Integrase strand-transfer inhibitor (INSTI) — antiretroviral Pregnancy: First-line in pregnancy and pre-conception (WHO 2019, EACS 2024). Earlier NTD signal (Tsepamo Botswana — NEJM 2018) refined to small absolute risk (~0.1%) by larger datasets.

Dolutegravir

Brand names: Tivicay, Triumeq (with abacavir + lamivudine), Juluca (with rilpivirine), Dovato (with lamivudine)

Adult dose

Dose: Treatment-naïve / experienced (no INSTI resistance): 50 mg OD. With CYP3A4/UGT1A1 inducers (rifampicin, carbamazepine, phenytoin, efavirenz): 50 mg BD. Treatment-experienced with documented INSTI resistance: 50 mg BD.

Route: Oral

Frequency: Once daily (BD if INSTI resistance or strong inducer co-administered)

Max: 100 mg/day

Take with or without food (food slightly increases AUC — useful with rifampicin to mitigate interaction). With multivalent cation–containing antacids/iron/calcium: take dolutegravir 2 hours before or 6 hours after.

Paediatric dose

Route: Oral

Frequency: Once daily

≥6 yrs and ≥14 kg (per WHO 2019): 14–<20 kg 30 mg OD (dispersible 5 mg tablets); 20–<25 kg 35 mg OD; 25–<30 kg 40 mg OD; 30–<40 kg 45 mg OD; ≥40 kg 50 mg OD.

Dose adjustments

Renal

No adjustment in mild–moderate impairment. Severe (CrCl <30): caution; AUC ↑ ~30%.

Hepatic

Mild–moderate: no adjustment. Severe (Child-Pugh C): not recommended.

Clinical pearls

Now the WHO and BHIVA preferred 1st-line ART backbone (with abacavir/lamivudine = Triumeq, or with tenofovir/lamivudine, or 2-drug Dovato). Rapid viral suppression, high genetic barrier, well-tolerated.
INSTI-related weight gain (3–5 kg in first 6 months, more in women, Black ethnicity, baseline higher BMI) — counsel and link with diet/exercise advice; rarely sufficient reason to switch.
Creatinine rise of 10–15 µmol/L in first 2–4 weeks is benign tubular-secretion inhibition (NOT true GFR loss). Confirm with cystatin C if uncertain. Stable thereafter.
Pregnancy: WHO 2019 and EACS 2024 confirm dolutegravir is first-line throughout pregnancy and in women of childbearing potential — initial Tsepamo NTD signal has not been replicated at significant magnitude.
Two-drug regimens (Dovato, Juluca) reduce drug burden — use only after careful screening for resistance and HBV co-infection (lamivudine alone has weak HBV cover).
Insomnia / mood disturbance is the leading cause of dolutegravir discontinuation — switching to bictegravir or doravirine often resolves.

Contraindications

Concurrent dofetilide (↑ dofetilide concentrations — torsades risk)
Hypersensitivity to dolutegravir

Side effects

Insomnia, vivid dreams, anxiety, depression (uncommon but distinctive — may need switch)
Headache, dizziness, fatigue
Nausea, diarrhoea
Weight gain (~3–5 kg first 6 months — INSTI class effect, dolutegravir/bictegravir > raltegravir > elvitegravir)
Modest creatinine rise (~10–15 µmol/L within 4 weeks — competitive inhibition of OCT2/MATE1 tubular secretion; non-progressive, not true GFR loss)
Hepatotoxicity (rare, but ↑ in HBV/HCV co-infection)
Hypersensitivity reactions (rare)
Neural tube defects — initial Tsepamo signal (NEJM 2018) of ↑ NTD with periconceptional exposure has been refined: latest data show small absolute risk (~0.1–0.2% above background); WHO 2019 and EACS 2024 now consider dolutegravir SAFE first-line in pregnancy and women of childbearing potential

Interactions

Multivalent cations (Mg, Al, Ca, iron — antacids, supplements, calcium): chelate dolutegravir → therapeutic failure. Separate by 2 hours before / 6 hours after.
Rifampicin: ↓ dolutegravir — increase to 50 mg BD. Avoid rifabutin substitution unless contraindication.
Carbamazepine, phenytoin, phenobarbital: ↓ dolutegravir — switch antiepileptic if possible; otherwise 50 mg BD.
Efavirenz, nevirapine: ↓ dolutegravir — 50 mg BD (and consider switching ART backbone).
Metformin: ↑ metformin AUC ~80% (OCT2 inhibition) — limit metformin to 1 g/day; monitor lactate if eGFR <60.
Dofetilide: contraindicated.
St John's wort: ↓ levels — avoid.

Monitoring

HIV RNA at week 4 and 12, then 3-monthly
CD4 every 3–6 months
Creatinine, electrolytes at baseline, week 4, then 3-monthly
LFTs at baseline, week 4, 3-monthly
Lipids and HbA1c annually
Weight, BP, mood at every visit

Reference: BNFc; BNF 90; SmPC Tivicay / Triumeq / Dovato; BHIVA Adult HIV Guidelines 2022; EACS Guidelines 12.0 (2024); WHO Consolidated ART Guidelines 2021; Tsepamo NEJM 2019;381:827; SINGLE / SPRING-2 / FLAMINGO trials. Verify against your local formulary and the latest BNF before prescribing.

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways