Pharmacology · Integrase strand transfer inhibitors (INSTIs)
Dolutegravir !
A high-barrier integrase inhibitor, the backbone of WHO's preferred treatment for all populations, including pregnant women.
Updated 2026-11-01
Also called: DTG
The figure shows dolutegravir bound to the two-magnesium active site of the HIV-1 intasome (integrase bound to the end of viral DNA), by cryo-electron microscopy.
Mechanism of action
It binds the two magnesium ions in the integrase active site once the enzyme holds the end of viral DNA, and displaces that end, so viral DNA cannot be inserted into the cell's chromosome. It comes off the enzyme very slowly, which explains its high genetic barrier.
- Integrase holds the end of viral DNA (intasome)
- Dolutegravir binds the two magnesium ions of the active site
- Strand transfer is blocked
- Viral DNA is not integrated into the chromosome
Pharmacokinetics
- Absorption
- Oral, with or without food; polyvalent cations reduce absorption
- Metabolism
- Liver, mainly by UGT1A1 and partly by CYP3A
- Half-life
- Allows once-daily dosing in most patients
Indications
- HIV-1 infection, as preferred first- and second-line treatment, combined with two NRTIs HIV infection and AIDS →
Adverse effects
Common
- Insomnia
- Headache
- Tiredness
- Weight gain with long-term use
- Mild creatinine rise without kidney damage
Contraindications
- Previous hypersensitivity to dolutegravir
- Use with dofetilide
Key interactions
- Aluminium or magnesium antacids, calcium or iron supplements
- They chelate the drug and lower absorption: doses are separated
- Metformin
- Dolutegravir inhibits OCT2 and MATE1 and raises metformin; glucose and tolerance are watched
- Rifampicin
- Induces UGT1A1 and CYP3A and lowers dolutegravir: needs an adjustment ordered by the team (TB co-infection)
- Dofetilide
- Raises dofetilide with risk of serious arrhythmias: contraindicated
What is monitored
- Viral load and CD4
- Weight and metabolic factors
- Baseline creatinine (expect a small stable rise)
- Liver tests in hepatitis co-infection
Administration and safety
- By mouth, with or without food; there is a dispersible tablet for children that is not interchangeable with the film-coated tablet
- Separate antacids, calcium, iron and mineral-containing multivitamins in time, as the label directs
- Widely used within the fixed combination with lamivudine and tenofovir (TLD)
Nursing care
- Ask about antacids, iron, calcium and supplements
- In diabetes on metformin, watch glucose and gut symptoms
- If on rifampicin TB treatment, confirm the regimen adjustment
- Reinforce adherence and viral load checks
Pregnancy and breastfeeding
WHO recommends it as preferred treatment also in pregnant women and women of childbearing potential: newer data show the neural tube defect risk is much lower than early studies suggested.
Test yourself
Think of the answer, then tap the question to see it.
Why does dolutegravir raise creatinine without harming the kidney?
It inhibits the tubular OCT2 transporter that secretes creatinine; true glomerular filtration does not change.
Which antidiabetic interaction should be remembered with dolutegravir?
It raises metformin levels by inhibiting OCT2 and MATE1.
What does WHO recommend about dolutegravir in pregnancy?
It recommends it as preferred treatment for all populations, including pregnant women, because the neural tube defect risk proved much lower than first suggested.
What does dolutegravir bind in the integrase active site?
The two catalytic magnesium ions, in the complex of integrase with viral DNA.
Related drugs
Related conditions
← Back to the class: Integrase strand transfer inhibitors (INSTIs)
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: Dolutegravir: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2025); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026); WHO recommends dolutegravir as preferred HIV treatment option in all populations (World Health Organization, 2019); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 64 (McGraw Hill, 2023).
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Representative model, for educational purposes only.