Models and estimation methods for clinical HIV-1 data

Clinical HIV-1 data include many individual factors, such as compliance to treatment, pharmacokinetics, variability in respect to viral dynamics, race, sex, income, etc., which might directly influence or be associated with clinical outcome. These factors need to be taken into account to achieve a better understanding of clinical outcome and mathematical models can provide a unifying framework to do so. The first objective of this paper is to demonstrate the development of comprehensive HIV-1 dynamics models that describe viral dynamics and also incorporate different factors influencing such dynamics. The second objective of this paper is to describe alternative estimation methods that can be applied to the analysis of data with such models. In particular, we consider: (i) simple but effective two-stage estimation methods, in which data from each patient are analyzed separately and summary statistics derived from the results, (ii) more complex nonlinear mixed effect models, used to pool all the patient data in a single analysis. Bayesian estimation methods are also considered, in particular: (iii) maximum posterior approximations, MAP, and (iv) Markov chain Monte Carlo, MCMC. Bayesian methods incorporate prior knowledge into the models, thus avoiding some of the model simplifications introduced when the data are analyzed using two-stage methods, or a nonlinear mixed effect framework. We demonstrate the development of the models and the different estimation methods using real AIDS clinical trial data involving patients receiving multiple drugs regimens.