Topical corticosteroids reverse the antiviral effect of topical cidofovir in the Ad5-inoculated New Zealand rabbit ocular model.
OBJECTIVE
To determine how the addition of topical corticosteroids would 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 rabbits (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 comfort 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 days. Group 3 was administered vehicle twice a day for 3 days plus comfort tears four times a day for 14 days and served as the control. All eyes were evaluated for 21 days for serial eye titers, Ad5 positive eyes, and duration of Ad5 shedding.


RESULTS
Compared to control eyes in the Ad5/NZ rabbit ocular model, CDV alone demonstrated a significant antiviral 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 duration of shedding. However, concomitant treatment with both Pred Forte and CDV significantly reversed the antiviral inhibitory activity of CDV: increased mean Ad5 eye titer, increased Ad5-positive eyes (early and late phases) and prolonged duration of shedding.


CONCLUSIONS
These experimental data further support the clinical development of cidofovoir as a topical antiviral agent, but they do not support a treatment regimen that includes a combination of topical corticosteroids and topical cidofovir as a desirable strategy for the treatment of symptomatic adenoviral ocular infection.
Romanowski
E G
EG
Department of Ophthalmology, University of Pittsburgh School of Medicine, Pennsylvania, USA.
Araullo-Cruz
T
T
Gordon
Y J
YJ
D000258:Adenovirus Infections, Human / Q000188:drug therapy*; D000260:Adenoviruses, Human / Q000302:isolation & purification / Q000502:physiology; D000287:Administration, Topical; D000818:Animals; D000998:Antiviral Agents / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000077404:Cidofovir; D003228:Conjunctiva / Q000821:virology; D003236:Conjunctivitis, Viral / Q000188:drug therapy*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004359:Drug Therapy, Combination; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011239:Prednisolone / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D005938:Glucocorticoids; D009883:Ophthalmic Solutions; D063065:Organophosphonates; D009943:Organophosphorus Compounds; C009935:prednisolone acetate; D003596:Cytosine; D011239:Prednisolone; D000077404:Cidofovir