Effect of famciclovir on herpes simplex virus type 1 corneal disease and establishment of latency in rabbits

Famciclovir (FCV) is efficacious in the treatment of acute herpes tester an d recurrent genital infections but has not been used to treat ocular herpes simplex virus (HSV) infections. We evaluated the efficacy of orally admini stered FCV in treating HSV-1 epithelial keratitis and determined its effect s on the establishment of latency and subsequent reactivation. Rabbits were inoculated with HSV-1 strain 17 syn+ and treated twice daily with increasi ng concentrations of FCV (60 to 500 mg/kg of body weight). This resulted in a significant, dose dependent improvement in keratitis scores, as well as prolonged survival. Regardless of the dose of drug used, all groups exhibit ed the high rates of spontaneous and induced reactivation characteristic of 17syn+. The efficacy of 250 mg of FCV per kg was also compared to topical treatment with 1% trifluorothymidine (TFT). Although TET treatment was more effective at reducing eye disease, FCV-treated rabbits had a better surviv al rate. Real-time quantitative PCR analysis of rabbit trigeminal ganglia ( TG) demonstrated that FCV significantly reduced the HSV-1 copy number compa red to that after treatment with TFT or the placebo but not in a dose-depen dent manner. In summary, oral FCV treatment significantly reduces the sever ity of corneal lesions, reduces the number of HSV-1 genomes in the TG, impr oves survival, and therefore may be beneficial in reducing the morbidity of HSV keratitis in the clinic.