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1.
Am J Vet Res ; 80(5): 490-497, 2019 May.
Article in English | MEDLINE | ID: mdl-31034270

ABSTRACT

OBJECTIVE: To determine the effects of orally administered raltegravir in cats with experimentally induced ocular and respiratory feline herpesvirus-1 (FHV-1) infection. ANIMALS: 14 healthy 6-month-old unvaccinated specific pathogen-free cats. PROCEDURES: On day 0, all cats were experimentally inoculated by topical application of 0.1 mL of a solution containing 106 plaque-forming units of FHV-1 strain FH2CS to the inferior conjunctival fornix of each eye. Cats were randomly assigned to receive either raltegravir (80 mg; n = 7) or lactose (250 mg; vehicle; 7), PO, every 12 hours for 14 days beginning on day 1. Cats were assigned clinical ocular and respiratory disease scores every other day from days 0 to 30. Conjunctival swab specimens were collected for detection of FHV-1 by virus isolation and real-time PCR assay at 3-day intervals from days 0 to 30. Confocal microscopy was performed on days 0 and 10 to assess corneal epithelial leukocyte infiltration. The assessed variables and duration of FHV-1 shedding were compared between the 2 treatment groups. RESULTS: Cats in both groups developed moderate to severe conjunctivitis and ulcerative keratitis characteristic of FHV-1 infection. Median duration of FHV-1 shedding was shorter and signs of ocular and respiratory disease were less severe for raltegravir-treated cats than for vehicle-treated cats. However, the mean conjunctival FHV-1 titer and corneal epithelial leukocyte count did not differ between the 2 groups. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested orally administered raltegravir might be effective for alleviation of ocular and respiratory signs of FHV-1 infection in cats. (Am J Vet Res 2019;80:490-497).


Subject(s)
Antiviral Agents/therapeutic use , Cat Diseases/drug therapy , Conjunctivitis, Viral/veterinary , Herpesviridae Infections/veterinary , Raltegravir Potassium/therapeutic use , Respiratory Tract Infections/veterinary , Varicellovirus , Animals , Cat Diseases/virology , Cats , Conjunctivitis, Viral/drug therapy , Herpesviridae Infections/drug therapy , Random Allocation , Respiratory Tract Infections/drug therapy , Respiratory Tract Infections/virology , Single-Blind Method , Specific Pathogen-Free Organisms
2.
J Ocul Pharmacol Ther ; 31(10): 642-9, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26418618

ABSTRACT

PURPOSE: The effects of cidofovir were investigated against canine herpesvirus-1 (CHV-1) in vitro and in dogs with experimentally induced recurrent ocular CHV-1 infection, a host-adapted pathogen animal model of ocular herpes simplex virus-1 (HSV-1) infection. METHODS: The cidofovir EC50 was determined for CHV-1 and HSV-1. A randomized, masked vehicle-controlled trial was performed using beagles with experimentally induced recurrent ocular CHV-1 infection. Dogs received 1 drop of 0.5% cidofovir solution or 0.9% sodium chloride solution (vehicle) in both eyes 2 times daily for 14 days. Dogs were monitored at intervals for 30 days by a clinical ophthalmic examination, in vivo confocal microscopy of the cornea and conjunctiva, ocular sample CHV-1 polymerase chain reaction assay, hemogram, and serum biochemistry panel. Clinical ocular disease scores were calculated and infiltrating leukocytes detected by in vivo confocal microscopy quantified. RESULTS: Cidofovir displayed similar in vitro antiviral activity against CHV-1 and HSV-1. Clinical ocular disease scores were significantly higher in the cidofovir group compared to the vehicle group. Marked conjunctival pigmentation and blepharitis were also detected in the cidofovir group, but not the vehicle group. Conjunctival and corneal leukocyte infiltration scores determined by in vivo confocal microscopy were significantly higher in the cidofovir group. Dogs administered cidofovir had significantly reduced durations of ocular viral shedding compared to the vehicle group. Hemogram and serum biochemistry panel values were unremarkable. CONCLUSIONS: Twice-daily application of topical 0.5% cidofovir ophthalmic solution reduced the duration of ocular viral shedding in dogs with experimentally induced recurrent ocular CHV-1 infection, but was associated with local ocular toxicity.


Subject(s)
Cytosine/analogs & derivatives , Dog Diseases/virology , Herpesviridae Infections/drug therapy , Herpesvirus 1, Canid/drug effects , Organophosphonates/pharmacology , Administration, Ophthalmic , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/pharmacology , Antiviral Agents/toxicity , Chlorocebus aethiops , Cidofovir , Cytosine/administration & dosage , Cytosine/pharmacology , Cytosine/toxicity , Disease Models, Animal , Dogs , Herpesviridae Infections/virology , Madin Darby Canine Kidney Cells , Microscopy, Confocal , Organophosphonates/administration & dosage , Organophosphonates/toxicity , Random Allocation , Vero Cells , Virus Shedding/drug effects
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