EVIDENCE THAT HIGH-DOSAGE ZIDOVUDINE AT TIME OF RETROVIRUS EXPOSURE REDUCES ANTIVIRAL EFFICACY

The antiviral efficacy of prophylactic 3'-azido-3'-deoxythymidine (AZT ) therapy administered by continuous infusion or intermittent injectio n was compared in pediatric cats infected with feline leukemia virus. A 4-week treatment regimen of AZT was initiated at -48, 8, or 96 h pos tinfection (p.i.). For AZT therapy begun at -48 h p.i., significant ef ficacy was attained when therapy was given by continuous infusion but not by intermittent injection. However, when AZT therapy was delayed u ntil 96 h p.i., both continuous infusion and intermittent injection ga ve complete protection. The results suggest that intermittent AZT admi nistration is less efficacious than continuous infusion, Higher peak A ZT concentrations in plasma associated,vith intermittent injection com pared with those associated,vith continuous infusion may be immunotoxi c, thus reducing the drug-induced vaccine effect. Furthermore, AZT tox icity seemed to be restricted to a window of sensitivity close to the time of virus challenge because delaying the start of AZT therapy unti l 96 h p.i, was highly efficacious, regardless of the method of admini stration.