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Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS

BACKGROUND: HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus therapeutic agents able to target these reservo...

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Autores principales: Shytaj, Iart Luca, Chirullo, Barbara, Wagner, Wendeline, Ferrari, Maria G, Sgarbanti, Rossella, Corte, Alessandro Della, LaBranche, Celia, Lopalco, Lucia, Palamara, Anna Teresa, Montefiori, David, Lewis, Mark G, Garaci, Enrico, Savarino, Andrea
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748827/
https://www.ncbi.nlm.nih.gov/pubmed/23866829
http://dx.doi.org/10.1186/1742-4690-10-71
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author Shytaj, Iart Luca
Chirullo, Barbara
Wagner, Wendeline
Ferrari, Maria G
Sgarbanti, Rossella
Corte, Alessandro Della
LaBranche, Celia
Lopalco, Lucia
Palamara, Anna Teresa
Montefiori, David
Lewis, Mark G
Garaci, Enrico
Savarino, Andrea
author_facet Shytaj, Iart Luca
Chirullo, Barbara
Wagner, Wendeline
Ferrari, Maria G
Sgarbanti, Rossella
Corte, Alessandro Della
LaBranche, Celia
Lopalco, Lucia
Palamara, Anna Teresa
Montefiori, David
Lewis, Mark G
Garaci, Enrico
Savarino, Andrea
author_sort Shytaj, Iart Luca
collection PubMed
description BACKGROUND: HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus therapeutic agents able to target these reservoirs are needed. One such agent, auranofin, has recently been shown to decrease the memory T-cell reservoir in chronically SIVmac251-infected macaques. Moreover, auranofin could synergize with a fully suppressive ART protocol and induce a drug-free post-therapy containment of viremia. RESULTS: We administered buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis currently in clinical trials for cancer, in combination with auranofin to chronically SIVmac251-infected macaques under highly-intensified ART (H-iART). The ART/auranofin/BSO therapeutic protocol was followed, after therapy suspension, by a significant decrease of viral RNA and DNA in peripheral blood as compared to pre-therapy levels. Drug-free post-therapy control of the infection was achieved in animals with pre-therapy viral loads ranging from values comparable to average human set points to levels largely higher. This control was dependent on the presence CD8(+) cells and associated with enhanced levels of cell-mediated immune responses. CONCLUSIONS: The level of post-therapy viral set point reduction achieved in this study is the largest reported so far in chronically SIVmac251-infected macaques and may represent a promising strategy to improve over the current “ART for life” plight.
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spelling pubmed-37488272013-08-22 Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS Shytaj, Iart Luca Chirullo, Barbara Wagner, Wendeline Ferrari, Maria G Sgarbanti, Rossella Corte, Alessandro Della LaBranche, Celia Lopalco, Lucia Palamara, Anna Teresa Montefiori, David Lewis, Mark G Garaci, Enrico Savarino, Andrea Retrovirology Research BACKGROUND: HIV infection persists despite antiretroviral treatment (ART) and is reignited as soon as therapies are suspended. This vicious cycle is fueled by the persistence of viral reservoirs that are invulnerable to standard ART protocols, and thus therapeutic agents able to target these reservoirs are needed. One such agent, auranofin, has recently been shown to decrease the memory T-cell reservoir in chronically SIVmac251-infected macaques. Moreover, auranofin could synergize with a fully suppressive ART protocol and induce a drug-free post-therapy containment of viremia. RESULTS: We administered buthionine sulfoximine (BSO), an inhibitor of glutathione synthesis currently in clinical trials for cancer, in combination with auranofin to chronically SIVmac251-infected macaques under highly-intensified ART (H-iART). The ART/auranofin/BSO therapeutic protocol was followed, after therapy suspension, by a significant decrease of viral RNA and DNA in peripheral blood as compared to pre-therapy levels. Drug-free post-therapy control of the infection was achieved in animals with pre-therapy viral loads ranging from values comparable to average human set points to levels largely higher. This control was dependent on the presence CD8(+) cells and associated with enhanced levels of cell-mediated immune responses. CONCLUSIONS: The level of post-therapy viral set point reduction achieved in this study is the largest reported so far in chronically SIVmac251-infected macaques and may represent a promising strategy to improve over the current “ART for life” plight. BioMed Central 2013-07-16 /pmc/articles/PMC3748827/ /pubmed/23866829 http://dx.doi.org/10.1186/1742-4690-10-71 Text en Copyright © 2013 Shytaj 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
Shytaj, Iart Luca
Chirullo, Barbara
Wagner, Wendeline
Ferrari, Maria G
Sgarbanti, Rossella
Corte, Alessandro Della
LaBranche, Celia
Lopalco, Lucia
Palamara, Anna Teresa
Montefiori, David
Lewis, Mark G
Garaci, Enrico
Savarino, Andrea
Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS
title Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS
title_full Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS
title_fullStr Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS
title_full_unstemmed Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS
title_short Investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian AIDS
title_sort investigational treatment suspension and enhanced cell-mediated immunity at rebound followed by drug-free remission of simian aids
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3748827/
https://www.ncbi.nlm.nih.gov/pubmed/23866829
http://dx.doi.org/10.1186/1742-4690-10-71
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