Evaluation of intravenous zanamivir against experimental influenza A (H5N1) virus infection in cynomolgus macaques

We investigated the prophylactic and therapeutic efficacy of an intravenous (IV) formulation of zanamivir in a macaque infection model for highly pathogenic influenza A (H5N1) virus. Antiviral efficacy was dose-dependent, with no reduction in viral load observed at 2 mg/kg, but a significant reduction observed at 10 mg/kg (p = 0.039) and at 20 mg/kg in the combined prophylactic and therapeutic groups (p = 0.049) with both prophylaxis (commencing 12 h before infection) and therapy (commencing 4 h after infection) showing similar reductions in viral load. Combined gross pathology and microscopic pneumonia scores in the treated animals relative to untreated controls were significantly reduced at 10 mg/kg (p = 0.02) and at 20 mg/kg in the prophylaxis group (p, = 0.02), but were not significant in the treatment group (p = 0.145). in this new animal model for evaluation of influenza antivirals, despite variability observed between individual animals, IV zanamivir showed evidence of efficacy against highly pathogenic H5N1 virus. (C) 2008 Elsevier B.V. All rights reserved.