In vitro antiviral activity of currently available drugs against primary HIV isolates with high growth capability

Abstract Background It has been considered that virologic failure can occur with drug-resistance mutations in the HIV genome. In the present study, we assessed the influence of growth capability of HIV strains to drug response resulting in virologic failure. Phytohemagglutinin-activated peripheral blood mononuclear cells (1.5×106 cells) were infected with HIV strains (106 copies/mL) in vitro. The culture was carried out in different concentrations (0.001 to 20 µM) of twelve commercially available antiretroviral synthetic compounds (five nucleoside/nucleotide reverse transcriptase inhibitors, one non-nucleoside reverse transcriptase inhibitor, four integrase inhibitors, and two protease inhibitors), and HIV production was assessed using HIV-RNA copies in culture. The 90% inhibitory concentration (IC90) was used as an indicator of antiviral activity. Result Tenofovir (TFV) showed an IC90 of 2.05 ± 0.71 µM above the maximum concentration that a drug achieves (Cmax) after dosing of Tenofovir disoproxil fumarate (prodrug of TFV) against a strain with high growth capability without any drug resistance-related mutations. Lamivudine, emtricitabine, and efavirenz had IC90 values close to the Cmin-Cmax range against the strain. Atazanavir, tenofovir alafenamide, zidovudine, and dolutegravir had the lowest IC90 values of 0.03, 0.40, 0.50 and 0.50 nM, respectively, against the strain. Conclusion These results suggest that high growth capability of the strains influences virologic failure.