Low levels of microbial translocation marker LBP are associated with sustained viral response after anti-HCV treatment in HIV-1/HCV co-infected patients

PLoS One. 2015 Mar 18;10(3):e0118643. doi: 10.1371/journal.pone.0118643. eCollection 2015.

Abstract

Background: Microbial 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.

Methods: Plasma 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.

Results: Plasma 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).

Conclusion: In 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins
  • Adult
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use
  • Aspartate Aminotransferases / metabolism
  • Biomarkers / blood
  • Carrier Proteins / blood*
  • Coinfection / drug therapy*
  • Coinfection / immunology
  • Coinfection / metabolism
  • Coinfection / microbiology*
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / metabolism
  • HIV Infections / microbiology*
  • HIV-1 / drug effects
  • HIV-1 / physiology
  • Hepacivirus / drug effects
  • Hepacivirus / physiology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / microbiology*
  • Humans
  • Interferon-alpha / pharmacology
  • Interferon-alpha / therapeutic use
  • Kinetics
  • Lipopolysaccharide Receptors / blood
  • Lipopolysaccharide Receptors / chemistry
  • Lipopolysaccharides / blood
  • Male
  • Membrane Glycoproteins / blood*
  • Middle Aged
  • Retrospective Studies
  • Ribavirin / pharmacology
  • Ribavirin / therapeutic use
  • Solubility
  • Time Factors
  • Treatment Outcome

Substances

  • Acute-Phase Proteins
  • Anti-HIV Agents
  • Biomarkers
  • Carrier Proteins
  • Interferon-alpha
  • Lipopolysaccharide Receptors
  • Lipopolysaccharides
  • Membrane Glycoproteins
  • lipopolysaccharide-binding protein
  • Ribavirin
  • Aspartate Aminotransferases

Grant support

This study was supported by grants from Swedish society for medical research, Åke Wiberg foundation, Swedish Research Council and Karolinska Institutet/Södertörn University (postdoctoral grant to JN). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.