Effect of 3′azidothymidine administered in drinking water or by continuous infusion on the development of MAIDS

Abstract

LP-BM5 MuLV infection of C57BL/6 mice induces a well characterized, lymphoproliferative, immunodeficiency disease (MAIDS), which is useful for evaluation of potential antiviral agents, because of the reproducibility of virological and clinical endpoints. This MAIDS retrovirus model was used to evaluate 3′azido-2,3′dideoxythymidine (AZT), using different doses, methods of administration and timing for initiation and continuation of therapy. AZT therapy 1 mg/ml in the drinking water given 30 days prior to virus challenge, and continued for 16 weeks, prevented LP-BM5 MuLV dissemination and disease in 13 of 15 treated mice. Efficacy was dose dependent for AZT concentrations of 1, 0.5, and 0.1 mg/ml in drinking water. One mg/ml AZT was most effective in preventing infection if therapy was begun within days prior to virus challenge or within the first four hours after virus inoculation. If treatment was initiated later, disease was delayed. Continuous infusion of AZT, 25 μg/h, was effective since virus was not detected in spleens of any mice during the 21 days of AZT treatment. However, after treatment was stopped treated mice became virus positive and disease progressed. Likewise, AZT administration at 1 mg/ml in the drinking water for only 21 days post virus inoculation (p.i.), was not sufficient to prevent virus dissemination or disease.