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IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy

BACKGROUND: Genetic studies have demonstrated a strong association between single nucleotide polymorphisms (SNPs) at IL28B and response to treatment with peginterferon (PEG) and ribavirin (RBV) in HCV monoinfected persons. We sought to test these associations in a prospective PEG / weight based riba...

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Autores principales: Abu Dayyeh, Barham K., Gupta, Namrata, Sherman, Kenneth E., de Bakker, Paul I. W., Chung, Raymond T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189209/
https://www.ncbi.nlm.nih.gov/pubmed/22003405
http://dx.doi.org/10.1371/journal.pone.0025753
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author Abu Dayyeh, Barham K.
Gupta, Namrata
Sherman, Kenneth E.
de Bakker, Paul I. W.
Chung, Raymond T.
author_facet Abu Dayyeh, Barham K.
Gupta, Namrata
Sherman, Kenneth E.
de Bakker, Paul I. W.
Chung, Raymond T.
author_sort Abu Dayyeh, Barham K.
collection PubMed
description BACKGROUND: Genetic studies have demonstrated a strong association between single nucleotide polymorphisms (SNPs) at IL28B and response to treatment with peginterferon (PEG) and ribavirin (RBV) in HCV monoinfected persons. We sought to test these associations in a prospective PEG / weight based ribavirin (WBR) treatment trial (ACTG A5178) (National Institution of Health registration number NCT00078403) in persons with HCV-HIV coinfection, and to develop a prediction score. METHODS: We selected subjects enrolled in A5178 who completed at least the first 12 weeks of the trial and had DNA available, and genotyped three SNPs at IL28B (rs12979860, rs12980275, rs8099917). We used multivariate logistic regression analysis to evaluate the association between IL28B SNPs and HCV treatment outcomes and to develop the prediction score. RESULTS: 231 HCV/HIV coinfected subjects were included. We observed a strong association between IL28B genotype and response to therapy among those with genotypes 1 or 4 (odds ratio for complete early virologic responses (cEVR) and sustained virologic response (SVR) was 2.98 [1.7–5.3] and 3.4 [1.7–6.9], respectively, for each additional copy of the C allele of rs12979860). Differences in frequency of the responder allele explained some of the discrepancy in HCV treatment outcomes between blacks and whites. A simple pretreatment prediction score that incorporates the IL28B genotype and baseline HCV viral load has a 93% negative predictive value (NPV) for SVR. CONCLUSIONS: IL28B SNPs have an additive allele dose effect in predicting HCV treatment outcomes in HCV/HIV coinfected persons and can be incorporated into a simple pretreatment prediction score that could minimize the risk of exposure to PEG/RBV therapy for persons with unfavorable scores.
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spelling pubmed-31892092011-10-14 IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy Abu Dayyeh, Barham K. Gupta, Namrata Sherman, Kenneth E. de Bakker, Paul I. W. Chung, Raymond T. PLoS One Research Article BACKGROUND: Genetic studies have demonstrated a strong association between single nucleotide polymorphisms (SNPs) at IL28B and response to treatment with peginterferon (PEG) and ribavirin (RBV) in HCV monoinfected persons. We sought to test these associations in a prospective PEG / weight based ribavirin (WBR) treatment trial (ACTG A5178) (National Institution of Health registration number NCT00078403) in persons with HCV-HIV coinfection, and to develop a prediction score. METHODS: We selected subjects enrolled in A5178 who completed at least the first 12 weeks of the trial and had DNA available, and genotyped three SNPs at IL28B (rs12979860, rs12980275, rs8099917). We used multivariate logistic regression analysis to evaluate the association between IL28B SNPs and HCV treatment outcomes and to develop the prediction score. RESULTS: 231 HCV/HIV coinfected subjects were included. We observed a strong association between IL28B genotype and response to therapy among those with genotypes 1 or 4 (odds ratio for complete early virologic responses (cEVR) and sustained virologic response (SVR) was 2.98 [1.7–5.3] and 3.4 [1.7–6.9], respectively, for each additional copy of the C allele of rs12979860). Differences in frequency of the responder allele explained some of the discrepancy in HCV treatment outcomes between blacks and whites. A simple pretreatment prediction score that incorporates the IL28B genotype and baseline HCV viral load has a 93% negative predictive value (NPV) for SVR. CONCLUSIONS: IL28B SNPs have an additive allele dose effect in predicting HCV treatment outcomes in HCV/HIV coinfected persons and can be incorporated into a simple pretreatment prediction score that could minimize the risk of exposure to PEG/RBV therapy for persons with unfavorable scores. Public Library of Science 2011-10-07 /pmc/articles/PMC3189209/ /pubmed/22003405 http://dx.doi.org/10.1371/journal.pone.0025753 Text en Abu Dayyeh et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Abu Dayyeh, Barham K.
Gupta, Namrata
Sherman, Kenneth E.
de Bakker, Paul I. W.
Chung, Raymond T.
IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy
title IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy
title_full IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy
title_fullStr IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy
title_full_unstemmed IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy
title_short IL28B Alleles Exert an Additive Dose Effect When Applied to HCV-HIV Coinfected Persons Undergoing Peginterferon and Ribavirin Therapy
title_sort il28b alleles exert an additive dose effect when applied to hcv-hiv coinfected persons undergoing peginterferon and ribavirin therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3189209/
https://www.ncbi.nlm.nih.gov/pubmed/22003405
http://dx.doi.org/10.1371/journal.pone.0025753
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