/islatravir was generally comparable to standard antiretroviral regimens across both phase 3 trials. By week 48, adverse events leading to discontinuation occurred in 3% of participants receiving doravirine/islatravir compared with 2% in the comparator group in Trial 052, and in 0.5% versus 2%, respectively, in Trial 051.

The most commonly reported adverse reactions, occurring in at least 2% of participants in any treatment group, included diarrhea, dizziness, fatigue, abdominal distention, headache, and weight increase. Rates were generally low and similar between treatment groups, with diarrhea reported in up to 3% of participants receiving doravirine/islatravir.

Changes in body weight were minimal over 48 weeks. In Trial 052, mean weight change from baseline was −0.03 kg in the doravirine/islatravir group compared with 0.28 kg in the comparator group, while in Trial 051, mean weight increased by 0.94 kg in the doravirine/islatravir group and decreased by 0.15 kg in the baseline antiretroviral therapy group.

Serious adverse events were uncommon but clinically important. Severe skin reactions, including Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with doravirine-containing regimens, and drug reaction with eosinophilia and systemic symptoms was observed with doravirine/islatravir in a clinical trial. The regimen should be discontinued immediately if these reactions are suspected.

A single case of severe immune thrombocytopenia was reported, characterized by abrupt onset of bleeding manifestations and a platelet nadir of 2 × 10⁹/L approximately 32 days after treatment initiation. The event resolved following discontinuation of therapy and treatment with corticosteroids and intravenous immunoglobulin. No consistent pattern of platelet decline was observed across the study population.

Drug Interactions and Clinical Considerations¹

The regimen is contraindicated with:

• Strong cytochrome P450 3A enzyme inducers
• Lamivudine or emtricitabine

Clinicians should review concomitant medications due to potential for reduced efficacy or increased adverse effects.

The regimen does not have activity against hepatitis B virus; patients with coinfection should be monitored and managed accordingly.

“IDVYNSO is the first non-INSTI, tenofovir-free, two-drug regimen to demonstrate non-inferior efficacy to standard oral antiretroviral regimens, including BIKTARVY. This makes IDVYNSO a potential alternative for people with virologically suppressed HIV who may need to switch their treatment,” said Amy Colson, MD.

The therapy is expected to become available in US pharmacies after May 11.

References:

1. Merck. FDA Approves Merck’s Once-Daily IDVYNSO™ (doravirine/islatravir). News release. April 21, 2026. Accessed April 22, 2026. https://www.merck.com/news/fda-approves-mercks-once-daily-idvynso-doravirine-islatravir/
2. Merck. A study to evaluate switching to doravirine/islatravir (MK-8591A) in virologically suppressed participants with HIV-1 infection (MK-8591A-052). ClinicalTrials.gov identifier: NCT05630755. Updated November 18, 2025. Accessed April 22, 2026. https://clinicaltrials.gov/study/NCT05630755
3. Merck. A study to evaluate switching to doravirine/islatravir (MK-8591A) in virologically suppressed participants with HIV-1 infection (MK-8591A-051). ClinicalTrials.gov identifier: NCT05631093. Updated November 21, 2026. Accessed April 22, 2026. https://clinicaltrials.gov/study/NCT05631093