Abstract

BackgroundMicrobial translocation (MT) contributes to immune activation during HIV and HCV infections. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) could predict anti-HCV treatment outcome.MethodsPlasma from 78 HIV-infected patients was evaluated for LPS, LBP and sCD14. The patients starting anti-HCV treatment (with ongoing antiretroviral (ART) treatment) were categorized into sustained viral responders (SVR; n = 21) or non-responders (NR; n = 15) based on treatment outcome. ART starting subjects—were categorized into chronically HCV-infected (CH; n = 24) and mono-infected (HIV; n = 18), based on the HCV infection status. Samples were collected before start (at baseline) of pegylated-interferon-alpha/ribavirin (peg-IFN/RBV) or antiretroviral-therapy and two years after treatment start (at follow up). χ2–test, non-parametric statistics and logistic regression were applied to determine the associations with treatment response and changes of the soluble markers.ResultsPlasma levels of LPS and sCD14 were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up. Elevated levels of LBP were present in patients with HIV and HIV/HCV co-infection and were reduced by ART. Additionally, higher levels of LBP were present at baseline in NR vs. SVR. Higher levels of LBP at baseline were associated with non-response to peg-IFN/RBV treatment in both bivariate (OR: 0.19 95% CI: 0.06–0.31, p = 0.004) and multivariate analysis (OR: 1.43, 95% CI: 1.1–1.86, p = 0.07).ConclusionIn HIV/HCV co-infected patients high baseline LBP levels are associated with non-response to peg-IFN/RBV therapy. Plasma LBP (decreased by ART) may be a more relevant MT marker than LPS and sCD14.

Highlights

  • Co-infection with hepatitis C virus (HCV) is common in patients with HIV-1 mono-infected (HIV)-1 infection and HCV associated liver failure is a leading cause of death in HIV/HCV infected patients [1]

  • We investigated the kinetics of Microbial translocation (MT) markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and soluble CD14 could predict anti-HCV treatment outcome

  • Plasma levels of LPS and soluble CD14 (sCD14) were elevated in all subjects before antiviral-treatment but remained unchanged at follow-up

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Summary

Introduction

Co-infection with hepatitis C virus (HCV) is common in patients with HIV-1 infection and HCV associated liver failure is a leading cause of death in HIV/HCV infected patients [1]. The pathological events during the co-infection are not fully revealed, most relevant mechanisms include direct viral effect, dysregulation of cytokine network / inflammation, increased oxidative stress and hepatocyte apoptosis [3]. These processes lead to acceleration of liver inflammation giving rise to enhanced fibrosis progression in HIV/HCV co-infected individuals. Systemic inflammation associated with gut derived microbial products has been described during both HIV-1 [4] and HCV infections [5]. We investigated the kinetics of MT markers during anti-HCV and anti-HIV treatments, and if baseline plasma levels of lipopolysaccharide (LPS), lipopolysaccharide binding protein (LBP) and soluble CD14 (sCD14) could predict anti-HCV treatment outcome

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