A 28-year-old HIV-positive patient is initiated on a regimen including zidovudine (AZT). The dose-limiting toxicity of zidovudine that often necessitates switching therapy is:

• A Peripheral neuropathy from mitochondrial DNA polymerase inhibition
• B Hepatic steatosis from fatty acid beta-oxidation inhibition
• C Bone marrow suppression causing macrocytic anemia and neutropenia ✓
• D Pancreatitis from accumulation of zidovudine triphosphate

Explanation

Zidovudine's dose-limiting toxicity is bone marrow suppression, manifesting as macrocytic anemia (most common) and neutropenia, requiring blood transfusions or granulocyte colony-stimulating factor in severe cases. Macrocytosis occurs because zidovudine incorporates into mitochondrial DNA of erythroid precursors. Peripheral neuropathy and pancreatitis are more characteristic of stavudine and didanosine, respectively. Lactic acidosis with hepatic steatosis is a class effect of NRTIs but particularly associated with stavudine.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.