TOPICAL CORTICOSTEROIDS REVERSE THE ANTIVIRAL EFFECT OF TOPICAL CIDOFOVIR IN THE AD5-INOCULATED NEW-ZEALAND RABBIT OCULAR MODEL

Purpose. To determine how the addition of topical corticosteroids woul d affect the anti-adenoviral inhibitory. effect of topical cidofovir ( S-HPMPC) in the Ad5 New Zealand (Ad5/NZ) rabbit ocular model. Methods. In a series of experiments (two-eye design), Ad5-inoculated/NZ rabbit s (10(6) pfu/eye) were treated with 1 of 3 treatment regimens. Group 1 was administered 1% cidofovir (CDV) twice a day for 3 days plus comfo rt tears four times a day for 14 days. Group 2 was administered 1% CDV twice a day for 3 days plus 1% Pred Forte four times a day for 14 day s. Group 3 tvas administered vehicle twice a day for 3 days plus comfo rt tears four times a day for 14 days and served as the control. Al ey es were evaluated for 21 days for serial eye titers, Ad5 positive eyes , and duration of Ad5 shedding. Results. Compared to control eyes in t he Ad5/NZ rabbit ocular model, CDV alone demonstrated a significant an tiviral inhibitory effect: reduced mean Ad5 eye titer during the early phase of infection (days 3 to 7), fewer Ad5-positive eyes during the early and late (days 9 to 21) phases of infection, and shortened durat ion of shedding. However, concomitant treatment with both Pred Forte a nd CDV significantly reversed the antiviral inhibitory activity of CDV : increased mean Ad5 eve titer, increased Ad5-positive eyes (early and late phases) and prolonged duration of shedding. Conclusions. These e xperimental data further support the clinical development of cidofovir as a topical antiviral agent, but they do not support a treatment reg imen that includes a combination of topical corticosteroids and topica l cidofovir as a desirable strategy for the treatment of symptomatic a denoviral ocular infection.