Transient liver injury associated with the early recovery of HCV-specific T-cell responses and HCV rebound in HIV-1/HCV coinfected patients undergoing highly active antiretroviral therapy

J Acquir Immune Defic Syndr. 2013 Feb 1;62(2):135-42. doi: 10.1097/QAI.0b013e3182752d20.

Abstract

Objectives: HIV-1/hepatitis C virus (HCV) coinfection accelerates the progression of liver disease to cirrhosis, particularly in individuals with low CD4 T-cell counts. Highly active antiretroviral therapy (HAART) can significantly increase HCV-specific T-cell responses; however, it remains unclear whether the restoration of HCV-specific T cells by HAART is associated with liver injury in these coinfection patients.

Methods: A total of 32 HIV-1/HCV coinfected patients and 14 HCV monoinfected patients were enrolled, and 13 coinfected patients were initialized HAART and followed up for 6 months. HCV-specific interferon-γ responses to HCV core and NS3A proteins were examined by enzyme-linked immunosorbent spot.

Results: HCV-specific interferon-γ responses to HCV core and NS3A proteins were impaired in HIV-1/HCV-coinfected patients as compared with those in HCV monoinfected patients. The impaired HCV-specific T-cell responses could be efficiently restored during the early phase of HAART, independent of HCV status, and were positively associated with increased CD4 T-cell counts. In addition, this recovery of HCV-specific T-cell responses occurred simultaneously with elevated serum alanine aminotransferase levels in HCV viremic patients and in patients with HCV rebound, but not in HCV nonviremic patients after 6 months of HAART.

Conclusions: The recovery of HCV-specific T-cell responses by HAART may lead to transient liver injury in patients with HIV-1/HCV coinfection, suggesting that early anti-HCV therapy before HAART may reduce the risk of liver injury and therefore may be beneficial to HIV-1/HCV-coinfected patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alanine Transaminase / blood
  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Antiviral Agents / therapeutic use
  • CD4 Lymphocyte Count
  • Coinfection
  • Female
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV-1*
  • Hepacivirus / immunology*
  • Hepatitis C / blood
  • Hepatitis C / drug therapy
  • Hepatitis C / immunology*
  • Hepatitis C Antigens / immunology
  • Humans
  • Interferon-gamma / therapeutic use
  • Liver / immunology*
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Statistics, Nonparametric
  • T-Lymphocytes / immunology*
  • Viral Core Proteins / immunology
  • Viral Load
  • Young Adult

Substances

  • Anti-Retroviral Agents
  • Antiviral Agents
  • Hepatitis C Antigens
  • RNA, Viral
  • Viral Core Proteins
  • Interferon-gamma
  • Alanine Transaminase