HLA-E variants are associated with sustained virological response in HIV/hepatitis C virus-coinfected patients on hepatitis C virus therapy

AIDS. 2013 May 15;27(8):1231-8. doi: 10.1097/QAD.0b013e32835f5b9c.

Abstract

Objectives: To analyze whether human leukocyte antigen (HLA)-E allelic variants are associated with and may predict response to peg-interferon (IFN) alpha and ribavirin treatment in HIV/hepatitis C virus (HCV)-coinfected patients.

Design: Retrospective follow-up study.

Methods: We studied 321 naive patients who started HCV treatment. HLA-E genotyping was performed by restriction fragment length polymorphism. A sustained virological response (SVR) was defined as undetectable plasma HCV-RNA up through 24 weeks after the end of HCV treatment.

Results: The HLA-E*0101 allele increased the odds of achieving SVR for all patients [adjusted odds ratio (aOR) = 2.03 (95% confidence interval, 95% CI = 1.35-3.06); P = 0.001], for HCV genotype (GT) 1/4 patients (aOR = 1.62 (95% CI = 1.03-2.54), P = 0.035), and for GT2/3 patients [aOR = 9.87 (95% CI = 2.47-31.89), P = 0.001]. For decision tree analysis, the SVR rate increased from 0 to 82.6% and then to 92.5% in GT2/3 patients when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 TT genotype, the SVR rate increased from 33.3 to 54.8% and then to 61.8% when the count of HLA-E*0101 alleles increased. In GT1/4 patients with rs8099917 GT/GG genotype, the SVR rate increased from 15.4 to 22% and then to 44% when the count of HLA-E*0101 alleles increased. The overall percentage of patients correctly classified was 73.2% and the area under the receiver operating characteristic curve (AUROC) was 0.803 ± 0.024.

Conclusion: The HLA-E*0101 allele was associated with increased odds of HCV clearance and could help to predict SVR among HIV/HCV-coinfected patients on HCV therapy. This would be helpful to avoid treatment in those less likely to respond to pegylated-interferon-alpha and ribavirin treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antiviral Agents / therapeutic use*
  • Coinfection
  • Female
  • Follow-Up Studies
  • Genotyping Techniques
  • HIV Infections / drug therapy*
  • HIV Infections / genetics
  • HLA-E Antigens
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide
  • Recombinant Proteins / therapeutic use
  • Retrospective Studies
  • Ribavirin / therapeutic use*
  • Viral Load

Substances

  • Antiviral Agents
  • Histocompatibility Antigens Class I
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2b
  • peginterferon alfa-2a