Viral dynamics and anti-viral pharmacodynamics:: rethinking in vitro measures of drug potency

Most current assays used to quantitate the pharmacodynamic effect of anti-viral agents measure the net inhibitory effect of a drug on virus replication over several days in an in vitro cell culture. Such endpoint experiments give cumulative measures of inhibition that vary with the assay used and therefore provide suboptimal information on likely in vivo drug performance. We argue that instantaneous inhibition (proportion of cell infection prevented at a point in time) is a more robust pharmacodynamic measure, and propose techniques to estimate this quantity from endpoint data. Implications for the quantification of drug interactions are discussed.