ETD Collection

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    Investigating viral parameter dependence on cell and viral life cycle assumptions
    (2007-03-01T12:39:05Z) Pretorius, Carel Diederik
    This dissertation reviews population dynamic type models of viral infection and introduces some new models to describe strain competition and the infected cell lifecycle. Laboratory data from a recent clinical trial, tracking drug resistant virus in patients given a short course of monotherapy is comprehensively analysed, paying particular attention to reproducibility. A Bayesian framework is introduced, which facilitates the inference of model parameters from the clinical data. It appears that the rapid emergence of resistance is a challenge to popular unstructured models of viral infection, and this challenge is partly addressed. In particular, it appears that minimal ordinary differential equations, with their implicit exponential lifetime (constant hazard) distributions in all compartments, lack the short transient timescales observed clinically. Directions for future work, both in terms of obtaining more informative data, and developing more systematic approaches to model building, are identified.