title: Survival and HLA-B*57 in HIV/HCV Co-Infected Patients on Highly Active Antiretroviral Therapy (HAART).
abstract: OBJECTIVE
  HLA class I alleles, in particular HLA-B*57, constitute the most consistent host factor determining outcomes in untreated HCV- and HIV-infection. In this prospective cohort study, we analysed the impact of HLA class I alleles on all-cause mortality in patients with HIV-, HCV- and HIV/HCV- co-infection receiving HAART.
  
  
  METHODS
  In 2003 HLA-A and B alleles were determined and patients were prospectively followed in 3-month intervals until 2013 or death. HLA-A and B alleles were determined by strand-specific oligonucleotide hybridisation and PCR in 468 Caucasian patients with HCV- (n=120), HIV- (n=186) and HIV/HCV-infection (n=162). All patients with HIV-infection were on HAART. In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis.
  
  
  RESULTS
  At recruitment the proportion of patients carrying a HLA-B*57 allele differed between HIV- (12.9%) and HCV-infection (4.2%). Kaplan Meier analysis revealed significantly increased mortality in HLA-B*57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections. Cox logistic regression analysis confirmed HLA-B*57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients.
  
  
  CONCLUSIONS
  Differences in the prevalence of HLA-B*57 at study entry between HIV- and HCV- infected patients may reflect immune selection in the absence of antiviral therapy. When patients were treated with HAART, however, HLA-B*57 was associated with increased mortality and risk to die from bacterial infections and sepsis, suggesting an ambiguous role of HLA-B*57 for survival in HIV/HCV infection depending on the circumstances.
authors.affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.
authors.forename: Leona
authors.initials: L
authors.lastname: Dold
authors.affiliation: Westmead Clinical School, University of Sydney, Sydney, Australia.
authors.forename: Golo
authors.initials: G
authors.lastname: Ahlenstiel
authors.affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Althausen
authors.affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.
authors.forename: Carolin
authors.initials: C
authors.lastname: Luda
authors.affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.
authors.forename: Carolynne
authors.initials: C
authors.lastname: Schwarze-Zander
authors.affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Boesecke
authors.affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.
authors.forename: Jan-Christian
authors.initials: JC
authors.lastname: Wasmuth
authors.affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.
authors.forename: Jürgen Kurt
authors.initials: JK
authors.lastname: Rockstroh
authors.affiliation: Department of Internal Medicine 1, Rheinische Friedrich-Wilhelms University Bonn, Bonn, Germany; German Centre of Infection Research (DZIF), partner site Cologne-Bonn, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Spengler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D060085:Coinfection / Q000276:immunology / Q000401:mortality*; D018450:Disease Progression; D005500:Follow-Up Studies; D005787:Gene Frequency; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D005838:Genotype; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000401:mortality*; D015234:HLA-A Antigens / Q000032:analysis; D015235:HLA-B Antigens / Q000032:analysis* / Q000235:genetics; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000401:mortality*; D006801:Humans; D006932:Hyperbilirubinemia / Q000209:etiology; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019562:Viral Load; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D019380:Anti-HIV Agents; D015234:HLA-A Antigens; D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D005723:gamma-Glutamyltransferase