Efficacy of topical cidofovir on multiple adenoviral serotypes in the New Zealand rabbit ocular model

PURPOSE: The goal of the present study was to determine the efficacy of topical 0.5% cidofovir twice daily for 7 days on the replication of multiple adenovirus (Ad) serotypes of subgroup C (Ad1, Ad5, Ad6) in the New Zealand rabbit ocular model. METHODs: In duplicate experiments for each serotype, a total of 20 rabbits (Ad5) or 16 rabbits each (Ad1 and Ad6) were inoculated topically in both eyes, with 1.5 X 10(6) pfu/eye of the appropriate virus. Twenty-four hours later, the rabbits in each serotype group were randomly divided into two topical treatment groups: I, 0.5% cidofovir; II, control vehicle. Treatment was twice daily for 7 days. All eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. RESULTS: Compared to the control, treatment with 0.5% cidofovir reduced the following: mean Ad titer (days 1 to 7) for Ad1 (6.3 +/- 20 x 10(1) versus 2.5 +/- 3.9 X 102 pfu/ml; P < 0.0003), Ad5 (3.4 +/-5.8 x 102 versus 1.6 +/- 2.0 x 10(3) pfu/ml; P < 0.000001), and Ad6 (1.2 +/- 5.1 x 10(2) versus 5.5 +/-14 x 10(2) pfu/ml; P = 0.015); reduced Ad-positive eyes/total for Adl [45/128 (35%) versus 84/128 (66%); P = 0.000002], Ad5 [84/160 (53%) versus 131/152 (86%); P < 0.000001], and Ad6 [36/128 (28%) versus 82/128 (64%); P < 0.000001]: and reduced the duration of Ad shedding forAdl (4.9 +/-1.9 versus 9.3 +/- 3.3 days; P < 0.00007), Ad5 (6.4 +/- 2.8 versus 11.5 +/- 2.3 days; P < 0.0001), and Ad6 (4.4 +/- 2.1 versus 8.4 +/- 2.5 days; P < 0.00004). CONCLUSIONS: Topical 0.5% cidofovir twice daily for 7 days demonstrated significant antiviral activity against multiple adenoviral serotypes (Ad1, Ad5, and Ad6) in the New Zealand rabbit ocular model. These in vivo data expand in vitro studies indicating the efficacy of cidofovir against different adenovirus serotypes and support its use in clinical trials.