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Low-level HIV-1 replication and the dynamics of the resting CD4(+ )T cell reservoir for HIV-1 in the setting of HAART

BACKGROUND: In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4(+ )T cells is a source of cont...

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Autores principales: Sedaghat, Ahmad R, Siliciano, Robert F, Wilke, Claus O
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254415/
https://www.ncbi.nlm.nih.gov/pubmed/18171475
http://dx.doi.org/10.1186/1471-2334-8-2
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author Sedaghat, Ahmad R
Siliciano, Robert F
Wilke, Claus O
author_facet Sedaghat, Ahmad R
Siliciano, Robert F
Wilke, Claus O
author_sort Sedaghat, Ahmad R
collection PubMed
description BACKGROUND: In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4(+ )T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. METHODS: Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. RESULTS: By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. CONCLUSION: The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.
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spelling pubmed-22544152008-02-26 Low-level HIV-1 replication and the dynamics of the resting CD4(+ )T cell reservoir for HIV-1 in the setting of HAART Sedaghat, Ahmad R Siliciano, Robert F Wilke, Claus O BMC Infect Dis Research Article BACKGROUND: In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-1 (HIV-1) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4(+ )T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-1 infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. METHODS: Here we use a mathematical model of T cell dynamics in the setting of HIV-1 infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. RESULTS: By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. CONCLUSION: The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-1 infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir. BioMed Central 2008-01-02 /pmc/articles/PMC2254415/ /pubmed/18171475 http://dx.doi.org/10.1186/1471-2334-8-2 Text en Copyright © 2008 Sedaghat et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Sedaghat, Ahmad R
Siliciano, Robert F
Wilke, Claus O
Low-level HIV-1 replication and the dynamics of the resting CD4(+ )T cell reservoir for HIV-1 in the setting of HAART
title Low-level HIV-1 replication and the dynamics of the resting CD4(+ )T cell reservoir for HIV-1 in the setting of HAART
title_full Low-level HIV-1 replication and the dynamics of the resting CD4(+ )T cell reservoir for HIV-1 in the setting of HAART
title_fullStr Low-level HIV-1 replication and the dynamics of the resting CD4(+ )T cell reservoir for HIV-1 in the setting of HAART
title_full_unstemmed Low-level HIV-1 replication and the dynamics of the resting CD4(+ )T cell reservoir for HIV-1 in the setting of HAART
title_short Low-level HIV-1 replication and the dynamics of the resting CD4(+ )T cell reservoir for HIV-1 in the setting of HAART
title_sort low-level hiv-1 replication and the dynamics of the resting cd4(+ )t cell reservoir for hiv-1 in the setting of haart
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2254415/
https://www.ncbi.nlm.nih.gov/pubmed/18171475
http://dx.doi.org/10.1186/1471-2334-8-2
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