Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy

HIV-1 infected patients are effectively treated with highly active anti-retroviral therapy (HAART). Whilst HAART is successful in keeping the disease at bay with average levels of viral load well below the detection threshold of standard clinical assays, it fails to completely eradicate the infectio...

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Autores: Sánchez Taltavull, Daniel, Vieiro Yanes, Arturo, Alarcón Cor, Tomás
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2016
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/193902
Acceso en línea:https://hdl.handle.net/2445/193902
Access Level:acceso abierto
Palabra clave:VIH (Virus)
Processos estocàstics
Sistemes estocàstics
Antiretrovirals
HIV (Viruses)
Stochastic processes
Stochastic systems
Antiretroviral agents
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spelling Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapySánchez Taltavull, DanielVieiro Yanes, ArturoAlarcón Cor, TomásVIH (Virus)Processos estocàsticsSistemes estocàsticsAntiretroviralsHIV (Viruses)Stochastic processesStochastic systemsAntiretroviral agentsHIV-1 infected patients are effectively treated with highly active anti-retroviral therapy (HAART). Whilst HAART is successful in keeping the disease at bay with average levels of viral load well below the detection threshold of standard clinical assays, it fails to completely eradicate the infection, which persists due to the emergence of a latent reservoir with a half-life time of years and is immune to HAART. This implies that life-long administration of HAART is, at the moment, necessary for HIV-1-infected patients, which is prone to drug resistance and cumulative side effects as well as imposing a considerable financial burden on developing countries, those more afflicted by HIV, and public health systems. The development of therapies which specifically aim at the removal of this latent reservoir has become a focus of much research. A proposal for such therapy consists of elevating the rate of activation of the latently infected cells: by transferring cells from the latently infected reservoir to the active infected compartment, more cells are exposed to the anti-retroviral drugs thus increasing their effectiveness. In this paper, we present a stochastic model of the dynamics of the HIV-1 infection and study the effect of the rate of latently infected cell activation on the average extinction time of the infection. By analysing the model by means of an asymptotic approximation using the semi-classical quasi steady state approximation (QSS), we ascertain that this therapy reduces the average life-time of the infection by many orders of magnitudes. We test the accuracy of our asymptotic results by means of direct simulation of the stochastic process using a hybrid multi-scale Monte Carlo scheme.Springer2023202320162023info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion28 p.application/pdfhttps://hdl.handle.net/2445/193902Articles publicats en revistes (Matemàtiques i Informàtica)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1007/s00285-016-0977-5Journal of Mathematical Biology, 2016, vol. 73, p. 919-946https://doi.org/10.1007/s00285-016-0977-5(c) Springer, 2016info:eu-repo/semantics/openAccessoai:recercat.cat:2445/1939022026-05-29T05:05:01Z
dc.title.none.fl_str_mv Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy
title Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy
spellingShingle Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy
Sánchez Taltavull, Daniel
VIH (Virus)
Processos estocàstics
Sistemes estocàstics
Antiretrovirals
HIV (Viruses)
Stochastic processes
Stochastic systems
Antiretroviral agents
title_short Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy
title_full Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy
title_fullStr Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy
title_full_unstemmed Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy
title_sort Stochastic modelling of the eradication of the HIV-1 infection by stimulation of latently infected cells in patients under highly active anti-retroviral therapy
dc.creator.none.fl_str_mv Sánchez Taltavull, Daniel
Vieiro Yanes, Arturo
Alarcón Cor, Tomás
author Sánchez Taltavull, Daniel
author_facet Sánchez Taltavull, Daniel
Vieiro Yanes, Arturo
Alarcón Cor, Tomás
author_role author
author2 Vieiro Yanes, Arturo
Alarcón Cor, Tomás
author2_role author
author
dc.subject.none.fl_str_mv VIH (Virus)
Processos estocàstics
Sistemes estocàstics
Antiretrovirals
HIV (Viruses)
Stochastic processes
Stochastic systems
Antiretroviral agents
topic VIH (Virus)
Processos estocàstics
Sistemes estocàstics
Antiretrovirals
HIV (Viruses)
Stochastic processes
Stochastic systems
Antiretroviral agents
description HIV-1 infected patients are effectively treated with highly active anti-retroviral therapy (HAART). Whilst HAART is successful in keeping the disease at bay with average levels of viral load well below the detection threshold of standard clinical assays, it fails to completely eradicate the infection, which persists due to the emergence of a latent reservoir with a half-life time of years and is immune to HAART. This implies that life-long administration of HAART is, at the moment, necessary for HIV-1-infected patients, which is prone to drug resistance and cumulative side effects as well as imposing a considerable financial burden on developing countries, those more afflicted by HIV, and public health systems. The development of therapies which specifically aim at the removal of this latent reservoir has become a focus of much research. A proposal for such therapy consists of elevating the rate of activation of the latently infected cells: by transferring cells from the latently infected reservoir to the active infected compartment, more cells are exposed to the anti-retroviral drugs thus increasing their effectiveness. In this paper, we present a stochastic model of the dynamics of the HIV-1 infection and study the effect of the rate of latently infected cell activation on the average extinction time of the infection. By analysing the model by means of an asymptotic approximation using the semi-classical quasi steady state approximation (QSS), we ascertain that this therapy reduces the average life-time of the infection by many orders of magnitudes. We test the accuracy of our asymptotic results by means of direct simulation of the stochastic process using a hybrid multi-scale Monte Carlo scheme.
publishDate 2016
dc.date.none.fl_str_mv 2016
2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/193902
url https://hdl.handle.net/2445/193902
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.1007/s00285-016-0977-5
Journal of Mathematical Biology, 2016, vol. 73, p. 919-946
https://doi.org/10.1007/s00285-016-0977-5
dc.rights.none.fl_str_mv (c) Springer, 2016
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Springer, 2016
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 28 p.
application/pdf
dc.publisher.none.fl_str_mv Springer
publisher.none.fl_str_mv Springer
dc.source.none.fl_str_mv Articles publicats en revistes (Matemàtiques i Informàtica)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,198674

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