Antiviral activity of dolutegravir against site-directed mutants of HIV-1 and HIV-2 integrase in the single-cycle assay. (A) EC50 values for wild-type (WT) HIV-2ROD9 and HIV-2ROD9 integrase mutants generated in the full-length pROD9 molecular clone. Shaded bars indicate strains that are significantly different from wild-type (p < 0.05, ANOVA of log10-transformed EC50 values with Tukey’s post test; Prism v6.0). The number of independent determinations (n) for each strain is shown below the x-axis. (B) and (C) Representative dose-response profiles for WT, E92Q + N155H, G140S + Q148R and T97A + Y143C HIV-2ROD9. Data are the means of three independent cultures at each dose of dolutegravir (DTG). Curve fits were generated as described in Figure 1A. (D) Comparative analysis of equivalent site-directed mutants of HIV-1 and HIV-2 integrase. Each point is the result of a single dose-response assay performed as described in Figure 1A. Horizontal bars indicate the mean EC50 values for each strain. Red arrows and text indicate fold increases in the mean EC50 values for HIV-2 relative to HIV-1. ANOVA results for these data are described in the main text. In all panels, error bars represent standard deviations.