dolutegravir

Dolutegravir is an antiretroviral medication in the integrase strand transfer inhibitors (INSTIs) class used to treat HIV-1 infection. It works by inhibiting the HIV integrase enzyme, which prevents the viral DNA from integrating into the host genome and thereby blocks viral replication. Dolutegravir is commonly used as part of combination antiretroviral therapy and is available in multiple tablet formulations, including fixed-dose combinations with other agents.

Indications and formulations include use in treatment-naive and certain treatment-experienced adults and some pediatric patients. Fixed-dose combinations such as dolutegravir/lamivudine and dolutegravir/abacavir/lamivudine (Triumeq) are widely prescribed. Dosing is typically once daily, though co-administration with rifampin may require twice-daily dosing. Dolutegravir should be separated from polyvalent cations (calcium, iron, magnesium) by several hours to avoid reduced absorption.

Pharmacology and pharmacokinetics: dolutegravir is absorbed orally and has a half-life of about 13–14 hours, supporting once-daily dosing in many regimens. It is primarily metabolized by UGT1A1 with minor involvement of other pathways and is excreted in urine and feces as metabolites. Drug interactions are relatively limited but notable; coadministration with polyvalent cations can decrease absorption, and rifampin reduces dolutegravir plasma levels.

Safety and adverse effects: dolutegravir is generally well tolerated. Common side effects include insomnia, headache, and nausea, with potential weight gain in some patients. Serious but rare adverse events can include hypersensitivity reactions and hepatotoxicity. Safety in pregnancy has been scrutinized; initial signals of a neural tube defect risk at conception prompted careful assessment, and current practice emphasizes individualized risk-benefit discussions in pregnant people. Dolutegravir maintains a high barrier to resistance and is a preferred option in many HIV treatment guidelines.