Islatravir
What it isInvestigational nucleoside reverse transcriptase translocation inhibitor (NRTTI, MK-8591) with an exceptionally long intracellular half-life.
Why this oneIts potency and half-life enable ultra-low-dose, long-acting HIV regimens such as once-weekly and once-daily oral combinations.
What limits itHigher doses caused dose-dependent declines in CD4 and total lymphocyte counts, prompting lower dosing, and it remains investigational and not FDA-approved.
FDA-approved for
- HIV-1 infection (with doravirine) (2026)
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| HIV-1 infection (virologically suppressed, switch regimen per trials) | adults | 1 tablet (doravirine 100 mg / islatravir 0.25 mg) QD | 1 tablet QD | 1 tablet QD |
Renal eGFR >=30 mL/min/1.73m2: no adjustment. eGFR <30: not recommended. Dialysis: not studied
Hepatic Mild/moderate (Child-Pugh A/B): no adjustment. Severe (Child-Pugh C): not recommended (not studied)
Instructions
- Take with or without food
- With rifabutin: take IDVYNSO QD, then add one doravirine (PIFELTRO) 100 mg tablet ~12 h after the IDVYNSO dose, for the duration of rifabutin
Contraindications
- Strong CYP3A inducers — drop doravirine levels, loss of efficacy
- Lamivudine (3TC) or emtricitabine (FTC) — dCK substrates that lower islatravir-triphosphate, loss of efficacy
Cautions
- Severe skin reactions (SJS/TEN with doravirine regimens; DRESS in an IDVYNSO trial) — discontinue immediately at signs of severe rash with mucosal/constitutional/organ involvement
- Drug interactions may cause loss of virologic response or adverse reactions — review co-medications
- No HBV activity: monitor HBV-co-infected patients and consider specific anti-HBV therapy
Adverse reactions
- Diarrhea, dizziness, fatigue, abdominal distension, headache, weight increase (>=2%)
- One case of severe immune thrombocytopenia; one Grade 4 DRESS (both resolved on discontinuation)
- Asymptomatic ALT/AST elevations
- Postmarketing (doravirine regimens): hepatitis, hepatic enzyme increase, SJS/TEN
Pregnancy Insufficient human data (animal studies: no developmental effects at >=8x/500x RHD exposures); pregnancy exposure registry available (APR 1-800-258-4263)
Lactation Unknown if present in human milk; breastfeeding risks: HIV-1 transmission, viral resistance in infected infants, adverse reactions in infant
NO BOXED WARNINGS
Principal riskNo FDA boxed warning.
Classes and tags
Clinical profile
Mechanism of action: Islatravir ballicule
