Evolution of T-cell responses to hepatitis C virus (HCV) during pegylated interferon plus ribavirin treatment in HCV-monoinfected and in HCV/HIV-coinfected patients

Antivir Ther. 2007;12(4):459-68.

Abstract

Background: The role of T-cell immunity in chronic hepatitis C virus (HCV) infection remains controversial. As in HIV infection, virus replication could drive or be contained by T-cell immunity. We have examined the effect of HIV coinfection and of suppression of HCV replication with therapy on HCV-specific T-cell responses.

Patients and methods: Thirty-five patients with chronic hepatitis C (17 coinfected with HIV) initiating anti-HCV therapy were analysed. HCV-specific responses were assessed at different time points using intracellular interferon-gamma staining in response to a panel of overlapping peptides comprising E2, NS3, NS5a and NS5b HCV proteins.

Results: At baseline, HCV-specific responses were significantly lower in HIV-coinfected patients. At week 12 of therapy, CD8+ T-cell responses against all HCV proteins significantly decreased in HCV-monoinfected patients and this was maintained throughout the follow-up period. Although the same trend occurred in the HIV-coinfected group, differences were not significant. CD4+ T-cell responses against NS3 significantly diminished in the HCV-monoinfected group, whereas in coinfected patients CD4+ T-cell responses were low at baseline and did not experience any significant variation.

Conclusions: HCV-specific T-cell responses are lower in HIV-coinfected patients and vanish following complete suppression of HCV replication under successful HCV therapy, suggesting that they are dependent on continuous antiqenic stimulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • HIV Infections / complications*
  • Hepacivirus / immunology*
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Recombinant Proteins
  • Ribavirin / therapeutic use*
  • T-Lymphocytes / immunology*

Substances

  • Antiviral Agents
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a