Comparative antiviral efficacies of cidofovir, trifluridine, and acyclovirin the HSV-1 rabbit keratitis model

PURPOSE TO determine the relative antiviral inhibitory activity of topical 1% and 0.5% cidofovir, topical trifluridine (Viroptic; Burroughs-Wellcome, Research Triangle Park, NC), and topical acyclovir (Zovirax; The Wellcome F oundation, London, UK) during a 7-day period for the treatment of herpes si mplex virus type 1 (HSV-1) keratitis and HSV-I replication in the New Zeala nd rabbit ocular model. METHODS. In a series of four experiments using a tn two-eye design, a total of 80 NeW Zealand rabbits were inoculated in both eyes with HSV-1 McKrae a fter epithelial scarification. forty-eight hours after inoculation, the rab bits were randomly assigned to a treatment group. Five treatment groups (16 rabits/group) were evaluated; I, 1% cidofovir, twice daily for 7 days; II 0.5% cidofovir, twice daily for 7 days; III, 3% acyclovir ointment, five ti mes daily for 7 days; IV, 1% trifluridine, nine times daily for 3 days, the n 4 times daily for 4 days; and V, control vehicle twice daily for 7 days. HSV-1 dendritic keratitis was graded in a masked fashion by slit-lamp exami nation on days 2, 3, 5, 7, 9, 11, and 1;I. Ocular viral cultures were obtai ned after slit-lamp examination on days 1, 3, 5, 7, 9, 11, and 14. REULTS. Compared with the control group, all four treatment groups demonstr ated significantly lower viral titers, fewer HSV-1-positive eyes/total duri ng the treatment period, lower keratitis treatment groups, the 1% and 0.5% cidofovir treatments were significantly more effective than treatment group s, the 1% and 0.5% cidofovir treatments were significantly more effective t han acyclovir and trifluridine as measured by the previous viral and kerati tis parameters. CONCLUSIONS. Topical 1% and 0.5% cidofovir both appeared to be significantl y more efficacious than topical trifluridine and acyclovir, during a 7-day course, in the treatment of experimental HSV-1 ocular disease in the New Ze aland rabbit keratitis model.