Optimal Controls of the Highly Active Antiretroviral Therapy

In this paper, we study generic properties of the optimal, in a certain sense, highly active antiretroviral therapy (or HAART). To address this problem, we consider a control model based on the 3-dimensional Nowak–May within-host HIV dynamics model. Taking into consideration that precise forms of fu...

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Main Authors: Ellina V. Grigorieva, Evgenii N. Khailov, Andrei Korobeinikov
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Abstract and Applied Analysis
Online Access:http://dx.doi.org/10.1155/2020/8107106
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author Ellina V. Grigorieva
Evgenii N. Khailov
Andrei Korobeinikov
author_facet Ellina V. Grigorieva
Evgenii N. Khailov
Andrei Korobeinikov
author_sort Ellina V. Grigorieva
collection DOAJ
description In this paper, we study generic properties of the optimal, in a certain sense, highly active antiretroviral therapy (or HAART). To address this problem, we consider a control model based on the 3-dimensional Nowak–May within-host HIV dynamics model. Taking into consideration that precise forms of functional responses are usually unknown, we introduce into this model a nonlinear incidence rate of a rather general form given by an unspecified function of the susceptible cells and free virus particles. We also add a term responsible to the loss of free virions due to infection of the target cells. To mirror the idea of highly active anti-HIV therapy, in this model we assume six controls that can act simultaneously. These six controls affecting different stage of virus life cycle comprise all controls possible for this model and account for all feasible actions of the existing anti-HIV drugs. With this control model, we consider an optimal control problem of minimizing the infection level at the end of a given time interval. Using an analytical mathematical technique, we prove that the optimal controls are bang-bang, find accurate estimates for the maximal possible number of switchings of these controls and establish qualitative types of the optimal controls as well as mutual relationships between them. Having the estimate for the number of switchings found, we can reduce the two-point boundary value problem for Pontryagin Maximum Principle to a considerably simpler problem of the finite-dimensional optimization, which can be solved numerically. Despite this possibility, the obtained theoretical results are illustrated by numerical calculations using BOCOP–2.0.5 software package, and the corresponding conclusions are made.
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spelling doaj-art-08ada90a02714b5fbd6a80f976d796542025-08-20T03:55:32ZengWileyAbstract and Applied Analysis1085-33751687-04092020-01-01202010.1155/2020/81071068107106Optimal Controls of the Highly Active Antiretroviral TherapyEllina V. Grigorieva0Evgenii N. Khailov1Andrei Korobeinikov2Department of Mathematics and Computer Sciences, Texas Woman’s University, Denton, TX 76204, USADepartment of Computational Mathematics and Cybernetics, Moscow State Lomonosov University, Moscow 119992, RussiaCentre de Recerca Matemática, Campus de Bellaterra, Edifici C, 08193 Bellaterra, Barcelona, SpainIn this paper, we study generic properties of the optimal, in a certain sense, highly active antiretroviral therapy (or HAART). To address this problem, we consider a control model based on the 3-dimensional Nowak–May within-host HIV dynamics model. Taking into consideration that precise forms of functional responses are usually unknown, we introduce into this model a nonlinear incidence rate of a rather general form given by an unspecified function of the susceptible cells and free virus particles. We also add a term responsible to the loss of free virions due to infection of the target cells. To mirror the idea of highly active anti-HIV therapy, in this model we assume six controls that can act simultaneously. These six controls affecting different stage of virus life cycle comprise all controls possible for this model and account for all feasible actions of the existing anti-HIV drugs. With this control model, we consider an optimal control problem of minimizing the infection level at the end of a given time interval. Using an analytical mathematical technique, we prove that the optimal controls are bang-bang, find accurate estimates for the maximal possible number of switchings of these controls and establish qualitative types of the optimal controls as well as mutual relationships between them. Having the estimate for the number of switchings found, we can reduce the two-point boundary value problem for Pontryagin Maximum Principle to a considerably simpler problem of the finite-dimensional optimization, which can be solved numerically. Despite this possibility, the obtained theoretical results are illustrated by numerical calculations using BOCOP–2.0.5 software package, and the corresponding conclusions are made.http://dx.doi.org/10.1155/2020/8107106
spellingShingle Ellina V. Grigorieva
Evgenii N. Khailov
Andrei Korobeinikov
Optimal Controls of the Highly Active Antiretroviral Therapy
Abstract and Applied Analysis
title Optimal Controls of the Highly Active Antiretroviral Therapy
title_full Optimal Controls of the Highly Active Antiretroviral Therapy
title_fullStr Optimal Controls of the Highly Active Antiretroviral Therapy
title_full_unstemmed Optimal Controls of the Highly Active Antiretroviral Therapy
title_short Optimal Controls of the Highly Active Antiretroviral Therapy
title_sort optimal controls of the highly active antiretroviral therapy
url http://dx.doi.org/10.1155/2020/8107106
work_keys_str_mv AT ellinavgrigorieva optimalcontrolsofthehighlyactiveantiretroviraltherapy
AT evgeniinkhailov optimalcontrolsofthehighlyactiveantiretroviraltherapy
AT andreikorobeinikov optimalcontrolsofthehighlyactiveantiretroviraltherapy