title: HIV-1 tropism and liver fibrosis in HIV-HCV co-infected patients.
abstract: OBJECTIVE
  Hepatic stellate cells, the major producers of extracellular matrix in the liver, and hepatocytes bear CXCR4 and CCR5, the two main co-receptors for entry of the human immunodeficiency virus (HIV). In vitro studies suggest that HIV-envelope proteins can modulate the replication of hepatitis C virus (HCV) and fibrogenesis. We investigated the influence of HIV tropism on liver fibrosis and the concentration of HCV RNA in HIV-HCV co-infected patients.
  
  
  METHODS
  We used a phenotypic assay to assess HIV tropism in 172 HCV-HIV co-infected patients: one group (75 patients) had mild fibrosis (score ≤F2) and the other (97 patients) had severe fibrosis (score >F2). We also assessed the relationship between HIV tropism and HCV RNA concentration in all these patients. We also followed 34 of these patients for 3 years to determine the evolution of HIV tropism and liver fibrosis, estimated by liver stiffness.
  
  
  RESULTS
  Initially, most patients (91.8%) received a potent antiretroviral therapy. CXCR4-using viruses were found in 29% of patients. The only factor associated with a CXCR4-using virus infection in multivariate analysis was the nadir of CD4 cells: <200/mm(3) (OR: 3.94, 95%CI: 1.39-11.14). The median HCV RNA concentrations in patients infected with R5 viruses, those with dual-mixed viruses and those with X4 viruses, were all similar. The prevalence of CXCR4-using viruses in patients with mild fibrosis (≤F2) (31%) and those with severe fibrosis (F3-F4) (28%, p = 0.6) was similar. Longitudinal analyses showed that the presence of CXCR4-using viruses did not increase the likelihood of fibrosis progression, evaluated by measuring liver stiffness.
  
  
  CONCLUSIONS
  The presence of CXCR4-using viruses in patients receiving a potent antiretroviral therapy does not influence HCV RNA concentration or liver fibrosis.
authors.affiliation: INSERM, U1043, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France. abravanel.f@chu-toulouse.fr
authors.forename: Florence
authors.initials: F
authors.lastname: Abravanel
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Raymond
authors.forename: Elodie
authors.initials: E
authors.lastname: Pambrun
authors.forename: Maria
authors.initials: M
authors.lastname: Winnock
authors.forename: Philippe
authors.initials: P
authors.lastname: Bonnard
authors.forename: Philippe
authors.initials: P
authors.lastname: Sogni
authors.forename: Pascale
authors.initials: P
authors.lastname: Trimoulet
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.forename: Dominique
authors.initials: D
authors.lastname: Salmon-Ceron
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
mesh_terms: D000328:Adult; D000368:Aged; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use; D060085:Coinfection; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000378:metabolism*; D016174:Hepacivirus / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy / Q000473:pathology* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012367:RNA, Viral / Q000096:biosynthesis*; D019713:Receptors, CCR5 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism; D056189:Viral Tropism / Q000502:physiology*
chemical_list: D000998:Antiviral Agents; D012367:RNA, Viral; D019713:Receptors, CCR5; D019718:Receptors, CXCR4