Uncertainty quantification for the random HIV dynamical model driven by drug adherence.

ABSTRACT

In HIV drug therapy, the high variability of CD4+ T cells and viral loads brings uncertainty to the determination of treatment options and the ultimate treatment efficacy, which may be the result of poor drug adherence. We develop a dynamical HIV model coupled with pharmacokinetics, driven by drug adherence as a random variable, and systematically study the uncertainty quantification, aiming to construct the relationship between drug adherence and therapeutic effect. Using adaptive generalized polynomial chaos, stochastic solutions are approximated as polynomials of input random parameters. Numerical simulations show that results obtained by this method are in good agreement, compared with results obtained through Monte Carlo sampling, which helps to verify the accuracy of approximation. Based on these expansions, we calculate the time-dependent probability density functions of this system theoretically and numerically. To verify the applicability of this model, we fit clinical data of four HIV patients, and the goodness of fit results demonstrate that the proposed random model depicts the dynamics of HIV well. Sensitivity analyses based on the Sobol index indicate that the randomness of drug effect has the greatest impact on both CD4+ T cells and viral loads, compared to random initial values, which further highlights the significance of drug adherence. The proposed models and qualitative analysis results, along with monitoring CD4+ T cells counts and viral loads, evaluate the influence of drug adherence on HIV treatment, which helps to better interpret clinical data with fluctuations and makes several contributions to the design of individual-based optimal antiretroviral strategies.