Dolutegravir is a second-generation integrase strand transfer inhibitor (INSTI) used as a core agent in combination antiretroviral therapy (ART) for the treatment of HIV-1 infection. It is characterized by a high genetic barrier to resistance, once-daily dosing without a pharmacokinetic booster, and a favorable safety profile. It is a first-line and second-line agent recommended by the National AIDS Control Organisation (NACO) in India.
Adult: 50 mg once daily, with or without food. For treatment-experienced patients with certain INSTI-associated resistance mutations or suspected resistance, the dose is 50 mg twice daily.
Note: Tablet should be swallowed whole with water. Can be taken with or without food. If co-administered with polyvalent cation supplements (Ca, Mg, Fe) or antacids, administer dolutegravir 2 hours before or 6 hours after these products. If taken with food, it can be administered simultaneously with a calcium or iron supplement.
Dolutegravir selectively inhibits the catalytic activity of HIV-1 integrase, an enzyme essential for viral replication. It binds to the integrase active site and blocks the strand transfer step, preventing the integration of viral DNA into the host genome. This halts the formation of the HIV-1 provirus and subsequent viral replication.
Pregnancy: Previously associated with a potential increased risk of neural tube defects (NTDs) when used at conception and in early pregnancy. Current WHO and NACO guidelines state it can be used throughout pregnancy and in women of childbearing potential, provided they are on effective contraception and the benefits outweigh risks. Pregnancy registry enrollment is recommended.
Driving: Dizziness and fatigue have been reported. Patients should be cautioned about operating machinery or driving if they experience these effects.
| Metformin | Dolutegravir may increase metformin exposure. Monitor blood glucose and consider metformin dose reduction. | Moderate |
| Rifampicin/Rifabutin | Strong UGT1A1/CYP3A inducers reduce dolutegravir levels. Dose adjustment to 50 mg twice daily is required with rifampicin. | Major |
| Carbamazepine, Phenytoin, Phenobarbital | Enzyme inducers may reduce dolutegravir levels. Consider alternative anticonvulsant or increase dolutegravir to 50 mg twice daily. | Major |
| Calcium, Magnesium, Iron supplements/Antacids | Cation-containing products chelate dolutegravir, reducing absorption. Administer dolutegravir 2 hours before or 6 hours after these products. | Major |
| Etravirine (without boosted PI) | May reduce dolutegravir levels. Avoid co-administration unless with boosted darunavir or lopinavir. | Moderate |
| Dofetilide | Dolutegravir may increase dofetilide levels, risking serious arrhythmias. Contraindicated. | Contraindicated |
Same composition (Dolutegravir (50mg)), different brands: