Applications of Influenza Viral Kinetic Modeling in Drug Development

Purpose of Review: Seasonal influenza epidemics continue to cause significant morbidity and mortality, especially in high-risk subpopulations. The rise of drug-resistant influenza strains and high rates of vaccine mismatches drives the search for new safe and effective antiviral drugs. The purpose of this review was to summarize how mathematical models―viral kinetic models, in particular―have advanced our understanding of influenza biology and antiviral pharmacology and to explore how these models may be further developed in the future. Recent Findings: Viral kinetic models that use a population approach have been helpful in elucidating the major sources of intra- and inter-individual variability. Thus, these models can help explain why some influenza patients become much sicker than others. Linking viral kinetic models to pharmacokinetic/pharmacodynamic models has enabled quantification of drug effects based on their mechanism of action and in silico evaluation of the efficacy of drug combinations. Viral kinetic models have also been applied to optimizing the design of clinical trials. Future directions for viral kinetic models include coupling to epidemiological models to assess the effectiveness of various public health treatment strategies. These models can also inform health economic decision-making. Summary: Since the 1970s, the field of viral kinetic modeling of influenza has made great advances in informing our knowledge of this infectious disease. This tool is being coupled to other types of modeling approaches and will continue to be a critical weapon in our infectious disease armamentarium.