Zidovudine-induced fever

Abstract

Zidovudine (3'-azido-3'deoxythymidine, AZT, Retrovir) is the first antiretroviral drug to demonstrate clinical efficacy for symptomatic human immunodeficiency virus infection. In a large, placebo-controlled trial, nausea and hematologic toxicity, but not fever, occurred more frequently in zidovudine- than in placebo-treated patients. However, in an open label study, fever severe enough to halt zidovudine administration occurred in 10% of 70 acquired immune deficiency syndrome (AIDS) patients receiving the drug. We now describe three AIDS patients with severe zidovudine-induced fever in whom other causes of fever were excluded. Zidovudine-induced fever was confirmed in each case by drug rechallenge. Using an enzyme immunoassay, we detected IgM antibodies directed against a zidovudine-serum protein conformational determinant in one of these three patients. Neither IgG nor IgM anti-zidovudine antibodies were present in sera from the other two patients with zidovudine fever, from four AIDS patients who discontinued zidovudine for reasons other than fever, or from five AIDS patients who never received zidovudine. Zidovudine may cause fever as a severe adverse effect in patients with AIDS. Either type III or type IV hypersensitivity may mediate this reaction.