Optimal control in HIV chemotherapy with termination viral load and latent reservoir

被引:6
作者
Olabode, Damilola [1 ]
Rong, Libin [2 ]
Wang, Xueying [1 ]
机构
[1] Washington State Univ, Dept Math & Stat, Pullman, WA 99164 USA
[2] Univ Florida, Dept Math, Gainesville, FL 32611 USA
基金
美国国家科学基金会;
关键词
HIV-1; latency; chemotherapy; ART/HAART; termination level; optimal control; INFECTION; DYNAMICS;
D O I
10.3934/mbe.2019030
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Although a number of cost-effective strategies have been proposed for the chemotherapy of HIV infection, the termination level of viral load and latent reservoir is barely considered. However, the viral load at the termination time is an important biomarker because suppressing viral load to below the detection limit is a major objective of current antiretroviral therapy. The pool size of latently infected cells at the termination time may also play a critical role in predicting a rapid viral rebound to the pretreatment level or post-treatment control. In this work, we formulate an optimal control problem by incorporating the termination level in terms of viral load, latently and productively infected T cells into an existing HIV model. The necessary condition for this optimal system is derived using the Pontryagin's maximum principle. Numerical analysis is carried out using Runge-Kutta 4 method for the forward-backward sweep. Our results suggest that introducing the termination viral load into the control provides a better strategy in HIV chemotherapy.
引用
收藏
页码:619 / 635
页数:17
相关论文
共 38 条
[1]   HIV dynamics: Modeling, data analysis, and optimal treatment protocols [J].
Adams, BM ;
Banks, HT ;
Davidian, M ;
Kwon, HD ;
Tran, HT ;
Wynne, SN ;
Rosenberg, ES .
JOURNAL OF COMPUTATIONAL AND APPLIED MATHEMATICS, 2005, 184 (01) :10-49
[2]   Modelling the Course of an HIV Infection: Insights from Ecology and Evolution [J].
Alizon, Samuel ;
Magnus, Carsten .
VIRUSES-BASEL, 2012, 4 (10) :1984-2013
[3]  
[Anonymous], 2011, CSH PERSPECT MED, DOI DOI 10.1101/cshperspect.a007096
[4]   HIV-1 Antiretroviral Drug Therapy [J].
Arts, Eric J. ;
Hazuda, Daria J. .
COLD SPRING HARBOR PERSPECTIVES IN MEDICINE, 2012, 2 (04)
[5]  
Asano E, 2008, MATH BIOSCI ENG, V5, P219
[6]   Adverse effects of reverse transcriptase inhibitors: mitochondrial toxicity as common pathway [J].
Brinkman, K ;
ter Hofstede, HJM ;
Burger, DM ;
Smeitinkt, JAM ;
Koopmans, PP .
AIDS, 1998, 12 (14) :1735-1744
[7]   HIV-1 infection and low steady state viral loads [J].
Callaway, DS ;
Perelson, AS .
BULLETIN OF MATHEMATICAL BIOLOGY, 2002, 64 (01) :29-64
[8]   Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy [J].
Chun, TW ;
Stuyver, L ;
Mizell, SB ;
Ehler, LA ;
Mican, JAM ;
Baseler, M ;
Lloyd, AL ;
Nowak, MA ;
Fauci, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (24) :13193-13197
[9]   Post-treatment control of HIV infection [J].
Conway, Jessica M. ;
Perelson, Alan S. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2015, 112 (17) :5467-5472
[10]  
Croicu AM, 2015, B MATH BIOL, V77, P2035, DOI 10.1007/s11538-015-0114-4