AN AGE-STRUCTURED MODEL WITH IMMUNE RESPONSE OF HIV INFECTION: MODELING AND OPTIMAL CONTROL APPROACH

被引:10
作者
Kwon, Hee-Dae [1 ]
Lee, Jeehyun [2 ]
Yoon, Myoungho [3 ]
机构
[1] Inha Univ, Dept Math, Inchon 402751, South Korea
[2] Yonsei Univ, Dept Computat Sci & Engn, Seoul 120749, South Korea
[3] Yonsei Univ, Dept Math, Seoul 120749, South Korea
来源
DISCRETE AND CONTINUOUS DYNAMICAL SYSTEMS-SERIES B | 2014年 / 19卷 / 01期
基金
新加坡国家研究基金会;
关键词
HIV dynamics; age-structured model; immune response; optimal control; gradient method; MATHEMATICAL-MODEL; DYNAMICS; POPULATION; CHEMOTHERAPY; MUTATIONS;
D O I
10.3934/dcdsb.2014.19.153
中图分类号
O29 [应用数学];
学科分类号
070104 ;
摘要
This paper develops and analyzes an age-structured model of HIV infection with various compartments, including target cells, infected cells, viral loads and immune effector cells, to provide a better understanding of the interaction between HIV and the immune system. We show that the proposed model has one uninfected steady state and several infected steady states. We conduct a local stability analysis of these steady states by using a generalized Jacobian matrix method in conjunction with the Laplace transform. In addition, we consider various techniques and ideas from optimal control theory to derive optimal therapy protocols by using two types of dynamic treatment methods representing reverse transcriptase inhibitors and protease inhibitors. We derive the necessary conditions (an optimality system) for optimal control functions by considering the first variations of the Lagrangian. Further, we obtain optimal therapy protocols by solving a large optimality system of equations through the use of a difference scheme based on the Runge-Kutta method. The results of numerical simulations indicate that the optimal therapy protocols can facilitate long-term control of HIV through a strong immune response after the discontinuation of the therapy.
引用
收藏
页码:153 / 172
页数:20
相关论文
共 31 条
[21]   Diseases with chronic stage in a population with varying size [J].
Martcheva, M ;
Castillo-Chavez, C .
MATHEMATICAL BIOSCIENCES, 2003, 182 (01) :1-25
[22]   ZIDOVUDINE AND HIV - MATHEMATICAL-MODELS OF WITHIN-HOST POPULATION-DYNAMICS [J].
MCLEAN, AR ;
FROST, SDW .
REVIEWS IN MEDICAL VIROLOGY, 1995, 5 (03) :141-147
[23]  
Moore H, 2005, MATH BIOSCI ENG, V2, P363
[24]   An age-structured model of HIV infection that allows for variations in the production rate of viral particles and the death rate of productively infected cells [J].
Nelson, PW ;
Gilchrist, MA ;
Coombs, D ;
Hyman, JM ;
Perelson, AS .
MATHEMATICAL BIOSCIENCES AND ENGINEERING, 2004, 1 (02) :267-288
[25]   HIV-1-specific immune responses in subjects who temporarily contain virus replication after discontinuation of highly active antiretroviral therapy [J].
Ortiz, GM ;
Nixon, DF ;
Trkola, A ;
Binley, J ;
Jin, X ;
Bonhoeffer, S ;
Kuebler, PJ ;
Donahoe, SM ;
Demoitie, MA ;
Kakimoto, WM ;
Ketas, T ;
Clas, B ;
Heymann, JJ ;
Zhang, LQ ;
Cao, YZ ;
Hurley, A ;
Moore, JP ;
Ho, DD ;
Markowitz, M .
JOURNAL OF CLINICAL INVESTIGATION, 1999, 104 (06) :R13-R18
[26]   Mathematical analysis of HIV-1 dynamics in vivo [J].
Perelson, AS ;
Nelson, PW .
SIAM REVIEW, 1999, 41 (01) :3-44
[27]   NEVIRAPINE RESISTANCE MUTATIONS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SELECTED DURING THERAPY [J].
RICHMAN, DD ;
HAVLIR, D ;
CORBEIL, J ;
LOONEY, D ;
IGNACIO, C ;
SPECTOR, SA ;
SULLIVAN, J ;
CHEESEMAN, S ;
BARRINGER, K ;
PAULETTI, D ;
SHIH, CK ;
MYERS, M ;
GRIFFIN, J .
JOURNAL OF VIROLOGY, 1994, 68 (03) :1660-1666
[28]  
Shiri T, 2005, MATH BIOSCI ENG, V2, P811
[29]   Modeling plasma virus concentration during primary HIV infection [J].
Stafford, MA ;
Corey, L ;
Cao, YZ ;
Daar, ES ;
Ho, DD ;
Perelson, AS .
JOURNAL OF THEORETICAL BIOLOGY, 2000, 203 (03) :285-301
[30]   HOW MAY INFECTION-AGE-DEPENDENT INFECTIVITY AFFECT THE DYNAMICS OF HIV AIDS [J].
THIEME, HR ;
CASTILLOCHAVEZ, C .
SIAM JOURNAL ON APPLIED MATHEMATICS, 1993, 53 (05) :1447-1479