Effects of acyclovir therapy during simultaneous reactivation of latent HSV-1 in rabbits

Acyclovir (ACV) therapy with a simultaneous reactivation of latent HSV-1 was evaluated in HSV-1 infected rabbit eyes. When the latently infected rabbits received epinephrine iontophoresis into corneas without ACV therapy 100% of eyes shed virus into tear film. The shedding was initiated on the second day of the epinephrine iontophoresis and lasted for an average of 4.6 days. When the rabbits received ACV (60 mg/kg body weight) intravenously once daily and topically (5% ACV ointment) twice daily for 6 consecutive days while a 0.01% epinephrine solution was iontophoresed into cornea for the first 3 consecutive days, 33% (2/6) of eyes showed detectable HSV-1 in the tear film only after terminating the ACV therapy, and the duration of shedding was for only one day. The average quantity of virus detectable in the tear film was decreased 14-fold in the latter group compared to the epinephrine iontophoresis group without ACV therapy. Four days after the last ACV therapy the titer of HSV-1 in the cell-free homogenates of the trigeminal and superior cervical ganglia was determined. For the epinephrine iontophoresed group, 67% of ganglia (8/12) were HSV-1 positive, while only 33% (4/12) of the ganglia from the combined treatment group were HSV-1 positive. The difference was statistically significant (p = 0.034). Furthermore, the titer of virus detectable in the cell-free homogenates of the virus-positive ganglia from the combined treatment group was less than that from the ganglia of the epinephrine iontophoresed group or untreated group. This suggests a reduction in the total number of latent foci for the combined treatment group.