EVALUATION OF CIDOFOVIR (HPMPC, GS-504) AGAINST ADENOVIRUS TYPE-5 INFECTION IN-VITRO AND IN A NEW-ZEALAND RABBIT OCULAR MODEL

The antiviral inhibitory activity of Cidofovir [(S)-3-hydroxy-2-(phosp honomethoxy)propyl]cytosine dihydrate, HPMPC, GS-504] against adenovir us type 5 (Ad5) in the New Zealand rabbit ocular replication model was evaluated. The 50% inhibitory dose (ID50) of Cidofovir was determined to be 4.7-9.5 mu g/ml against four adenoviruses (two Ad5, Ad8 and Ad1 4) by plaque reduction assay in A549 cells. Twenty-four New Zealand ra bbits received intrastromal inoculation and topical application of 2 x 10(6) plaque-forming units (PFU) per eye of Ad5 McEwen, a clinical is olate. Cidofovir was administered topically at three different concent rations twice per day, beginning 16 h postinoculation and continuing f or 20 consecutive days. The inhibitory effects were determined by meas uring suppression of virus replication and by observation of the clini cal effects. Compared to the placebo group, the 1% and 0.5% Cidofovir- treated groups showed significantly reduced Ad5 ocular titers, fewer d ays of viral shedding and less severe subepithelial opacities (P=0.000 1). The 1% Cidofovir group had the lowest humoral antibody titer again st adenovirus antigens, but the difference was not significant (P=0.24 ). Cidofovir proved to have potent antiviral activity against adenovir us replication and may have great promise for the treatment of adenovi rus infection. Further investigation is recommended.