FIG. 4.

Three-dimensional residual plots comparing experimental (observed) and predicted levels of HBV replication for antiviral combination data. The results of each antiviral combination experiment were analyzed by graphing the difference between observed antiviral effects and effects predicted from the single drug controls based on the Loewe additivity model (see Materials and Methods). The antiviral effect is presented in the z plane as a fraction of total viral replication (derived from untreated controls). The concentration of adefovir (in micromoles) is indicated on the y axes, and concentrations of the second drugs (in micromoles) are graphed on the x axes. Points that fall above the additive zero-interaction plane (z = 0) can be considered synergistic, since the observed antiviral effect was greater than predicted; conversely, points falling below the zero-interaction plane can be considered antagonistic. Each graph presents the results of one triplicate experiment where adefovir was assayed in combination with lamivudine (A), entecavir (B), FTC (C), L-dT (D), or tenofovir (E).