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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2021
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oai:doaj.org-article:057f838d1acd46889c08a28092015c522021-11-25T18:38:38ZShort- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy10.3390/pathogens101114882076-0817https://doaj.org/article/057f838d1acd46889c08a28092015c522021-11-01T00:00:00Zhttps://www.mdpi.com/2076-0817/10/11/1488https://doaj.org/toc/2076-0817Background: 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.Stefania FarcomeniSonia MorettiCaterina FimianiLucia Fontanelli SulekovaFenicia VescioLeonardo SernicolaMaria T. MaggiorellaAnna Lisa RemoliOrietta PicconiLuciana MoscaRozenn EsvanElisa BiliottiMassimo CiccozziMarco SgarbantiGloria TalianiAlessandra BorsettiMDPI AGarticleHCV infectionHCV/HIV coinfectionDAA direct-acting antiviralsinterferon-stimulated gene (ISG) expressionindoleamine 2-3 dioxygenase (IDO) activityimmune activationMedicineRENPathogens, Vol 10, Iss 1488, p 1488 (2021) |
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EN |
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HCV infection HCV/HIV coinfection DAA direct-acting antivirals interferon-stimulated gene (ISG) expression indoleamine 2-3 dioxygenase (IDO) activity immune activation Medicine R |
| spellingShingle |
HCV infection HCV/HIV coinfection DAA direct-acting antivirals interferon-stimulated gene (ISG) expression indoleamine 2-3 dioxygenase (IDO) activity immune activation Medicine R Stefania Farcomeni Sonia Moretti Caterina Fimiani Lucia Fontanelli Sulekova Fenicia Vescio Leonardo Sernicola Maria T. Maggiorella Anna Lisa Remoli Orietta Picconi Luciana Mosca Rozenn Esvan Elisa Biliotti Massimo Ciccozzi Marco Sgarbanti Gloria Taliani Alessandra Borsetti Short- and Long-Term Immunological Responses in Chronic HCV/HIV Co-Infected Compared to HCV Mono-Infected Patients after DAA Therapy |
| 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. |
| format |
article |
| author |
Stefania Farcomeni Sonia Moretti Caterina Fimiani Lucia Fontanelli Sulekova Fenicia Vescio Leonardo Sernicola Maria T. Maggiorella Anna Lisa Remoli Orietta Picconi Luciana Mosca Rozenn Esvan Elisa Biliotti Massimo Ciccozzi Marco Sgarbanti Gloria Taliani Alessandra Borsetti |
| author_facet |
Stefania Farcomeni Sonia Moretti Caterina Fimiani Lucia Fontanelli Sulekova Fenicia Vescio Leonardo Sernicola Maria T. Maggiorella Anna Lisa Remoli Orietta Picconi Luciana Mosca Rozenn Esvan Elisa Biliotti Massimo Ciccozzi Marco Sgarbanti Gloria Taliani Alessandra Borsetti |
| author_sort |
Stefania Farcomeni |
| title |
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_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_sort |
short- and long-term immunological responses in chronic hcv/hiv co-infected compared to hcv mono-infected patients after daa therapy |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/057f838d1acd46889c08a28092015c52 |
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