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

The purpose of the study reported here was to compare the antiviral efficacy against feline immunodeficiency virus (FIV) and cytotoxicity in feline peripheral blood mononuclear (PBM) cells of 9 nucleoside reverse transcriptase inhibitors (NRTIs), three of which had not been evaluated against FIV in feline cells before. PBM cells were isolated from the blood of three specific pathogen-free (SPF) cats. The cytotoxic effects of the test compounds were determined by colorimetric quantification of a formazan product resulting from bioreduction of a tetrazolium reagent by viable PBM cells. Each compound was tested in 12 concentrations ranging from 0.001 to 500 M. Uninfected cells from one SPF cat were used in these assays. PBM cells (from all three SPF cats) were infected with the molecular clone FIV pPPR and the antiviral efficacy of the test compounds was assessed using a FIV p24 antigen capture enzyme-linked immunosorbent assay. Each compound was tested in 5 concentrations ranging from 0.1 to 10 M. Cytotoxic effects in feline PBM cells were observed only at concentrations over 10 M for all 9 NRTIs. Comparison of the cytotoxic effect at the highest concentration investigated (500 M) revealed that didanosine and amdoxovir were significantly less toxic than abacavir. As no cytotoxicity was noted up to a concentration of 10 M, this was set as the highest concentration for the second part of this study investigating the anti-FIV efficacy of the test compounds. All drugs induced a dose-dependent reduction of FIV replication. When compared at the highest concentration investigated, there was no significant difference in the antiviral efficacy among the test compounds. The EC50 could not be determined as none of the test compounds achieved 50% viral inhibition. The evaluated NRTIs had low cytotoxicity against feline PBM cells and appear 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 the FIV burden of infected cats.