Dolutegravir

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Dolutegravir is a second-generation integrase strand transfer inhibitor (INSTI) and a preferred first-line agent for HIV-1 treatment. It has a high barrier to resistance and is a component of several common fixed-dose combination tablets.[1]

Administration

  • Type: Integrase strand transfer inhibitor (INSTI)
  • Dosage Forms: 10 mg, 25 mg, 50 mg tablets; 5 mg dispersible tablets for oral suspension (Tivicay PD)
  • Routes of Administration: Oral
  • Common Trade Names: Tivicay, Tivicay PD; also in fixed-dose combinations: Triumeq (dolutegravir/abacavir/lamivudine), Juluca (dolutegravir/rilpivirine), Dovato (dolutegravir/lamivudine)

Adult Dosing

  • Treatment-naive or INSTI-naive: 50 mg PO once daily[1]
  • INSTI-experienced with suspected resistance: 50 mg PO twice daily[1]
  • With UGT1A/CYP3A inducers (e.g., efavirenz, rifampin, carbamazepine, phenytoin): 50 mg PO twice daily
  • Avoid coadministration with dofetilide (contraindicated)[1]
  • Take with or without food; separate from polyvalent cation-containing products (antacids, calcium, iron) by ≥2 hours before or ≥6 hours after[1]

Pediatric Dosing

  • Approved for patients ≥4 weeks and ≥3 kg[1]
  • Weight-based dosing; consult prescribing information or pediatric ID
  • Tivicay and Tivicay PD are not bioequivalent or interchangeable

Special Populations

Pregnancy Rating

  • Initial signal of increased neural tube defect (NTD) risk from Botswana (2018); subsequent larger studies show risk is comparable to other ARVs (~0.11%) and not increased in settings with folic acid fortification[2][3]
  • WHO and US guidelines now recommend dolutegravir can be used in pregnancy and in women of childbearing potential; counsel about NTD risk and ensure adequate folate[1]
  • Perform pregnancy testing before initiation in women of childbearing potential[1]
  • Antiretroviral Pregnancy Registry: 1-800-258-4263

Lactation risk

  • Present in human milk; counsel regarding risks of HIV transmission to breastfed infant and potential for adverse drug reactions[1]

Renal Dosing

  • Adult: No dose adjustment for mild, moderate, or severe renal impairment[1]
    • Not studied in dialysis patients
    • INSTI-experienced patients with severe renal impairment: Not recommended (decreased dolutegravir concentrations may lead to resistance)
  • Pediatric: No specific renal dose adjustment data

Hepatic Dosing

  • Adult: No dose adjustment for mild or moderate (Child-Pugh A or B) hepatic impairment[1]
    • Severe (Child-Pugh C): Not recommended (not studied)
  • Pediatric: Not studied

Contraindications

  • Allergy to class/drug
  • Coadministration with dofetilide (dolutegravir inhibits renal tubular secretion of dofetilide, increasing risk of serious arrhythmia)[1]

Adverse Reactions

Serious

  • Hypersensitivity reactions (rash, constitutional symptoms, organ dysfunction — discontinue immediately and do not rechallenge)[1]
  • Hepatotoxicity (higher rates of transaminase elevations in hepatitis B/C co-infected patients; hepatic flares may occur with IRIS)[1]
  • Neural tube defects with periconceptional exposure (see Pregnancy above)

Common

  • Insomnia, headache, fatigue[1]
  • Nausea, diarrhea
  • Serum creatinine elevation (~0.1–0.15 mg/dL increase) — this is due to inhibition of tubular creatinine secretion (OCT2), not actual nephrotoxicity; GFR is unaffected[1]

Pharmacology

  • Half-life: ~14 hours[4]
  • Metabolism: Primarily UGT1A1 (glucuronidation); minor CYP3A4 component. Substrate of UGT1A1, UGT1A3, UGT1A9, P-gp, and BCRP[1]
  • Excretion: ~53% feces (unchanged), ~31% urine (as metabolites); <1% unchanged in urine[1]

Mechanism of Action

  • Dolutegravir inhibits HIV-1 integrase by binding to the enzyme active site and blocking the strand transfer step of retroviral DNA integration into the host cell genome. This prevents insertion of HIV proviral DNA into host chromosomal DNA, a step essential for viral replication. Dolutegravir has a slow dissociative half-life from the integrase–DNA complex, contributing to its high barrier to resistance and sustained antiviral activity.[4][1]

Comments

  • Dolutegravir is among the most commonly prescribed ARVs; (standalone or in Triumeq, Juluca, or Dovato)
  • Creatinine pearl: Dolutegravir raises serum creatinine by ~0.1 mg/dL via OCT2 inhibition without true renal injury — do not reflexively attribute AKI to dolutegravir in the ED[1]
  • Antacid/cation interaction: Polyvalent cations (Mg, Al, Ca, Fe, Zn) chelate dolutegravir and reduce absorption. Separate dosing by ≥2 hours before or ≥6 hours after. This is relevant when administering antacids or supplements in the ED[1]
  • If hepatitis B/C co-infected, expect higher rates of transaminase flares early in therapy (IRIS effect); check hepatic panel if clinically indicated[1]
  • Overdose: No specific antidote; supportive care. Highly protein bound (~99%); unlikely removed by dialysis[1]
  • Avoid St. John's wort and oxcarbazepine (decrease dolutegravir levels)[1]

See Also

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 Tivicay (dolutegravir) [prescribing information]. Research Triangle Park, NC: ViiV Healthcare; 2024.
  2. ↑ Zash R, et al. Update on neural tube defects with antiretroviral exposure in the Tsepamo study, Botswana. 24th International AIDS Conference, 2022. Abstract PELBB02.
  3. ↑ Simeone RM, et al. Dolutegravir and pregnancy outcomes including neural tube defects in the USA during 2008-20: a national cohort study. Lancet HIV. 2023;10(9):e588-e596.
  4. ↑ 4.0 4.1 Dolutegravir. DrugBank. Accessed 2025.
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