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Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients

BACKGROUND: A persistent immune activation is observed in gut during HIV-1 infection, which is not completely reversed by a combined antiretroviral therapy (cART). The impact of the time of cART initiation may highly influence the size of the viral reservoir and the ratio of CD4(+)/CD8(+) T cells in...

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Autores principales: Depincé-Berger, Anne-Emmanuelle, Vergnon-Miszczycha, Delphine, Girard, Alexandre, Frésard, Anne, Botelho-Nevers, Elisabeth, Lambert, Claude, Del Tedesco, Emilie, Genin, Christian, Pozzetto, Bruno, Lucht, Frédéric, Roblin, Xavier, Bourlet, Thomas, Paul, Stéphane
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929778/
https://www.ncbi.nlm.nih.gov/pubmed/27363286
http://dx.doi.org/10.1186/s12977-016-0278-5
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author Depincé-Berger, Anne-Emmanuelle
Vergnon-Miszczycha, Delphine
Girard, Alexandre
Frésard, Anne
Botelho-Nevers, Elisabeth
Lambert, Claude
Del Tedesco, Emilie
Genin, Christian
Pozzetto, Bruno
Lucht, Frédéric
Roblin, Xavier
Bourlet, Thomas
Paul, Stéphane
author_facet Depincé-Berger, Anne-Emmanuelle
Vergnon-Miszczycha, Delphine
Girard, Alexandre
Frésard, Anne
Botelho-Nevers, Elisabeth
Lambert, Claude
Del Tedesco, Emilie
Genin, Christian
Pozzetto, Bruno
Lucht, Frédéric
Roblin, Xavier
Bourlet, Thomas
Paul, Stéphane
author_sort Depincé-Berger, Anne-Emmanuelle
collection PubMed
description BACKGROUND: A persistent immune activation is observed in gut during HIV-1 infection, which is not completely reversed by a combined antiretroviral therapy (cART). The impact of the time of cART initiation may highly influence the size of the viral reservoir and the ratio of CD4(+)/CD8(+) T cells in the gut. In this study, we analyzed the characteristics of HIV rectal reservoir of long-term treated patients, regarding their blood CD4(+) T cells count at the time of cART initiation. RESULTS: Twenty-four consenting men were enrolled: 9 exhibiting a CD4(+) T cells count >350/mm(3) (“high-level CD4 group”) and 15 < 350/mm(3) (“low-level CD4 group”) in blood, at the start of cART. An immunophenotypical analysis of T and B cells subpopulations was performed in blood and rectal biopsies. HIV cell-associated DNA loads and qualitative intra-cellular RNA were determined in both compartments. The ratio of CD4(+)/CD8(+) T cells was significantly decreased in the blood but not in the rectum of the “low-level CD4 group” of patients. The alteration in β7(+) CD4(+) T cells homing was higher in this group and was correlated to a low ratio of CD4(+)/CD8(+) T cells in blood. An initiation of cART in men exhibiting a low-level CD4 count was also associated with an alteration of B cells maturation. HIV blood and gut DNA reservoirs were significantly lower in the “high-level CD4 group” of men. A high HIV DNA level was associated to a detectable intracellular HIV RNA in rectum. CONCLUSIONS: An early initiation of cART could significantly preserve gut immunity and limit the viral reservoir constitution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-016-0278-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-49297782016-07-02 Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients Depincé-Berger, Anne-Emmanuelle Vergnon-Miszczycha, Delphine Girard, Alexandre Frésard, Anne Botelho-Nevers, Elisabeth Lambert, Claude Del Tedesco, Emilie Genin, Christian Pozzetto, Bruno Lucht, Frédéric Roblin, Xavier Bourlet, Thomas Paul, Stéphane Retrovirology Research BACKGROUND: A persistent immune activation is observed in gut during HIV-1 infection, which is not completely reversed by a combined antiretroviral therapy (cART). The impact of the time of cART initiation may highly influence the size of the viral reservoir and the ratio of CD4(+)/CD8(+) T cells in the gut. In this study, we analyzed the characteristics of HIV rectal reservoir of long-term treated patients, regarding their blood CD4(+) T cells count at the time of cART initiation. RESULTS: Twenty-four consenting men were enrolled: 9 exhibiting a CD4(+) T cells count >350/mm(3) (“high-level CD4 group”) and 15 < 350/mm(3) (“low-level CD4 group”) in blood, at the start of cART. An immunophenotypical analysis of T and B cells subpopulations was performed in blood and rectal biopsies. HIV cell-associated DNA loads and qualitative intra-cellular RNA were determined in both compartments. The ratio of CD4(+)/CD8(+) T cells was significantly decreased in the blood but not in the rectum of the “low-level CD4 group” of patients. The alteration in β7(+) CD4(+) T cells homing was higher in this group and was correlated to a low ratio of CD4(+)/CD8(+) T cells in blood. An initiation of cART in men exhibiting a low-level CD4 count was also associated with an alteration of B cells maturation. HIV blood and gut DNA reservoirs were significantly lower in the “high-level CD4 group” of men. A high HIV DNA level was associated to a detectable intracellular HIV RNA in rectum. CONCLUSIONS: An early initiation of cART could significantly preserve gut immunity and limit the viral reservoir constitution. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-016-0278-5) contains supplementary material, which is available to authorized users. BioMed Central 2016-06-30 /pmc/articles/PMC4929778/ /pubmed/27363286 http://dx.doi.org/10.1186/s12977-016-0278-5 Text en © The Author(s) 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Depincé-Berger, Anne-Emmanuelle
Vergnon-Miszczycha, Delphine
Girard, Alexandre
Frésard, Anne
Botelho-Nevers, Elisabeth
Lambert, Claude
Del Tedesco, Emilie
Genin, Christian
Pozzetto, Bruno
Lucht, Frédéric
Roblin, Xavier
Bourlet, Thomas
Paul, Stéphane
Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients
title Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients
title_full Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients
title_fullStr Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients
title_full_unstemmed Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients
title_short Major influence of CD4 count at the initiation of cART on viral and immunological reservoir constitution in HIV-1 infected patients
title_sort major influence of cd4 count at the initiation of cart on viral and immunological reservoir constitution in hiv-1 infected patients
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4929778/
https://www.ncbi.nlm.nih.gov/pubmed/27363286
http://dx.doi.org/10.1186/s12977-016-0278-5
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