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

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

doi:10.3390/pathogens10111488

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

Pathogens. 2021 Nov 15;10(11):1488. doi: 10.3390/pathogens10111488.

Authors

Stefania Farcomeni¹, Sonia Moretti¹, Caterina Fimiani², Lucia Fontanelli Sulekova³, Fenicia Vescio⁴, Leonardo Sernicola¹, Maria T Maggiorella¹, Anna Lisa Remoli⁴, Orietta Picconi¹, Luciana Mosca⁵, Rozenn Esvan², Elisa Biliotti⁶, Massimo Ciccozzi⁷, Marco Sgarbanti⁴, Gloria Taliani⁸, Alessandra Borsetti¹

Affiliations

¹ National HIV/AIDS Research Center, Istituto Superiore di Sanità, 00161 Rome, Italy.
² Department of Public Health and Infectious Diseases, "Sapienza" University of Rome, 00161 Rome, Italy.
³ Department of Translation and Precision Medicine, "Sapienza" University of Rome, 00161 Rome, Italy.
⁴ Department of Infectious Diseases, Istituto Superiore di Sanità, 00161 Rome, Italy.
⁵ Department of Biochemical Sciences, "Sapienza" University of Rome, 00161 Rome, Italy.
⁶ Department of Clinical Medicine, Policlinico Umberto I, "Sapienza" University of Rome, 00161 Rome, Italy.
⁷ Medical Statistics and Molecular Epidemiology Unit, University Campus Bio-Medico of Rome, 00161 Rome, Italy.
⁸ Chronic Infectious Diseases Unit, Policlinico Umberto I, "Sapienza" University of Rome, 00161 Rome, Italy.

Abstract

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.

Keywords: DAA direct-acting antivirals; HCV infection; HCV/HIV coinfection; immune activation; indoleamine 2-3 dioxygenase (IDO) activity; interferon-stimulated gene (ISG) expression.