dolutegravir
Brand: Tivicay, Dovato (with lamivudine), Triumeq (with abacavir/lamivudine)
Prototype: raltegravir
Drug Class: antiretroviral
Drug Family: antiretroviral
Subclass: HIV integrase strand transfer inhibitor (INSTI)
Organ Systems: infectious-disease
Mechanism of Action
Inhibits HIV integrase by binding to the active site and blocking the strand transfer step, preventing integration of HIV cDNA into the host chromosome; highly potent with a high genetic barrier to resistance.
HIV integrase
Indications
- HIV-1 infection (treatment-naive and treatment-experienced adults and children ≥4 weeks)
- component of preferred initial antiretroviral regimens
Contraindications
- concurrent dofetilide (CYP3A4/renal transporter interactions)
- concurrent pilsicainide (similar)
Adverse Effects
Common
- insomnia
- headache
- nausea
- elevated creatinine (inhibits tubular secretion — not true nephrotoxicity)
- elevated creatine kinase
Serious
- hypersensitivity reactions (rare — discontinue if suspected)
- neural tube defects (periconceptional exposure)
- immune reconstitution inflammatory syndrome (IRIS) upon initiation in advanced HIV
- hepatotoxicity (in those with HBV/HCV co-infection)
Pharmacokinetics (ADME)
| Absorption | ~70% bioavailability with or without food; take with food for highest levels |
| Distribution | Protein binding >98.9%; Vd ~17.4 L |
| Metabolism | UGT1A1 (primary), CYP3A4 (minor) |
| Excretion | Fecal (~53%) and renal (~31%); no renal dose adjustment needed |
| Half-life | 14 hours |
| Onset | Days to weeks for viral suppression |
| Peak | 2–3 hours |
| Duration | 24 hours |
| Protein Binding | >98.9% |
| Vd | ~17.4 L |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| polyvalent cations (antacids, calcium, iron, supplements) | chelation reduces dolutegravir absorption; take dolutegravir 2h before or 6h after cation-containing products | major |
| rifampin | UGT1A1/CYP3A4 induction reduces dolutegravir levels by ~54%; increase dose to 50 mg BID when co-administered with rifampin | major |
| metformin | dolutegravir inhibits renal OCT2/MATE1 transporters, increasing metformin levels up to 79%; adjust metformin dose | major |
Nursing Considerations
- Take with food (especially for resistant strains requiring twice-daily dosing); take 2 hours before or 6 hours after antacids, calcium, iron, or magnesium to prevent chelation-mediated absorption reduction
- For HIV-positive women who may become pregnant: counsel about the small (0.1%) but real risk of neural tube defects with periconceptional dolutegravir exposure; discuss risk-benefit; folic acid supplementation
- Apparent creatinine rise of 0.1–0.2 mg/dL is expected — dolutegravir inhibits tubular creatinine secretion without affecting true GFR; this should be recognized and not lead to dose adjustment
- Ensure HBV and HCV status are known before initiating antiretroviral therapy — coinfection significantly increases risk of hepatic complications
Clinical Pearls
- Dolutegravir has the highest genetic barrier to resistance of the INSTIs, owing to stacking interactions with Q148, G140, and Y143 residues — resistance mutations significantly impair viral fitness, making dolutegravir a preferred first-line agent per WHO global guidelines
- The Triumeq fixed-dose combination (dolutegravir/abacavir/lamivudine) requires HLA-B*5701 testing before initiation — HLA-B*5701-positive patients have a 5–8% risk of potentially fatal abacavir hypersensitivity reaction
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.