Once-Daily Switch Pill for Adults with Suppressed HIV

Idvynso (doravirine 100 mg + islatravir 0.25 mg; pronounced ihd-VIHN-soh) is a once-daily, two-drug, tenofovir-free complete regimen. Doravirine is an NNRTI. Islatravir is a nucleoside reverse-transcriptase translocation inhibitor (an NRTI/NRTTI). It is not an integrase inhibitor. It is not Biktarvy, Dovato, or Juluca. It is not labelled to start treatment in someone who has never taken ART, and it is not labelled for people whose current regimen is failing.

The FDA labelled it on 20 April 2026. Health Canada issued a full Notice of Compliance on 3 June 2026 (DIN 02568748). Japan’s MHLW approved イドビンソ配合錠 on 6 March 2026. Europe’s medicines committee is evaluating an application (EMEA/H/C/006642) — that is not a European Commission licence.

This is a switch for people already undetectable. It is not a cure.

Where this is taking place

Pivotal 48-week switch readouts are done. Both labelled trials remain ACTIVE_NOT_RECRUITING on ClinicalTrials.gov because follow-up runs into 2028. That is not a new enrolment slot in a labelled market. Access in the United States is a commercial prescription. Access in Canada is a labelled DIN — ask the HIV clinic whether a bottle is actually on a Canadian shelf yet.

Trial 051 / MK-8591A-051 (NCT05631093) — Phase 3, open-label, switch from any stable oral 2- or 3-drug ART to Idvynso vs staying on baseline ART. Actual n=553. Status ACTIVE_NOT_RECRUITING (CT.gov verified Nov 2025). Primary completion 10 Oct 2024. Estimated completion 11 Jul 2028. Sponsor: Merck Sharp & Dohme LLC. 53 locations / 8 countries. Canadian sites on CT.gov (no PI named, no site-level recruiting flag): Hamilton Health Sciences – Urgent Care Centre – SIS Clinic, Hamilton ON L8S 1A4; Maple Leaf Research, Toronto ON M5G 1K2; Toronto General Hospital, Toronto ON M5G 2M1; Clinique de médecine Urbaine du Quartier Latin, Montreal QC H2L 4E9; Clinique Medicale l’Actuel – Clinical Research, Montreal QC H2L 4P9. These addresses are historical trial sites, not a walk-in clinic directory.

Trial 052 / MK-8591A-052 (NCT05630755) — Phase 3, double-blind, switch from bictegravir/emtricitabine/tenofovir alafenamide (Biktarvy) to Idvynso vs staying on BIC/FTC/TAF. Actual n=514. Status ACTIVE_NOT_RECRUITING. Primary completion 25 Oct 2024. Estimated completion 4 Aug 2028. Countries with sites: United States, United Kingdom, Australia, Chile, Israel, Japan. No Canadian sites on CT.gov.

NCT05705349 (MK-8591A-053) — Phase 3 treatment-naïve. ACTIVE_NOT_RECRUITING. Not the labelled indication in the US, Canada, or Japan. Canadian sites exist on paper (Hamilton, Toronto General, l’Actuel, MUHC, Regina). Do not treat those as a commercial naïve door.

NCT05766501 (MK-8591A-054) — people who already received the older 0.75 mg islatravir tablet. Not a new-patient path.

CT.gov records for 051 and 052 list no expanded access.

Commercial supply (labelled switch): United States; Canada (authorised; first sale not retrieved); Japan (in-country after MHLW). European Union: wait for CHMP and a Commission decision. United Kingdom / Australia / Switzerland / China: licence not found on documents checked.

Approval matrix

Access by country

• United States: HIV clinician. FDA-labelled 20 Apr 2026 for adults already suppressed who are switching, with no virologic failure and no known doravirine resistance. One pink oval tablet (debossed 772) once a day, with or without food. Swallow as a complete regimen — do not add other HIV meds except the labelled extra doravirine dose with rifabutin. DailyMed marketing start 23 Apr 2026. Merck’s “after May 11” line is company. USPI does not mandate a REMS or specialty pharmacy; retail vs specialty is unknown from the label. Merck US adverse-event line on the USPI: 1-877-888-4231. No copay dollars here. Prior authorization still applies. Not for treatment-naïve people. Not for people who are failing.
• Canada (zoom, not a different Access Level): Authorised with a full NOC (not conditions) and a DIN (02568748; 3 Jun 2026). Adult switch, RNA <50, stable regimen, no treatment failure, no known doravirine resistance. Ask the HIV specialist for a prescription and whether a Canadian bottle is actually available — DHPP still reads Approved, and a first-sale date was not retrieved. Authorized ≠ funded. CDA-AMC and pCPA not found. Provincial / territorial / NIHB / RAMQ listing status is unknown. SAP is the wrong door for a labelled product. Merck Canada (PM): 1-800-567-2594 / www.merck.ca — medical information, not a copay program. Do not mail-order a US bottle as the plan. Treatment-naïve patients are not on the Canadian label.
• Japan: In-country commercial after MHLW 6 Mar 2026. 効能 is HIV-1 infection; the 効能注意 restricts to already-treated, suppressed adults without DOR or ISL resistance-associated mutations. NHI listing as an official gazette is unknown here. Not a Canadian or US travel path, and not a naïve start.
• European Union: Application under evaluation (EMEA/H/C/006642) since 21 May 2026. No CHMP opinion found. No Commission licence. Do not import on your own. Named-patient import is a specialist/legal plan, not a DIY order.
• United Kingdom: MHRA authorisation not found. NICE GID-TA11735 was selected 15 Jun 2026 (Board 13 May 2026 reversed the 2025 non-selection), merged with GID-TA11736 on 24 Jul 2026, status Awaiting development. Not a yes. Not an MHRA MA. Ask the HIV clinic; do not assume NHS routine funding.
• Australia / Switzerland / China: Authorisation not found on documents checked. Specialist + local special-access / trial if those programs apply. There is no retrieved compassionate-use ID for this product.

If your regulator has not authorised it: do not import on your own. Travelling to a labelled market (US, Canada, Japan) is only a plan with both specialists.

Who is eligible (from the labels — they are not the same)

This is a switch conversation. If the virus is detectable, or ART has never been started, this tablet is not the US or Canadian labelled next step.

United States (USPI):

• Adult (18+). Safety and effectiveness not established under 18.
• HIV-1 RNA less than 50 copies/mL on a stable antiretroviral regimen.
• No history of virologic treatment failure.
• No known substitutions associated with resistance to doravirine.
• Take one 100/0.25 mg tablet once daily with or without food, alone (complete regimen).
• Not recommended if eGFR <30 mL/min/1.73 m² or Child-Pugh C.
• Active HBV was excluded from the trials; Idvynso has no HBV activity — people with HBV who drop a tenofovir- or lamivudine-containing regimen need an HBV plan.

Canada (Product Monograph):

• Adult. Not established under 18.
• Replace current ART if virologically suppressed (HIV-1 RNA <50), stable regimen, no history of treatment failure, no known substitutions associated with resistance to doravirine.
• Same dose. Therapy should be started by a clinician experienced in HIV-1.
• Hypersensitivity to the drug or any ingredient is a contraindication (lactose monohydrate in the tablet).
• Same renal/hepatic limits as the USPI.
• HBV: no activity; monitor and consider specific anti-HBV therapy if switching off an HBV-active backbone or if HBV is newly diagnosed.

Japan (PMDA table + 効能注意 as quoted by MSD Japan / 添付文書 reprints):

• 効能: HIV-1 infection.
• 注意: already-treated adults, no virologic failure, suppressed ≥3 months (RNA <50), no RAMs to doravirine or islatravir, switch judged appropriate. That “or islatravir” clause is not in the US or Canadian indication sentence.

Not labelled in the US or Canada:

• Treatment-naïve / first ART (NCT05705349 is a different conversation).
• Current virologic failure.
• Children.
• Adding it on top of 3TC, FTC, or another complete HIV regimen.
• HIV-2.

What the pivotal studies showed (label vs journal)

Use the label of the country that will prescribe.

Both trials enrolled adults suppressed ≥3 months, with no history of treatment failure. People with active HBV (HBsAg or HBV DNA positive) were excluded.

FDA / USPI Week 48 (snapshot; HIV-1 RNA ≥50 copies/mL was the primary endpoint; non-inferiority margin 4%):

Trial 051: mean age 50 (18–83); 60% male; 45% Black/African American; 39% White; mean CD4 748 cells/mm³; 64% INSTI-based at entry. Trial 052: mean age 48 (19–77); 79% male; 61% White; 31% Black/African American; mean CD4 717.

CD4 change at Week 48 (USPI): Trial 051 +5 vs +18 cells/mm³; Trial 052 +30 vs +28.

Health Canada PM reports the same trials with slightly more decimal places (1.4% vs 4.9% in 051; 1.5% vs 0.6% in 052; 95.6% vs 91.9% and 91.5% vs 94.2% suppressed). Those decimals are the same two trials, not a second study.

This is non-inferior maintenance of suppression, not a survival trial.

Lancet (journal, not the label): Orkin et al., 2026;407:599-610 (051). Colson et al., 2026;407:611-621 (052). Use the label for a script.

Resistance on the USPI: some Week-48 viremia in people who should not have been enrolled (prior failure and/or doravirine RAMs at baseline). That is why the indication requires no prior virologic failure and no known doravirine resistance.

How it is taken (labelled)

One tablet (100 mg doravirine / 0.25 mg islatravir) by mouth once daily, with or without food. Pink, oval, film-coated, debossed 772. Keep it in the original bottle with the desiccant; do not move tablets into a weekly pillbox.

It is a complete regimen. Do not combine it with other HIV treatment medicines, except:

• Rifabutin: keep the daily Idvynso tablet and take one Pifeltro (doravirine) 100 mg tablet about 12 hours later, for as long as rifabutin continues.

Missed dose:

• US Patient Information: take as soon as remembered; if it is almost time for the next dose, skip; do not take two doses at once.
• Canada / Japan (PM and 用法注意): if within 12 hours of the usual time, take it; if more than 12 hours, skip and resume the next day. Do not double.

Do not take with:

• Strong CYP3A inducers (examples on the Canadian PM: carbamazepine, oxcarbazepine, phenobarbital, phenytoin, enzalutamide, rifampin, rifapentine, mitotane, St John’s wort). Stop those at least 4 weeks before starting (USPI).
• Lamivudine or emtricitabine (they drop intracellular islatravir-triphosphate).
• Other moderate CYP3A inducers besides the labelled rifabutin workaround — not recommended.
• Nucleoside antimetabolites (cladribine, clofarabine, cytarabine, fludarabine, gemcitabine) — not recommended.
• Pentostatin (ADA inhibitor) — not recommended.

No dose adjustment for age ≥65, mild/moderate hepatic impairment, or eGFR ≥30. Not recommended if eGFR <30 or Child-Pugh C. Not studied on dialysis.

Safety (from the USPI; Canadian PM is aligned on the same topics unless noted)

There is no boxed warning. IRIS is not a labelled warning on the USPI or the Canadian PM.

USPI Warnings and Precautions:

• Severe skin reactions — SJS/TEN (postmarketing with doravirine regimens) and DRESS (one Grade 4 case in an ongoing trial about ten weeks after starting Idvynso). Stop Idvynso immediately and get care for a painful rash with mucosal involvement, a progressive severe rash, or a rash with fever, eosinophilia, swollen nodes, or organ involvement.
• Drug interactions — loss of effect or extra toxicity (see contraindications above).

HBV (USPI 8.8 / Canadian PM 7.1.5, not a 5.x warning): Idvynso does not treat hepatitis B. If you switch off a regimen that was covering HBV, or if HBV is newly found, you need monitoring and a specific HBV medicine.

Lymphocytes / CD4 (pharmacodynamics and labs, not a 5.x warning at this dose): higher daily islatravir doses (0.75 mg and above — three times the labelled dose) caused reversible drops in total lymphocytes and CD4 that led to discontinuations in earlier trials. At 0.25 mg, both labels say there was no clinically meaningful lymphocyte/CD4 effect in the Idvynso trials. Do not confuse the old 0.75 mg programme with this tablet.

Most common adverse reactions (≥2% in any Idvynso arm, all grades, Week 48): diarrhea, dizziness, fatigue, abdominal distension, headache, weight increased. Most events were Grade 1–2. Discontinuations for adverse events: 0.5% vs 2% (Trial 051) and 3% vs 2% (Trial 052).

Uncommon but serious on the labels: one case of severe immune thrombocytopenia (platelets 2 × 10⁹/L) 32 days after starting in Trial 052, which resolved after stopping plus steroids and IVIG; three people in the broader DOR+ISL programme with ALT/AST >10× ULN attributed to study drug (two on Idvynso, asymptomatic). Postmarketing with doravirine: hepatitis, raised liver enzymes, SJS/TEN.

Canada-only contraindication: hypersensitivity, including to tablet ingredients (lactose).

Pregnancy: human data insufficient. Antiretroviral Pregnancy Registry: 1-800-258-4263. Animal data did not show developmental harm at high multiples of human exposure. Canada: do not use in pregnancy unless potential benefit outweighs risk; do not breastfeed while taking Idvynso. US: discuss HIV transmission, resistance, and infant side-effect risks of breastfeeding.

Geriatrics: 81 people (11%) in the two trials were ≥65, including 10 ≥75; no overall difference seen.

Research team (Who)

Names below appear on NCT, the USPI/PM, the PMDA table, or the Lancet papers.

• Merck Sharp & Dohme LLC — US NDA holder; trial sponsor (NCT05631093, NCT05630755, NCT05705349). Rahway, NJ on the USPI.
• Merck Canada Inc. — Canadian MAH (RDS; PM; DIN 02568748). Kirkland, QC.
• MSD株式会社 — Japan MAH (PMDA table 6 Mar 2026).
• Medical Director, Merck Sharp & Dohme LLC — CT.gov overall official / study director on 051, 052, and 053. No named site principal investigator on those records.
• Chloe Orkin et al. — Lancet first-author paper for Trial 051 (NCT05631093).
• Amy E. Colson et al. — Lancet first-author paper for Trial 052 (NCT05630755).
• Yamasa Shoyu Co., Ltd. — named in MSD Japan’s 6 Mar 2026 announcement as the islatravir license source. That is company, not the FDA label.

No Canadian principal investigator is named on NCT05631093. Clinic phone numbers are not on CT.gov.

How to talk to a doctor

Bring the NCT numbers and the label of the country you are in.

1. “I am an adult, already undetectable on a stable regimen. In this country, is Idvynso (doravirine/islatravir 100/0.25 mg once daily) a labelled switch for me?”
2. “Have I ever had virologic failure? Do I have known doravirine resistance? (Japan also asks about islatravir RAMs.)”
3. “Does my current pill contain 3TC or FTC that must come off, and do I have hepatitis B that those drugs were covering?”
4. “I take rifampin / carbamazepine / St John’s wort / rifabutin / a cancer nucleoside — is this combination contraindicated or does it need the extra Pifeltro dose?”
5. “What is the rash stop-rule (SJS/TEN/DRESS)?”
6. “I am not starting ART for the first time, and I am not failing — if I were, this tablet is not labelled here. Is NCT05705349 even relevant, and is enrolment closed?”
7. Canada: “This is a full NOC, DIN 02568748. SAP is the wrong door. What is actually funded in this province, and is a Canadian bottle in the pharmacy yet? I do not have a listing answer.”
8. US: “Is prior authorization the only remaining step?”
9. EU / UK / Australia / Switzerland / China: “No licence found (EU is under evaluation). Is a later Commission/MHRA decision, a trial, or a planned visit to a labelled country the door?”
10. Pregnancy registry 1-800-258-4263 if that applies.

Canada zoom: authorised, not funded-by-default

Health Canada has already authorised Idvynso with a full NOC, and it has a DIN. That is not a compassionate-access story and it is not NOC/c. The remaining Canadian questions are who pays (status unknown) and whether first sale has happened (DHPP still Approved on 2026-09-02). Do not call the clinic asking for SAP. Do not assume a provincial formulary has listed it because a DIN exists. This tablet is not labelled for someone who is treatment-naïve or failing.

Bottom line

Idvynso is a labelled once-daily two-drug, tenofovir-free complete regimen for adults already suppressed on stable ART, with no prior virologic failure and no known doravirine resistance, in the United States (20 Apr 2026) and Canada (NOC 3 Jun 2026). Japan approved イドビンソ on 6 Mar 2026 as a switch in already-treated, suppressed adults (the Japanese 効能注意 also bars known islatravir RAMs). Europe has an application under evaluation, not a Commission pack. The UK, Australia, Switzerland, and China have no retrieved licence. NICE GID-TA11735 is Selected (15 Jun 2026; merged with GID-TA11736) and Awaiting development — not a yes. Canada’s NOC is authorised, not a funding decision. SAP is the wrong door. The Phase 3 switch trials are closed to enrolment. This tablet is not for people starting HIV treatment and not for people whose current regimen is failing. Authorized is not funded.

Primary sources

1. FDA Novel Drug Approvals 2026 (Idvynso, No. 12, 4/20/2026) — https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2026
2. Drugs@FDA NDA 216964 — https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=216964
3. USPI PDF, NDA 216964 — https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/216964Orig1s000lbl.pdf
4. DailyMed IDVYNSO (setid 11aaeb53-9848-433c-be7f-db8a5bc0b26f) — https://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=11aaeb53-9848-433c-be7f-db8a5bc0b26f
5. Merck USPI circular (same label) — https://www.merck.com/product/usa/pi_circulars/i/idvynso/idvynso_pi.pdf
6. Health Canada Regulatory Decision Summary, control 298314, NOC 2026-06-03, DIN 02568748 — https://dhpp.hpfb-dgpsa.ca/review-documents/resource/RDS1782826448973
7. Health Canada DHPP product page (Approved; DIN 02568748) — https://dhpp.hpfb-dgpsa.ca/dhpp/resource/107103
8. Canadian Product Monograph (HRES 00085075; Date of Authorization 2026-06-03) — https://pdf.hres.ca/dpd_pm/00085075.PDF
9. PMDA 承認品目一覧（新医薬品：2025年4月～2026年3月）No. 75, 2026.3.6 — https://www.pmda.go.jp/files/000277965.pdf
10. MSD Japan approval announcement, 6 Mar 2026 (company; quotes 効能注意) — https://www.msd.co.jp/news/product-news-20260306/
11. EMA applications for new human medicines under evaluation, August 2026 (EMA/180125/2026 corr.; data extracted 4 Aug 2026) — https://www.ema.europa.eu/en/medicines/medicines-human-use-under-evaluation
12. EMA PIP decision P/0268/2024 (doravirine/islatravir; EMEA-002707-PIP01-19-M02) — https://www.ema.europa.eu/en/documents/pip-decision/p-0268-2024-ema-decision-17-july-2024-acceptance-modification-agreed-paediatric-investigation-plan-doravirine-islatravir-emea-002707-pip01-19-m02_en.pdf
13. NICE GID-TA11735 / TSID12171 (Selected 15 Jun 2026; Awaiting development; not a yes) — https://www.nice.org.uk/guidance/indevelopment/gid-ta11735
14. ClinicalTrials.gov NCT05631093 (MK-8591A-051) — https://clinicaltrials.gov/study/NCT05631093
15. ClinicalTrials.gov NCT05630755 (MK-8591A-052) — https://clinicaltrials.gov/study/NCT05630755
16. ClinicalTrials.gov NCT05705349 (MK-8591A-053, treatment-naïve; not labelled) — https://clinicaltrials.gov/study/NCT05705349
17. ClinicalTrials.gov NCT05766501 (MK-8591A-054) — https://clinicaltrials.gov/study/NCT05766501
18. Orkin C, et al. Switch to fixed-dose doravirine (100 mg) and islatravir (0.25 mg) once daily in virologically suppressed adults with HIV-1 on oral antiretroviral therapy. Lancet. 2026;407(10528):599-610. DOI 10.1016/S0140-6736(25)01945-2 (journal; not the label)
19. Colson AE, et al. Switch to fixed-dose doravirine (100 mg) and islatravir (0.25 mg) once daily in virologically suppressed adults with HIV-1 on bictegravir, emtricitabine, and tenofovir alafenamide. Lancet. 2026;407(10528):611-621. DOI 10.1016/S0140-6736(25)01948-8 (journal; not the label)
20. Merck company FDA announcement, 21 Apr 2026 (company; not the legal act) — https://www.merck.com/news/fda-approves-mercks-once-daily-idvynso-doravirine-islatravir/

Who (from sources)