title: HCV-specific T-cell responses in HIV/hepatitis C virus-coinfected patients on highly active antiretroviral therapy are comparable to those observed in hepatitis C virus-monoinfected individuals.
abstract: BACKGROUND
  Cellular responses against hepatitis C virus (HCV) are impaired in HIV/HCV-coinfected patients showing uncontrolled viral replication and immune suppression. Very few studies have explored to what extent HCV-specific response improves as a consequence of control of HIV replication by highly active antiretroviral therapy. We compared HCV-specific T-cell responses between HIV/HCV-coinfected patients, showing complete viral suppression, and HCV-monoinfected patients.
  
  
  METHODS
  HCV-specific T-cell responses were examined in 50 interferon-naive patients with chronic hepatitis C: 27 HCV-mono-infected and 23 HIV/HCV-coinfected on highly active antiretroviral therapy and undetectable HIV load. Production of interferon-γ and tumor necrosis factor-α was simultaneously measured in response to genotype-matched overlapping peptides spanning the whole HCV proteome by flow cytometry. Differences between groups were tested using nonparametric tests.
  
  
  RESULTS
  More than half of patients presented CD4+ (60%) or CD8+ (57%) response to at least one HCV protein with no significant differences between both groups. Intensity and breadth of response were also similar between groups. The functional profile of response was represented, in both groups, mainly by monofunctional subsets, although there were some differences between CD4+ and CD8+ T-cell response. CD8+ response was mediated almost exclusively by monofunctional interferon-γ+ cells, whereas bifunctional interferon-γ+ tumor necrosis factor-α+ cells showed a moderate contribution to CD4+ response. Most of the CD8+ response was mediated by interferon-γ, whereas tumor necrosis factor-α was the highest contributor to CD4+ response.
  
  
  CONCLUSIONS
  Our study demonstrates that in HIV/HCV-coinfected patients with maximal HIV suppression under highly active antiretroviral therapy, several characteristics of anti-HCV T-cell response are similar to those found in HCV-monoinfected patients, suggesting that control of HIV replication might improve HCV-specific T-cell response in HIV/HCV-coinfected patients.
authors.affiliation: Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
authors.forename: Norma I
authors.initials: NI
authors.lastname: Rallón
authors.forename: Vincent
authors.initials: V
authors.lastname: Soriano
authors.forename: Clara
authors.initials: C
authors.lastname: Restrepo
authors.forename: Javier
authors.initials: J
authors.lastname: García-Samaniego
authors.forename: Pablo
authors.initials: P
authors.lastname: Labarga
authors.forename: Mariola
authors.initials: M
authors.lastname: López
authors.forename: Alejandra
authors.initials: A
authors.lastname: Peris
authors.forename: Juan
authors.initials: J
authors.lastname: González-Lahoz
authors.forename: José M
authors.initials: JM
authors.lastname: Benito
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology; D003430:Cross-Sectional Studies; D005434:Flow Cytometry; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D008875:Middle Aged; D012367:RNA, Viral / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000276:immunology; D019562:Viral Load / Q000276:immunology
chemical_list: D012367:RNA, Viral; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma