Optimizing thymic recovery in HIV patients through multidrug therapies

Autores
Costanza, Vicente; Rivadeneira Paz, Pablo Santiago; Biafore, Federico Leonardo; D'attellis, Carlos Enrique
Año de publicación
2012
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
A control-theoretic approach to the problem of designing `low-side-effects´ therapies for HIV patients based on highly active drugs is substantiated here. The evolution of side-effects during treatment is modelled by an extra differential equation coupled to the dynamics of virions, healthy T-cells, and infected ones.  The new equation reflects the dependence of collateral damages on the amount of each dose administered to the patient, and on the evolution of the viral load detected by periodical blood analyses.  The cost objective accounts for recommended bounds on healthy cells and virions, and also penalizes the appearance of collateral malignancies caused by the medication.  The problem is solved by a hybrid Dynamic Programming scheme that adhere to discrete-time observation and control actions, but maintaining the continuous-time setup for predicting states and side-effects.  The resulting optimal strategies employ less drugs than those prescribed by previous optimization studies, but maintaining high doses at the beginning and the end of each period of six months.  If an inverse discount rate is applied to favor early actions, and under a mild penalization of the final viral load, then the optimal doses are found to be high at the beginning and decrease afterwards, causing a desirable stabilization of the main variables.
Fil: Costanza, Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina
Fil: Rivadeneira Paz, Pablo Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina
Fil: Biafore, Federico Leonardo. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: D'attellis, Carlos Enrique. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Universidad Favaloro; Argentina
Materia
Antiretroviral Drugs
Optimal Control
Nonlinear Dynamics
Dynamic Programming
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/10903
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/10903
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Optimizing thymic recovery in HIV patients through multidrug therapiesCostanza, VicenteRivadeneira Paz, Pablo SantiagoBiafore, Federico LeonardoD'attellis, Carlos EnriqueAntiretroviral DrugsOptimal ControlNonlinear DynamicsDynamic Programminghttps://purl.org/becyt/ford/2.6https://purl.org/becyt/ford/2A control-theoretic approach to the problem of designing `low-side-effects´ therapies for HIV patients based on highly active drugs is substantiated here. The evolution of side-effects during treatment is modelled by an extra differential equation coupled to the dynamics of virions, healthy T-cells, and infected ones.  The new equation reflects the dependence of collateral damages on the amount of each dose administered to the patient, and on the evolution of the viral load detected by periodical blood analyses.  The cost objective accounts for recommended bounds on healthy cells and virions, and also penalizes the appearance of collateral malignancies caused by the medication.  The problem is solved by a hybrid Dynamic Programming scheme that adhere to discrete-time observation and control actions, but maintaining the continuous-time setup for predicting states and side-effects.  The resulting optimal strategies employ less drugs than those prescribed by previous optimization studies, but maintaining high doses at the beginning and the end of each period of six months.  If an inverse discount rate is applied to favor early actions, and under a mild penalization of the final viral load, then the optimal doses are found to be high at the beginning and decrease afterwards, causing a desirable stabilization of the main variables.Fil: Costanza, Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); ArgentinaFil: Rivadeneira Paz, Pablo Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); ArgentinaFil: Biafore, Federico Leonardo. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: D'attellis, Carlos Enrique. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Universidad Favaloro; ArgentinaElsevier2012-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/10903Costanza, Vicente; Rivadeneira Paz, Pablo Santiago; Biafore, Federico Leonardo; D'attellis, Carlos Enrique; Optimizing thymic recovery in HIV patients through multidrug therapies; Elsevier; Biomedical Signal Processing And Control; 8; 1; 5-2012; 90-971746-8094enginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.bspc.2012.06.002info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1746809412000705info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:45:01Zoai:ri.conicet.gov.ar:11336/10903instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:45:01.951CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Optimizing thymic recovery in HIV patients through multidrug therapies
title Optimizing thymic recovery in HIV patients through multidrug therapies
spellingShingle Optimizing thymic recovery in HIV patients through multidrug therapies
Costanza, Vicente
Antiretroviral Drugs
Optimal Control
Nonlinear Dynamics
Dynamic Programming
title_short Optimizing thymic recovery in HIV patients through multidrug therapies
title_full Optimizing thymic recovery in HIV patients through multidrug therapies
title_fullStr Optimizing thymic recovery in HIV patients through multidrug therapies
title_full_unstemmed Optimizing thymic recovery in HIV patients through multidrug therapies
title_sort Optimizing thymic recovery in HIV patients through multidrug therapies
dc.creator.none.fl_str_mv Costanza, Vicente
Rivadeneira Paz, Pablo Santiago
Biafore, Federico Leonardo
D'attellis, Carlos Enrique
author Costanza, Vicente
author_facet Costanza, Vicente
Rivadeneira Paz, Pablo Santiago
Biafore, Federico Leonardo
D'attellis, Carlos Enrique
author_role author
author2 Rivadeneira Paz, Pablo Santiago
Biafore, Federico Leonardo
D'attellis, Carlos Enrique
author2_role author
author
author
dc.subject.none.fl_str_mv Antiretroviral Drugs
Optimal Control
Nonlinear Dynamics
Dynamic Programming
topic Antiretroviral Drugs
Optimal Control
Nonlinear Dynamics
Dynamic Programming
purl_subject.fl_str_mv https://purl.org/becyt/ford/2.6
https://purl.org/becyt/ford/2
dc.description.none.fl_txt_mv A control-theoretic approach to the problem of designing `low-side-effects´ therapies for HIV patients based on highly active drugs is substantiated here. The evolution of side-effects during treatment is modelled by an extra differential equation coupled to the dynamics of virions, healthy T-cells, and infected ones.  The new equation reflects the dependence of collateral damages on the amount of each dose administered to the patient, and on the evolution of the viral load detected by periodical blood analyses.  The cost objective accounts for recommended bounds on healthy cells and virions, and also penalizes the appearance of collateral malignancies caused by the medication.  The problem is solved by a hybrid Dynamic Programming scheme that adhere to discrete-time observation and control actions, but maintaining the continuous-time setup for predicting states and side-effects.  The resulting optimal strategies employ less drugs than those prescribed by previous optimization studies, but maintaining high doses at the beginning and the end of each period of six months.  If an inverse discount rate is applied to favor early actions, and under a mild penalization of the final viral load, then the optimal doses are found to be high at the beginning and decrease afterwards, causing a desirable stabilization of the main variables.
Fil: Costanza, Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina
Fil: Rivadeneira Paz, Pablo Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe. Instituto de Desarrollo Tecnológico Para la Industria Química (i); Argentina
Fil: Biafore, Federico Leonardo. Universidad Favaloro; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: D'attellis, Carlos Enrique. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Universidad Favaloro; Argentina
description A control-theoretic approach to the problem of designing `low-side-effects´ therapies for HIV patients based on highly active drugs is substantiated here. The evolution of side-effects during treatment is modelled by an extra differential equation coupled to the dynamics of virions, healthy T-cells, and infected ones.  The new equation reflects the dependence of collateral damages on the amount of each dose administered to the patient, and on the evolution of the viral load detected by periodical blood analyses.  The cost objective accounts for recommended bounds on healthy cells and virions, and also penalizes the appearance of collateral malignancies caused by the medication.  The problem is solved by a hybrid Dynamic Programming scheme that adhere to discrete-time observation and control actions, but maintaining the continuous-time setup for predicting states and side-effects.  The resulting optimal strategies employ less drugs than those prescribed by previous optimization studies, but maintaining high doses at the beginning and the end of each period of six months.  If an inverse discount rate is applied to favor early actions, and under a mild penalization of the final viral load, then the optimal doses are found to be high at the beginning and decrease afterwards, causing a desirable stabilization of the main variables.
publishDate 2012
dc.date.none.fl_str_mv 2012-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/10903
Costanza, Vicente; Rivadeneira Paz, Pablo Santiago; Biafore, Federico Leonardo; D'attellis, Carlos Enrique; Optimizing thymic recovery in HIV patients through multidrug therapies; Elsevier; Biomedical Signal Processing And Control; 8; 1; 5-2012; 90-97
1746-8094
url http://hdl.handle.net/11336/10903
identifier_str_mv Costanza, Vicente; Rivadeneira Paz, Pablo Santiago; Biafore, Federico Leonardo; D'attellis, Carlos Enrique; Optimizing thymic recovery in HIV patients through multidrug therapies; Elsevier; Biomedical Signal Processing And Control; 8; 1; 5-2012; 90-97
1746-8094
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bspc.2012.06.002
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1746809412000705
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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