Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against feline immunodeficiency virus in feline peripheral blood mononuclear cells
2014
Schwartz, Anita M. | McCrackin, Mary Ann | Schinazi, Raymond F. | Hill, Peter B. | Vahlenkamp, Thomas W. | Tompkins, Mary B. | Hartmann, Katrin
Objective-To compare cytotoxic effects and antiviral efficacy of 9 nucleoside reverse transcriptase inhibitors (NRTIs) against FIV in feline peripheral blood mononuclear cells. Sample-Peripheral blood mononuclear cells obtained from 3 specific pathogen-free cats. Procedures-3 of the 9 NRTIs had not been previously assessed in feline cell lines. Cytotoxic effects were determined by colorimetric quantification of a formazan product resulting from bioreduction of a tetrazolium reagent by viable peripheral blood mononuclear cells; uninfected cells from 1 cat were used in these assays. Cells from all 3 cats were infected with a pathogenic clone of FIV, and in vitro antiviral efficacy of each NRTI was assessed with an FIV p24 antigen capture ELISA. Results-Cytotoxic effects in feline peripheral blood mononuclear cells were observed only at concentrations > 10 μM for all 9 NRTIs. Comparison of the cytotoxic effect at the highest concentration investigated (500μM) revealed that didanosine and amdoxovir were significantly less toxic than abacavir. All drugs induced a dose-dependent reduction of FIV replication. At the highest concentration investigated (10μM), there was no significant difference in antiviral efficacy among the test compounds. Conclusions and Clinical Relevance-The evaluated NRTIs had low cytotoxicity against feline peripheral blood mononuclear cells and appeared to be safe options for further in vivo evaluation for the treatment of FIV-infected cats. There was no evidence suggesting that the newly evaluated compounds would be superior to the existing NRTIs for reducing FIV burden of infected cats.
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