Effect of Daily Zidovudine (AZT) Pulse-Therapy on Replication of Human Immunodeficiency Virus Type 1 and Type 2 in vitro

Abstract

Zidovudine (3′-azido-3′-deoxythymidine, azidothymidine) has demonstrated clinical efficacy in patients with acquired immunodeficiency syndrome (AIDS) and related disorders but toxicity often limits its use. Employing an in vitro cell-culture model we compared the antiviral effect and cytotoxicity of a single daily pulse exposure of 10 μm for 60 min with a continuous exposure of 1 μm. In patients these concentrations correspond approximately to a single oral daily dose of 1 g zidovudine and to a conventional oral zidovudine therapy with four to six daily doses, respectively. Replication of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) was inhibited in cultured peripheral blood mononuclear cells equally well with both regimens. No differences in cytotoxicity were observed and intracellular concentrations of zidovudine triphosphate were comparable. It is conceivable that single daily doses of zidovudine might be equally efficacious as several daily doses. Using single daily doses would facilitate patient compliance and the concept should therefore be explored in clinical trials.