Antiviral efficacy of nine nucleoside reverse transcriptase inhibitors against feline immunodeficiency virus in feline peripheral blood mononuclear cells

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 (500 μM) 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 (10 μM), 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.

Anita M. Schwartz, Mary Ann McCrackin, Raymond F. Schinazi, Peter B. Hill, Thomas W. Vahlenkamp, Mary B. Tompkins, Katrin Hartmann