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Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy

Background: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV....

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Autores principales: Farcomeni, Stefania, Moretti, Sonia, Fimiani, Caterina, Sulekova, Lucia Fontanelli, Vescio, Fenicia, Sernicola, Leonardo, Maggiorella, Maria T., Remoli, Anna Lisa, Picconi, Orietta, Mosca, Luciana, Esvan, Rozenn, Biliotti, Elisa, Ciccozzi, Massimo, Sgarbanti, Marco, Taliani, Gloria, Borsetti, Alessandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623367/
https://www.ncbi.nlm.nih.gov/pubmed/34832642
http://dx.doi.org/10.3390/pathogens10111488
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author Farcomeni, Stefania
Moretti, Sonia
Fimiani, Caterina
Sulekova, Lucia Fontanelli
Vescio, Fenicia
Sernicola, Leonardo
Maggiorella, Maria T.
Remoli, Anna Lisa
Picconi, Orietta
Mosca, Luciana
Esvan, Rozenn
Biliotti, Elisa
Ciccozzi, Massimo
Sgarbanti, Marco
Taliani, Gloria
Borsetti, Alessandra
author_facet Farcomeni, Stefania
Moretti, Sonia
Fimiani, Caterina
Sulekova, Lucia Fontanelli
Vescio, Fenicia
Sernicola, Leonardo
Maggiorella, Maria T.
Remoli, Anna Lisa
Picconi, Orietta
Mosca, Luciana
Esvan, Rozenn
Biliotti, Elisa
Ciccozzi, Massimo
Sgarbanti, Marco
Taliani, Gloria
Borsetti, Alessandra
author_sort Farcomeni, Stefania
collection PubMed
description Background: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. Objectives: We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. Materials and Methods: Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). Results: All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-β, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. Conclusions: Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients.
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spelling pubmed-86233672021-11-27 Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy Farcomeni, Stefania Moretti, Sonia Fimiani, Caterina Sulekova, Lucia Fontanelli Vescio, Fenicia Sernicola, Leonardo Maggiorella, Maria T. Remoli, Anna Lisa Picconi, Orietta Mosca, Luciana Esvan, Rozenn Biliotti, Elisa Ciccozzi, Massimo Sgarbanti, Marco Taliani, Gloria Borsetti, Alessandra Pathogens Article Background: Direct-acting antivirals (DAAs) treatment, although highly efficacious for the treatment of hepatitis C virus (HCV) infection, may not completely reconstitute the HCV-mediated dysregulated immune system, especially in patients co-infected with human immunodeficiency virus (HIV) and HCV. Objectives: We aimed to evaluate the impact of HCV eradication following DAA therapy on the immune system and liver disease improvement through comparative monitoring of 10 HCV mono-infected and 10 HCV/HIV co-infected patients under combined antiretroviral therapy (cART). Early and late longitudinal phenotypic changes in peripheral blood mononuclear cell (PBMC) subsets, T-cell activation, differentiation and exhaustion, as well as inflammatory biomarkers, indoleamine 2-3 dioxygenase (IDO) activity, and liver stiffness, APRI and FIB-4 scores were assessed. Materials and Methods: Samples were obtained at baseline (T0), week 1 (T1), week 2 (T2), week 12 (T3, end of treatment, EOT), and month 9 (T4, end of follow-up, 36 weeks post EOT). Results: All patients achieved a sustained virological response (SVR 12) after DAA treatment. Overall, changes of the T-cell immune phenotypes were greater in HCV/HIV co-infected than in HCV mono-infected, due to an increase in CD4+ and CD8+ T-cell percentages and of CD8+ T-cell activation and memory markers, in particular at the end of follow-up. On the other end, HCV mono-infected showed changes in the activation profile and in the memory CD4+ T-cell compartment. In HCV/HIV co-infected, a decrease in the IDO activity by DAA treatment was observed; conversely, in HCV mono-infected, it resulted unmodified. Regarding inflammatory mediators, viral suppression was associated with a reduction in IP-10 levels, while interferon regulatory factor (IRF)-7, interferon (IFN)-β, and interferon (IFN)-γ levels were downregulated during therapy and increased post therapy. A decrease in liver stiffness, APRI, and FIB-4 scores was also observed. Conclusions: Our study suggests that, although patients achieved HCV eradication, the immune activation state in both HCV mono-infected and HCV/HIV co-infected patients remains elevated for a long time after the end of DAA therapy, despite an improvement of liver-specific outcomes, meanwhile highlighting the distinct immunophenotypic and inflammatory biomarker profile between the groups of patients. MDPI 2021-11-15 /pmc/articles/PMC8623367/ /pubmed/34832642 http://dx.doi.org/10.3390/pathogens10111488 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Farcomeni, Stefania
Moretti, Sonia
Fimiani, Caterina
Sulekova, Lucia Fontanelli
Vescio, Fenicia
Sernicola, Leonardo
Maggiorella, Maria T.
Remoli, Anna Lisa
Picconi, Orietta
Mosca, Luciana
Esvan, Rozenn
Biliotti, Elisa
Ciccozzi, Massimo
Sgarbanti, Marco
Taliani, Gloria
Borsetti, Alessandra
Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy
title Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy
title_full Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy
title_fullStr Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy
title_full_unstemmed Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy
title_short Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy
title_sort short- and long-term immunological responses in chronic hcv/hiv co-infected compared to hcv mono-infected patients after daa therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8623367/
https://www.ncbi.nlm.nih.gov/pubmed/34832642
http://dx.doi.org/10.3390/pathogens10111488
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