Hepatitis C virus drives increased type I interferon-associated impairments associated with fibrosis severity in antiretroviral treatment-treated HIV-1-hepatitis C virus-coinfected individuals

作者：Grie**eck Morgane; Valantin Marc Antoine; Lacombe Karine; Samri Hassimi Assia; Bottero Julie; Blanc Catherine; Sbihi Zineb; Zoorob Rima; Katlama Christine; Guiguet Marguerite; Altfeld Marcus; Autran Brigitte^*

来源：AIDS, 2017, 31(9): 1223-1234.

DOI：10.1097/QAD.0000000000001455

• hepatitis C virus
• HIV
• interferon a
• inflammation
• interferon-stimulated genes
• IP-10
• plasmacytoid dendritic cell

Background: Viral coinfections might contribute to the increased immune activation and inflammation that persist in antiretroviral treatment (ART)-treated HIV-1 patients. We investigated whether the hepatitis C virus (HCV) coinfection contributes to such alterations by impairing the plasmacytoid dendritic cell (pDC) IFN alpha/TLR7 pathway in a highly homogeneous group of ART-treated HIV-1-HCV-coinfected patients.
Methods: Twenty-nine HIV-1-infected patients with fully suppressive ART were included, 15 of whom being HCV-coinfected with mild-to-moderate fibrosis and matched for their HIV-1 disease, and 13 control healthy donors. Cellular activation, plasma levels of inflammatory cytokines and pDC transcriptome associated with IFNa/TLR7 pathway were characterized.
Results: Higher plasma levels of type-I interferon (IFN)-associated cytokines [interferon gamma-induced protein 10 (IP-10), MIP-1 beta, IL-8 and IFN-inducible T-cell alpha chemoattractant) were observed in HIV-1-HCV-coinfected than in HIV-1-monoinfected patients (P = 0.0007, 0.028, 0.028 and 0.035, respectively). The pDCs and T cells displayed a more exhausted (LAG-3+ and CD57+, respectively) phenotype. The pDC IFN alpha pathway (defined by phosphorylated STAT1 expression) was constitutively activated in all patients, irrespective of HCV coinfection. Expression of interferon-stimulated genes (ISGs) EI2AK2, ISG15, Mx1 and IFI44 was increased in pDCs from HIV-1-HCV-coinfected individuals and was correlated with fibrosis score (Fibroscan, www.echosens.com, Paris, France and aspartate-aminotransferase/platelet-ratio index score, P = 0.026 and 0.019, respectively). Plasma levels of IP-10, STAT1 expression in pDCs and Mx1 mRNA levels in pDCs decreased after interferon-free anti-HCV treatment.
Conclusion: HCV replication appears to drive increases in type-I IFN-associated inflammation and ISGs expression in pDCs, in association with fibrosis severity in ART-treated HIV-1-infected patients with mild-to-moderate fibrosis. Preliminary results indicate reduction of these alterations with earlier interferon-free anti-HCV treatment in those patients.

• 出版日期2017-6-1