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J Acquir Immune Defic Syndr. 2016 Mar 1;71(3):254-62. doi: 10.1097/QAI.0000000000000859.

Influence of Hepatitis C Virus Sustained Virological Response on Immunosuppressive Tryptophan Catabolism in ART-Treated HIV/HCV Coinfected Patients.

Author information

1
*Chronic Viral Illnesses Service, McGill University Health Centre, Montreal, Quebec, Canada; †Currently, Département des Sciences Biologiques et Centre de recherche BioMed, Université du Québec à Montréal (UQAM), Québec, Canada; ‡Research Institute McGill University Health Centre, Montreal, Quebec, Canada; §Department of Laboratory Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands; ‖Research Department, School of Medicine, Universidad Iberoamericana, Santo Domingo, Dominican Republic; and ¶Division of Hematology, McGill University Health Centre, Montreal, Quebec, Canada.

Abstract

BACKGROUND:

We previously reported an association between tryptophan (Trp) catabolism and immune dysfunction in HIV monoinfection. Coinfection with HIV is associated with more rapid evolution of hepatitis C virus (HCV)-associated liver disease despite antiretroviral therapy (ART), possibly due to immune dysregulation. We hypothesized that liver fibrosis in HIV/HCV coinfection would be associated with immune dysfunction and alterations in Trp metabolism.

METHODS:

Trp catabolism and inflammatory soluble markers were assessed in plasma samples from ART-treated HIV/HCV-coinfected patients (n = 90) compared with ART-treated HIV-monoinfected patients and noninfected subjects. Furthermore, 17 additional coinfected patients with sustained virological response (SVR) were assessed longitudinally 6 months after completion of interferon-α/ribavirin treatment.

RESULTS:

HIV/HCV patients had higher Trp catabolism compared with HIV-monoinfected and healthy individuals. Elevated kynurenine levels in HIV/HCV patients with liver fibrosis correlated with the prognostic aspartate aminotransaminase to platelet ratio (APRI scores) and insulin levels. Furthermore, HIV/HCV patients had elevated levels of disease progression markers interleukin-6 and induced protein 10 and shared similar levels of markers of microbial translocation (intestinal fatty acid-binding protein, soluble CD14 and lipopolysaccharide-binding protein) compared with HIV-monoinfected and healthy individuals. Successful HCV treatment improved APRI score and markers of disease progression and microbial translocation although elevated Trp catabolism remained unchanged 6 months after SVR.

CONCLUSION:

ART-treated HIV/HCV-coinfected patients had elevated immunosuppressive Trp catabolism when compared with monoinfected HIV-treated patients, which did not normalize after SVR. These findings suggest that a necroinflammatory liver syndrome persists through inflammation by Trp catabolism after 6 month of SVR.

PMID:
26436613
PMCID:
PMC4770371
DOI:
10.1097/QAI.0000000000000859
[Indexed for MEDLINE]
Free PMC Article

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