Drug Update · Infectious Disease

FDA Approves doravirine/islatravir for Virologically Suppressed HIV‑1: 1% ≥50 copies/mL

August 14, 2026

Approval date

04/20/2026

Indication

Complete two‑drug regimen to replace current ART in virologically‑suppressed adults (HIV‑1 RNA <50 copies/mL) with no history of virologic failure and no known doravirine resistance substitutions [1]

Recommended dose

One tablet once daily containing 100 mg doravirine and 0.25 mg islatravir [1]

Primary endpoint result (Week 48)

HIV‑1 RNA ≥50 copies/mL: 1% in IDVYNSO arms in Trial 051 and Trial 052; Trial 051: 1% vs 5% baseline ART (treatment difference -3.6%; 95% CI -7.8%, -0.8%); Trial 052: 1% vs 1% BIC/FTC/TAF (treatment difference 0.9%; 95% CI -1.9%, 2.9%) [8][1]

Clinical Perspective

Clinicians who manage adults living with HIV (infectious disease specialists, HIV care clinicians, and other prescribers treating virologically suppressed adults) now have an FDA‑approved single‑tablet, two‑drug option to replace a current antiretroviral regimen in patients who meet the label criteria. The Week 48 data from the randomized Trials 051 and 052 showing 1% of IDVYNSO recipients had HIV‑1 RNA ≥50 copies/mL support the indication for switching virologically suppressed adults without prior virologic failure or known doravirine resistance substitutions. How the required postmarketing studies to evaluate resistance substitutions and pediatric populations will influence long‑term safety and use remains to be determined?

Dr. Simran Kohli, MBBS, MD (General Medicine), DM (Infectious Diseases) · Infectious Diseases

The U.S. Food and Drug Administration approved IDVYNSO (doravirine and islatravir) as a complete two‑drug regimen for the treatment of HIV‑1 infection in adults who are virologically suppressed (HIV‑1 RNA less than 50 copies/mL) on a stable antiretroviral regimen with no history of virologic treatment failure and no known substitutions associated with resistance to doravirine. The approval was effective April 20, 2026 and was supported by Week 48 data from two randomized, active‑controlled, non‑inferiority trials (Trial 051 and Trial 052) showing HIV‑1 RNA ≥50 copies/mL occurred in 1% of IDVYNSO recipients in both trials (Trial 051: 1% IDVYNSO vs 5% baseline ART; Trial 052: 1% IDVYNSO vs 1% BIC/FTC/TAF) ^[1]^[2]^[4].

Clinical Context

IDVYNSO is a fixed‑dose, single‑tablet combination of doravirine (a non‑nucleoside reverse transcriptase inhibitor, NNRTI) and islatravir (a nucleoside analog reverse transcriptase inhibitor, NRTI) developed and marketed by Merck (MSD) ^[1]^[3]. The FDA‑approved indication specifies switching adults living with HIV‑1 who are virologically suppressed (HIV‑1 RNA <50 copies/mL) on a stable antiretroviral regimen and who have no history of virologic treatment failure and no known doravirine resistance‑associated substitutions to IDVYNSO as a complete regimen ^[1]^[4]. Merck characterized IDVYNSO as a non‑INSTI, tenofovir‑free, once‑daily two‑drug regimen and reported availability in pharmacies after May 11, 2026 ^[3]. The approved product contains 100 mg doravirine and 0.25 mg islatravir per tablet ^[1]. Clinicians should consult current prescribing information for full dosing guidance.

Key Findings

Trial 051 (open‑label, randomized switch trial) showed HIV‑1 RNA ≥50 copies/mL at Week 48 occurred in 1% of participants switched to IDVYNSO versus 5% of participants who remained on their baseline ART; the treatment difference was -3.6% (95% CI -7.8%, -0.8%) ^[4]^[1].
Trial 052 (double‑blind, randomized switch trial versus bictegravir/emtricitabine/tenofovir alafenamide) showed HIV‑1 RNA ≥50 copies/mL at Week 48 occurred in 1% of participants switched to IDVYNSO and 1% of participants who remained on BIC/FTC/TAF; the treatment difference was 0.9% (95% CI -1.9%, 2.9%) ^[4]^[1].
Across the two Phase 3 trials supporting approval, a total of 708 participants received once‑daily IDVYNSO and the primary endpoint in both trials was the proportion of participants with HIV‑1 RNA ≥50 copies/mL at Week 48 ^[1]^[4].

Safety & Tolerability

Severe skin reactions, including Stevens‑Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) have been reported; discontinue IDVYNSO immediately if signs or symptoms of severe skin reactions develop ^[1].
The most common adverse reactions (incidence ≥2%) reported in Trials 051 and 052 were diarrhea, dizziness, fatigue (including asthenia), abdominal distension, headache, and weight increased ^[1].
Hepatic laboratory abnormalities (Grades 2–4) were observed in Trials 051 and 052 and were generally asymptomatic and resolved without discontinuation; alanine aminotransferase and aspartate aminotransferase worsening from baseline occurred at Grade 2 in up to 2% of participants in some groups ^[1].
Postmarketing reports with doravirine‑containing regimens have included hepatitis and increased hepatic enzymes, and SJS/TEN ^[1].

Study Design

The FDA approval was supported by two randomized, active‑controlled, non‑inferiority Phase 3 trials, Trial 051 and Trial 052, enrolling virologically suppressed adults (HIV‑1 RNA <50 copies/mL) who had been stable on baseline ART for at least 3 months ^[1]^[4]. Trial 051 was an open‑label randomized (2:1) switch study (N randomized = 551; IDVYNSO N=366; baseline ART N=185) and Trial 052 was a double‑blind randomized (2:1) switch study versus BIC/FTC/TAF (N randomized = 513; IDVYNSO N=342; BIC/FTC/TAF N=171). The primary endpoint in both trials was the proportion of participants with HIV‑1 RNA ≥50 copies/mL at Week 48 ^[4]^[1]. The NDA (216964) was approved effective April 20, 2026 ^[2].

FAQ

Q1 What is IDVYNSO (IDVYNSO™) approved for?

IDVYNSO is approved as a complete, two‑drug, single‑tablet regimen (doravirine and islatravir) for the treatment of HIV‑1 infection in adults to replace the current antiretroviral regimen in those who are virologically suppressed (HIV‑1 RNA less than 50 copies/mL) on a stable antiretroviral regimen, provided they have no history of virologic treatment failure and no known substitutions associated with resistance to doravirine. The approval was effective April 20, 2026. Q2 How does IDVYNSO work?

IDVYNSO is a fixed‑dose combination of doravirine, a non‑nucleoside reverse transcriptase inhibitor (NNRTI), and islatravir, a nucleoside analog reverse transcriptase inhibitor (NRTI). The product label describes the two‑drug combination as a regimen for HIV‑1 treatment; detailed mechanism of action and microbiology information are provided in the full prescribing information. Q3 What is the recommended dose of IDVYNSO?

The recommended dosage of IDVYNSO is one tablet taken orally once daily with or without food. Each tablet contains 100 mg doravirine and 0.25 mg islatravir, which is the FDA‑approved dose. Clinicians should consult current prescribing information for full dosing guidance. Q4 What are the most common side effects of IDVYNSO?

The most common adverse reactions (incidence ≥2% across Trials 051 and 052) were diarrhea, dizziness, fatigue (including asthenia), abdominal distension, headache, and weight increased. Severe skin reactions, including Stevens‑Johnson syndrome and toxic epidermal necrolysis, and DRESS have been reported; discontinuation is recommended if severe skin reactions occur. Hepatic enzyme elevations and postmarketing reports of hepatitis have also been observed. Clinicians should consult current prescribing information for full dosing guidance.

FDA Approves doravirine/islatravir for Virologically Suppressed HIV‑1: 1% ≥50 copies/mL

Direct Clinical Takeaway & Evidence Summary

FDA Approves doravirine/islatravir for Virologically Suppressed HIV‑1: 1% ≥50 copies/mL

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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