AZT

AZT, also known as zidovudine or 3'-azido-3'-deoxythymidine, is an antiretroviral medication used to treat HIV-1 infection and to reduce the risk of mother-to-child transmission. It is a nucleoside reverse transcriptase inhibitor (NRTI) and was the first antiretroviral approved for clinical use.

Mechanism of action: AZT is a thymidine analogue that is phosphorylated inside cells to the active triphosphate form (AZTTP). HIV reverse transcriptase incorporates AZTTP into viral DNA, but the molecule lacks a 3' hydroxyl group, causing chain termination and inhibition of viral replication. Resistance can arise through mutations in reverse transcriptase that lessen AZTTP incorporation or enhance excision of incorporated AZT.

Medical uses: AZT is used as part of combination antiretroviral therapy for HIV-1 infection in adults and children. It is also employed to reduce perinatal HIV transmission when given to the mother during pregnancy and labor and to the newborn, and is used in some post-exposure prophylaxis regimens.

Adverse effects and safety: Common adverse effects include bone marrow suppression with anemia and neutropenia, macrocytosis, fatigue, nausea, and headache. Long-term use can be associated with lactic acidosis and hepatic steatosis due to mitochondrial toxicity. Hematologic toxicity can be worsened by other myelosuppressive drugs. Liver or cardiac toxicity is uncommon but monitored, especially with prolonged therapy.

Pharmacokinetics: AZT is administered orally and has variable bioavailability. It crosses the blood–brain barrier and distributes to various tissues. It is metabolized mainly in the liver and eliminated primarily by the kidneys; dosing may require adjustment for renal impairment.

History: AZT was discovered by Jerome Horwitz in 1964 as a potential anticancer agent. It was repurposed for HIV in the 1980s and received FDA approval in 1987, becoming the first widely used antiretroviral drug.