Practical identifiability of HIV dynamics models

We study the practical identifiability of parameters, i.e., the accuracy of the estimation that can be hoped, in a model of HIV dynamics based on a system of non-linear Ordinary Differential Equations (ODE). This depends on the available information such as the schedule of the measurements, the observed components, and the measurement precision. The number of patients is another way to increase it by introducing an appropriate statistical "population" framework. The impact of each improvement of the experimental condition is not known in advance but it can be evaluated via the Fisher Information Matrix (FIM). If the non-linearity of the biological model, as well as the complex statistical framework makes computation of the FIM challenging, we show that the particular structure of these models enables to compute it as precisely as wanted. In the HIV model, measuring HIV viral load and total CD4+ count were not enough to achieve identifiability of all the parameters involved. However, we show that an appropriate statistical approach together with the availability of additional markers such as infected cells or activated cells should considerably improve the identifiability and thus the usefulness of dynamical models of HIV.