A two-loop robust controller for HIV infection models in the presence of parameter uncertainties

Abstract A two-loop robust nonlinear controller is proposed to deal with uncertain model parameters in HIV infection models, which are described by nonlinear differential equations of three state variables and antiretroviral drugs. The treatment goal is to suppress the concentration of infected CD4+ T cells to a target value using only the measurement of total CD4+ T cell concentration. The outer-loop controller is designed to achieve the treatment goal for the nominal HIV infection model, while a nonlinear disturbance observer (DOB) controller is employed in the inner-loop to compensate for parameter uncertainties. In the nonlinear DOB controller, a disturbance signal, equivalent to the parameter variation in terms of effect on the output, is canceled by its estimate. Numerical simulations verify that the proposed controller achieves robust performance for reducing the concentration of infected CD4+ T cells even in the presence of parameter uncertainties.

[1]  Ryan Zurakowski,et al.  Nonlinear observer output-feedback MPC treatment scheduling for HIV , 2011, Biomedical engineering online.

[2]  J. J. Henning,et al.  Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents, January 28, 2000 , 1998, HIV clinical trials.

[3]  Shuzhi Sam Ge,et al.  Nonlinear control of a dynamic model of HIV-1 , 2005, IEEE Transactions on Biomedical Engineering.

[4]  Hulin Wu,et al.  Hierarchical Bayesian Methods for Estimation of Parameters in a Longitudinal HIV Dynamic System , 2006, Biometrics.

[5]  Nam Hoon Jo,et al.  Input output linearization approach to state observer design for nonlinear system , 2000, IEEE Trans. Autom. Control..

[6]  Ryan Zurakowski,et al.  A model predictive control based scheduling method for HIV therapy. , 2006, Journal of theoretical biology.

[7]  Haihong Zhu,et al.  Parameter Identifiability and Estimation of HIV/AIDS Dynamic Models , 2008, Bulletin of mathematical biology.

[8]  A. Isidori Nonlinear Control Systems , 1985 .

[9]  Claude H. Moog,et al.  Clinical Tests of Therapeutical Failures Based on Mathematical Modeling of the HIV Infection , 2008, IEEE Transactions on Automatic Control.

[10]  Jin H. Seo,et al.  Local separation principle for non-linear systems , 2000 .

[11]  Carlos E. D'Attellis,et al.  Optimizing thymic recovery in HIV patients through multidrug therapies , 2013, Biomed. Signal Process. Control..

[12]  Hyungbo Shim,et al.  A system theoretic study on a treatment of AIDS patient by achieving long-term non-progressor , 2009, Autom..

[13]  Hyungbo Shim,et al.  Adding robustness to nominal output-feedback controllers for uncertain nonlinear systems: A nonlinear version of disturbance observer , 2008, Autom..

[14]  岩見真吾 Virus Dynamics:ウイルスダイナミクス , 2017 .

[15]  Alan S. Perelson,et al.  Mathematical Analysis of HIV-1 Dynamics in Vivo , 1999, SIAM Rev..

[16]  Michael J. Piovoso,et al.  HIV Model Parameter Estimates from Interruption Trial Data including Drug Efficacy and Reservoir Dynamics , 2012, PloS one.

[17]  Claude H. Moog,et al.  Control of the HIV infection and drug dosage , 2010, Biomed. Signal Process. Control..

[18]  J. K. Hedrick,et al.  The use of sliding modes to simplify the backstepping control method , 1997, Proceedings of the 1997 American Control Conference (Cat. No.97CH36041).

[19]  C. A. Desoer,et al.  Nonlinear Systems Analysis , 1978 .

[20]  I. Craig,et al.  Can HIV/AIDS be controlled? Applying control engineering concepts outside traditional fields , 2005, IEEE Control Systems.

[21]  Gabriele Pannocchia,et al.  A Model Predictive Control Strategy Toward Optimal Structured Treatment Interruptions in Anti-HIV Therapy , 2010, IEEE Transactions on Biomedical Engineering.

[22]  João Miranda Lemos,et al.  Nonlinear control of HIV-1 infection with a singular perturbation model , 2007, Biomed. Signal Process. Control..