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Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial

BACKGROUND: Ongoing HIV-1 replication in lymphoid cells is one explanation of the persistence of HIV-1 reservoirs despite highly active antiretroviral therapy (cART). We tested the potential of cART intensification by Maraviroc plus Raltegravir to decrease proviral HIV-1 DNA levels in lymphoid cells...

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Autores principales: Lafeuillade, Alain, Assi, Assi, Poggi, Cécile, Bresson-Cuquemelle, Caroline, Jullian, Eric, Tamalet, Catherine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197239/
https://www.ncbi.nlm.nih.gov/pubmed/25320633
http://dx.doi.org/10.1186/1742-6405-11-33
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author Lafeuillade, Alain
Assi, Assi
Poggi, Cécile
Bresson-Cuquemelle, Caroline
Jullian, Eric
Tamalet, Catherine
author_facet Lafeuillade, Alain
Assi, Assi
Poggi, Cécile
Bresson-Cuquemelle, Caroline
Jullian, Eric
Tamalet, Catherine
author_sort Lafeuillade, Alain
collection PubMed
description BACKGROUND: Ongoing HIV-1 replication in lymphoid cells is one explanation of the persistence of HIV-1 reservoirs despite highly active antiretroviral therapy (cART). We tested the potential of cART intensification by Maraviroc plus Raltegravir to decrease proviral HIV-1 DNA levels in lymphoid cells during a randomized trial. PATIENTS AND METHODS: We randomly assigned for 48 weeks 22 patients to continue their current first line regimen of Truvada® plus Kaletra® or intensify it with Maraviroc and Raltegravir. The primary objective was to obtain a 50% decrease in proviral HIV-1 DNA levels in lymphoid cells with intensification. Blood samples were drawn at W-2, W0, W2, W4, W12, W24 and W48. Plasma viremia, cellular proviral DNA and cellular RNA, 2-LTR circles and lymphocytes subsets were assayed using validated methods. Patients in the intensified group underwent a gut biopsy at baseline and W48 to measure proviral DNA levels. Statistical analysis used parametric and non-parametric tests. RESULTS: Ten patients in each arm completed the trial. The 2 populations were comparable at baseline. No change in the reservoir size was observed in the intensified arm compared to the control arm measured in peripheral blood mononuclear cells (PBMCs). No change in the reservoir size was observed in gut proviral DNA in the intensified arm. In this group, no increase in 2-LTR circles was observed as early as 2 weeks after intensification and no change was found in residual plasma RNA levels measured by the single copy assay. However, a decrease in CD8(+) T cells activation was observed at 24 and 48 weeks, as well as in PBMCs HIV-1 RNA levels. CONCLUSION: We conclude that the intensification of a Protease Inhibitor regimen with Maraviroc and Raltegravir does not impact the blood proviral DNA reservoir of HIV but can decrease the cell-associated HIV RNA, the CD8 activation and has a possible impact on rectal proviral HIV DNA in some patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT00935480
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spelling pubmed-41972392014-10-16 Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial Lafeuillade, Alain Assi, Assi Poggi, Cécile Bresson-Cuquemelle, Caroline Jullian, Eric Tamalet, Catherine AIDS Res Ther Research BACKGROUND: Ongoing HIV-1 replication in lymphoid cells is one explanation of the persistence of HIV-1 reservoirs despite highly active antiretroviral therapy (cART). We tested the potential of cART intensification by Maraviroc plus Raltegravir to decrease proviral HIV-1 DNA levels in lymphoid cells during a randomized trial. PATIENTS AND METHODS: We randomly assigned for 48 weeks 22 patients to continue their current first line regimen of Truvada® plus Kaletra® or intensify it with Maraviroc and Raltegravir. The primary objective was to obtain a 50% decrease in proviral HIV-1 DNA levels in lymphoid cells with intensification. Blood samples were drawn at W-2, W0, W2, W4, W12, W24 and W48. Plasma viremia, cellular proviral DNA and cellular RNA, 2-LTR circles and lymphocytes subsets were assayed using validated methods. Patients in the intensified group underwent a gut biopsy at baseline and W48 to measure proviral DNA levels. Statistical analysis used parametric and non-parametric tests. RESULTS: Ten patients in each arm completed the trial. The 2 populations were comparable at baseline. No change in the reservoir size was observed in the intensified arm compared to the control arm measured in peripheral blood mononuclear cells (PBMCs). No change in the reservoir size was observed in gut proviral DNA in the intensified arm. In this group, no increase in 2-LTR circles was observed as early as 2 weeks after intensification and no change was found in residual plasma RNA levels measured by the single copy assay. However, a decrease in CD8(+) T cells activation was observed at 24 and 48 weeks, as well as in PBMCs HIV-1 RNA levels. CONCLUSION: We conclude that the intensification of a Protease Inhibitor regimen with Maraviroc and Raltegravir does not impact the blood proviral DNA reservoir of HIV but can decrease the cell-associated HIV RNA, the CD8 activation and has a possible impact on rectal proviral HIV DNA in some patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier number NCT00935480 BioMed Central 2014-10-07 /pmc/articles/PMC4197239/ /pubmed/25320633 http://dx.doi.org/10.1186/1742-6405-11-33 Text en © Lafeuillade et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. 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
Lafeuillade, Alain
Assi, Assi
Poggi, Cécile
Bresson-Cuquemelle, Caroline
Jullian, Eric
Tamalet, Catherine
Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial
title Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial
title_full Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial
title_fullStr Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial
title_full_unstemmed Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial
title_short Failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically HIV-1 infected patients to reduce the viral reservoir: the IntensHIV randomized trial
title_sort failure of combined antiretroviral therapy intensification with maraviroc and raltegravir in chronically hiv-1 infected patients to reduce the viral reservoir: the intenshiv randomized trial
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4197239/
https://www.ncbi.nlm.nih.gov/pubmed/25320633
http://dx.doi.org/10.1186/1742-6405-11-33
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