CXCL9, CXCL10 and CXCL11 polymorphisms are associated with sustained virologic response in HIV/HCV-coinfected

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Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3
11:10

Genotypic Inference of HIV-1 Tropism Using Population-based Sequencing of V3

Published on: December 27, 2010

13.2K

Daniel Pineda-Tenor1, Juan Berenguer2, María A Jiménez-Sousa1

  • 1Unidad de Infección Viral e Inmunidad, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid, Spain.

Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology
|September 15, 2014
PubMed

Insights

Certain CXCL9-11 gene variants are linked to higher sustained virological response (SVR) rates in HIV/HCV-coinfected patients receiving pegylated-interferon-alpha plus ribavirin therapy. These findings may guide personalized treatment strategies for hepatitis C virus clearance.

Area of Science:

  • Immunology
  • Virology
  • Genetics

Background:

  • Chemokines CXCL9, CXCL10, and CXCL11 (CXCL9-11) are crucial for hepatitis C virus (HCV) eradication.
  • HCV-specific immunity often fails, leading to chronic hepatitis C.
  • Understanding genetic factors influencing treatment response is vital.

Purpose of the Study:

  • To investigate the association between CXCL9-11 gene polymorphisms and sustained virological response (SVR) in HIV/HCV-coinfected patients.
  • To evaluate treatment outcomes with pegylated-interferon-alpha plus ribavirin based on specific chemokine gene variants.
  • To identify genetic markers that predict successful HCV therapy.

Main Methods:

  • Retrospective study of 176 treatment-naïve HIV/HCV-coinfected patients.
  • Genotyping of CXCL9 (rs10336), CXCL10 (rs3921), and CXCL11 (rs4619915) polymorphisms using GoldenGate® assay.
  • Analysis of genetic data under a recessive inheritance model, defining SVR as undetectable HCV viremia at 24 weeks post-treatment.

Main Results:

  • In HCV genotype 1/4 (GT1/4) patients, carriage of rs10336 TT, rs3921 GG, and rs4619915 AA genotypes was associated with higher SVR rates and increased likelihood of achieving SVR.
  • The TGA haplotype (favorable alleles) showed significantly better odds of achieving SVR compared to the CCG haplotype (unfavorable alleles) in GT1/4 patients (OR=2.69; p=0.003).
  • No significant associations were observed in GT2/3 patients; similar results were found in on-treatment analyses.

Conclusions:

  • Homozygosity for the minor allele of CXCL9 rs10336, CXCL10 rs3921, and CXCL11 rs4619915 is linked to a higher likelihood of HCV clearance.
  • These findings are specific to HIV-infected patients coinfected with HCV GT1/4 undergoing pegIFNα/ribavirin therapy.
  • Genetic profiling of these chemokine polymorphisms may help predict treatment success in specific patient populations.
Abstract

Keywords:
CXCLChronic hepatitis CHCV therapyHIV/AIDSSNPs

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