azidotimidin

Azidotimidin, also known as azidothymidine or AZT, is a synthetic nucleoside analog of thymidine in which the 3'-hydroxyl group of the deoxyribose sugar is replaced by an azido group. It is an antiretroviral medication and belongs to the class of nucleoside reverse transcriptase inhibitors (NRTIs).

Mechanism of action: After cellular phosphorylation to the active triphosphate form, azidotimidin triphosphate competes with deoxythymidine triphosphate for incorporation by HIV reverse transcriptase. Once incorporated into viral DNA, the 3'-azido group prevents formation of the next phosphodiester bond, causing chain termination and inhibition of viral DNA synthesis.

History and medical use: Azidotimidin was first synthesized in the 1960s and was later repurposed as an antiviral agent. It was approved by the U.S. Food and Drug Administration for the treatment of HIV infection in 1987 and became a foundational drug in combination antiretroviral therapy. It is commonly used as part of highly active antiretroviral therapy (HAART) regimens to reduce viral load and improve immune function.

Pharmacology and safety: AZT is administered orally and is phosphorylated intracellularly to its active triphosphate. It can cross the placenta. Common adverse effects include hematologic toxicity (notably anemia and neutropenia), fatigue, and headache. Long-term use carries a risk of mitochondrial toxicity, lactic acidosis, and hepatic steatosis. Drug interactions and cumulative toxicities with other NRTIs are considerations in treatment planning. Pregnant individuals may receive AZT to reduce mother-to-child transmission of HIV under clinical guidance.

See also: Zidovudine.