Cellular immune responses to HCV core increase and HCV RNA levels decrease during successful antiretroviral therapy

Gut. 2010 Sep;59(9):1252-8. doi: 10.1136/gut.2009.205971. Epub 2010 Jul 26.

Abstract

Background: Hepatitis C virus (HCV) infection is a major cause of morbidity in HIV infected individuals. Coinfection with HIV is associated with diminished HCV-specific immune responses and higher HCV RNA levels.

Aims: To investigate whether long-term combination antiretroviral therapy (cART) restores HCV-specific T cell responses and improves the control of HCV replication.

Methods: T cell responses were evaluated longitudinally in 80 HIV/HCV coinfected individuals by ex vivo interferon-gamma-ELISpot responses to HCV core peptides, that predominantly stimulate CD4(+) T cells. HCV RNA levels were assessed by real-time PCR in 114 individuals.

Results: The proportion of individuals with detectable T cell responses to HCV core peptides was 19% before starting cART, 24% in the first year on cART and increased significantly to 45% and 49% after 33 and 70 months on cART (p=0.001). HCV-specific immune responses increased in individuals with chronic (+31%) and spontaneously cleared HCV infection (+30%). Median HCV RNA levels before starting cART were 6.5 log(10) IU/ml. During long-term cART, median HCV-RNA levels slightly decreased compared to pre-cART levels (-0.3 log10 IU/ml, p=0.02).

Conclusions: Successful cART is associated with increasing cellular immune responses to HCV core peptides and with a slight long-term decrease in HCV RNA levels. These findings are in line with the favourable clinical effects of cART on the natural history of hepatitis C and with the current recommendation to start cART earlier in HCV/HIV coinfected individuals.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Cohort Studies
  • Female
  • HIV Infections / complications
  • HIV Infections / drug therapy
  • HIV Infections / immunology
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepacivirus / immunology*
  • Hepacivirus / isolation & purification
  • Hepatitis C Antigens / immunology
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / immunology*
  • Humans
  • Immunity, Cellular / drug effects
  • Interferon-gamma / biosynthesis
  • Longitudinal Studies
  • Male
  • RNA, Viral / blood
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • Viral Core Proteins / immunology
  • Viral Load / drug effects

Substances

  • Anti-HIV Agents
  • Hepatitis C Antigens
  • RNA, Viral
  • Viral Core Proteins
  • Interferon-gamma