Optimal Control of HIV-Virus Dynamics

In this paper we consider a mathematical model of HIV-virus dynamics and propose an efficient control strategy to keep the number of HIV virons under a pre-specified level and to reduce the total amount of medications that patients receive. The model considered is a nonlinear third-order model. The third-order model describes dynamics of three most dominant variables: number of healthy white blood cells (T-cells), number of infected T-cells, and number of virus particles. There are two control variables in this model corresponding to two categories of antiviral drugs: reverse transcriptase inhibitors (RTI) and protease inhibitors (PI). The proposed strategy is based on linearization of the nonlinear model at the equilibrium point (steady state). The corresponding controller has two components: the first one that keeps the system state variables at the desired equilibrium (set-point controller) and the second-one that reduces in an optimal way deviations of the system state variables from their desired equilibrium values. The second controller is based on minimization of the square of the error between the actual and desired (equilibrium) values for the linearized system (linear-quadratic optimal controller). The obtained control strategy recommends to HIV researchers and experimentalists that the constant dosages of drugs have to be administrated at all times (set point controller, open-loop controller) and that the variable dosages of drugs have to be administrated on a daily basis (closed-loop controller, feedback controller).

[1]  Xiaohua Xia,et al.  Estimation of HIV/AIDS parameters , 2003, Autom..

[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]  E D Sontag,et al.  Some new directions in control theory inspired by systems biology. , 2004, Systems biology.

[4]  Karl Johan Åström,et al.  PID Controllers: Theory, Design, and Tuning , 1995 .

[5]  Douglas Richman,et al.  Viral Dynamics of HIV: Implications for Drug Development and Therapeutic Strategies , 1996, Annals of Internal Medicine.

[6]  Xiaohua Xia,et al.  Introducing HIV/AIDS education into the electrical engineering curriculum at the University of Pretoria , 2004, IEEE Transactions on Education.

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

[8]  Henry J. Kaiser,et al.  Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. Department of Health and Human Services and Henry J. Kaiser Family Foundation. , 1998, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[9]  A. Perelson,et al.  HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time , 1996, Science.

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

[11]  A Kremling,et al.  Systems biology--an engineering perspective. , 2007, Journal of biotechnology.

[12]  Bernard Friedland,et al.  Advanced Control System Design , 1996 .

[13]  Guanrong Chen,et al.  Feedback control of a biodynamical model of HIV-1 , 2001, IEEE Transactions on Biomedical Engineering.

[14]  Eduardo D. Sontag,et al.  Molecular Systems Biology and Control , 2005, Eur. J. Control.

[15]  F. D. Souza Modeling the dynamics of HIV-1 and CD4 and CD8 lymphocytes , 1999 .

[16]  F M de Souza Modeling the dynamics of HIV-1 and CD4 and CD8 lymphocytes. , 1999, IEEE engineering in medicine and biology magazine : the quarterly magazine of the Engineering in Medicine & Biology Society.

[17]  M. Nowak,et al.  Virus dynamics: Mathematical principles of immunology and virology , 2001 .

[18]  Panos Y. Papalambros Systems and Design , 2010 .

[19]  Xiaohua Xia,et al.  When to initiate HIV therapy: a control theoretic approach , 2003, IEEE Transactions on Biomedical Engineering.

[20]  Chung Choo Chung,et al.  Optimized structured treatment interruption for HIV therapy and its performance analysis on controllability , 2006, 2004 43rd IEEE Conference on Decision and Control (CDC) (IEEE Cat. No.04CH37601).

[21]  R. Culshaw,et al.  REVIEW OF HIV MODELS: THE ROLE OF THE NATURAL IMMUNE RESPONSE AND IMPLICATIONS FOR TREATMENT , 2004 .

[22]  D. Fuchs,et al.  Oxidative Stress and Apoptosis in HIV Infection , 1996, Science.

[23]  A. Perelson,et al.  Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection , 1995, Nature.

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

[25]  Harvey Thomas Banks,et al.  A state‐dependent Riccati equation‐based estimator approach for HIV feedback control , 2006 .