Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients

1) Background: The role of hepatitis C virus (HCV) co-infection on the T-cell homeostasis disturbances in human immunodeficiency virus (HIV)-infected patients as well as its reversion after HCV eradication with direct acting antivirals (DAAs) therapy has not been yet clarified. We extensively analyz...

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Autores: Restrepo, Clara, Álvarez, Beatriz, Valencia Delfa, José Luis, García, Marcial, Navarrete Muñoz, María A., Ligos, José M., Cabello, Alfonso, Prieto Martínez, Laura Beatriz, Nistal, Sara, Montoya Redondo, María Luisa, Górgolas, Miguel, Rallón, Norma, Benito, José M.
Formato: artículo
Fecha de publicación:2020
País:España
Recursos:Universidad Complutense de Madrid (UCM)
Repositorio:Docta Complutense
Idioma:inglés
OAI Identifier:oai:docta.ucm.es:20.500.14352/8364
Acesso em linha:https://hdl.handle.net/20.500.14352/8364
Access Level:acceso abierto
Palavra-chave:HIV/HCV coinfection
T-cell homeostasis disturbances
liver stiffness
immune restoration
DAAs-based therapy
Enfermedades infecciosas
Gastroenterología y hepatología
Inmunología
3205.05 Enfermedades Infecciosas
3205.03 Gastroenterología
2412 Inmunología
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spelling Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected PatientsRestrepo, ClaraÁlvarez, BeatrizValencia Delfa, José LuisGarcía, MarcialNavarrete Muñoz, María A.Ligos, José M.Cabello, AlfonsoPrieto Martínez, Laura BeatrizNistal, SaraMontoya Redondo, María LuisaGórgolas, MiguelRallón, NormaBenito, José M.HIV/HCV coinfectionT-cell homeostasis disturbancesliver stiffnessimmune restorationDAAs-based therapyEnfermedades infecciosasGastroenterología y hepatologíaInmunología3205.05 Enfermedades Infecciosas3205.03 Gastroenterología2412 Inmunología1) Background: The role of hepatitis C virus (HCV) co-infection on the T-cell homeostasis disturbances in human immunodeficiency virus (HIV)-infected patients as well as its reversion after HCV eradication with direct acting antivirals (DAAs) therapy has not been yet clarified. We extensively analyzed the effect of HCV co-infection on immune parameters of HIV pathogenesis and its evolution after HCV eradication with DAAs. (2) Methods: Seventy individuals were included in the study—25 HIV-monoinfected patients, 25 HIV/HCV-coinfected patients and 20 HIV and HCV seronegative subjects. All patients were on antiretroviral therapy and undetectable HIV-viremia. Immune parameters, such as maturation, activation, apoptosis, senescence and exhaustion of T-cells were assessed by flow cytometry. Cross-sectional and longitudinal (comparing pre- and post-DAAs data in HIV/HCV coinfected patients) analyses were performed. Univariate and multivariate (general linear model and canonical discriminant analysis -CDA-) analyses were used to assess differences between groups. (3) Results—The CDA was able to clearly separate HIV/HCV coinfected from HIV-monoinfected patients, showing a more disturbed T-cells homeostasis in HIV/HCV patients, especially activation and exhaustion of T-cells. Interestingly, those perturbations were more marked in HIV/HCV patients with increased liver stiffness. Eradication of HCV with DAAs restored some but not all the T-cells homeostasis disturbances, with activation and exhaustion of effector CD8 T-cells remaining significantly increased three months after HCV eradication. (4) Conclusions—HCV co-infection significantly impacts on several immune markers of HIV pathogenesis, especially in patients with increased liver stiffness. Eradication of HCV with DAAs ameliorates but does not completely normalize these alterations. It is of utmost relevance to explore other mechanisms underlying the immune damage observed in HIV/HCV coinfected patients with control of both HIV and HCV replication.MDPIUniversidad Complutense de Madrid20202020-09-1520202020-09-15journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.14352/8364reponame:Docta Complutenseinstname:Universidad Complutense de Madrid (UCM)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Atribución 3.0 Españahttps://creativecommons.org/licenses/by/3.0/es/info:eu-repo/semantics/openAccessoai:docta.ucm.es:20.500.14352/83642026-06-02T12:44:21Z
dc.title.none.fl_str_mv Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients
title Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients
spellingShingle Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients
Restrepo, Clara
HIV/HCV coinfection
T-cell homeostasis disturbances
liver stiffness
immune restoration
DAAs-based therapy
Enfermedades infecciosas
Gastroenterología y hepatología
Inmunología
3205.05 Enfermedades Infecciosas
3205.03 Gastroenterología
2412 Inmunología
title_short Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients
title_full Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients
title_fullStr Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients
title_full_unstemmed Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients
title_sort Both HCV Infection and Elevated Liver Stiffness Significantly Impacts on Several Parameters of T-Cells Homeostasis in HIV-Infected Patients
dc.creator.none.fl_str_mv Restrepo, Clara
Álvarez, Beatriz
Valencia Delfa, José Luis
García, Marcial
Navarrete Muñoz, María A.
Ligos, José M.
Cabello, Alfonso
Prieto Martínez, Laura Beatriz
Nistal, Sara
Montoya Redondo, María Luisa
Górgolas, Miguel
Rallón, Norma
Benito, José M.
author Restrepo, Clara
author_facet Restrepo, Clara
Álvarez, Beatriz
Valencia Delfa, José Luis
García, Marcial
Navarrete Muñoz, María A.
Ligos, José M.
Cabello, Alfonso
Prieto Martínez, Laura Beatriz
Nistal, Sara
Montoya Redondo, María Luisa
Górgolas, Miguel
Rallón, Norma
Benito, José M.
author_role author
author2 Álvarez, Beatriz
Valencia Delfa, José Luis
García, Marcial
Navarrete Muñoz, María A.
Ligos, José M.
Cabello, Alfonso
Prieto Martínez, Laura Beatriz
Nistal, Sara
Montoya Redondo, María Luisa
Górgolas, Miguel
Rallón, Norma
Benito, José M.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universidad Complutense de Madrid
dc.subject.none.fl_str_mv HIV/HCV coinfection
T-cell homeostasis disturbances
liver stiffness
immune restoration
DAAs-based therapy
Enfermedades infecciosas
Gastroenterología y hepatología
Inmunología
3205.05 Enfermedades Infecciosas
3205.03 Gastroenterología
2412 Inmunología
topic HIV/HCV coinfection
T-cell homeostasis disturbances
liver stiffness
immune restoration
DAAs-based therapy
Enfermedades infecciosas
Gastroenterología y hepatología
Inmunología
3205.05 Enfermedades Infecciosas
3205.03 Gastroenterología
2412 Inmunología
description 1) Background: The role of hepatitis C virus (HCV) co-infection on the T-cell homeostasis disturbances in human immunodeficiency virus (HIV)-infected patients as well as its reversion after HCV eradication with direct acting antivirals (DAAs) therapy has not been yet clarified. We extensively analyzed the effect of HCV co-infection on immune parameters of HIV pathogenesis and its evolution after HCV eradication with DAAs. (2) Methods: Seventy individuals were included in the study—25 HIV-monoinfected patients, 25 HIV/HCV-coinfected patients and 20 HIV and HCV seronegative subjects. All patients were on antiretroviral therapy and undetectable HIV-viremia. Immune parameters, such as maturation, activation, apoptosis, senescence and exhaustion of T-cells were assessed by flow cytometry. Cross-sectional and longitudinal (comparing pre- and post-DAAs data in HIV/HCV coinfected patients) analyses were performed. Univariate and multivariate (general linear model and canonical discriminant analysis -CDA-) analyses were used to assess differences between groups. (3) Results—The CDA was able to clearly separate HIV/HCV coinfected from HIV-monoinfected patients, showing a more disturbed T-cells homeostasis in HIV/HCV patients, especially activation and exhaustion of T-cells. Interestingly, those perturbations were more marked in HIV/HCV patients with increased liver stiffness. Eradication of HCV with DAAs restored some but not all the T-cells homeostasis disturbances, with activation and exhaustion of effector CD8 T-cells remaining significantly increased three months after HCV eradication. (4) Conclusions—HCV co-infection significantly impacts on several immune markers of HIV pathogenesis, especially in patients with increased liver stiffness. Eradication of HCV with DAAs ameliorates but does not completely normalize these alterations. It is of utmost relevance to explore other mechanisms underlying the immune damage observed in HIV/HCV coinfected patients with control of both HIV and HCV replication.
publishDate 2020
dc.date.none.fl_str_mv 2020
2020-09-15
2020
2020-09-15
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/20.500.14352/8364
url https://hdl.handle.net/20.500.14352/8364
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Atribución 3.0 España
https://creativecommons.org/licenses/by/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Docta Complutense
instname:Universidad Complutense de Madrid (UCM)
instname_str Universidad Complutense de Madrid (UCM)
reponame_str Docta Complutense
collection Docta Complutense
repository.name.fl_str_mv
repository.mail.fl_str_mv
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