IL28B SNP rs8099917 Is Strongly Associated with Pegylated Interferon-α and Ribavirin Therapy Treatment Failure in HCV/HIV-1 Coinfected Patients
Aparicio Prats, Ester (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Parera, Mariona (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Franco Cirera, Sandra (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Pérez-Álvarez, Núria (Institut Germans Trias i Pujol. Fundació de Lluita Contra la Sida)
Tural, Cristina (Institut Germans Trias i Pujol. Fundació de Lluita Contra la Sida)
Clotet Sala, Bonaventura (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Martínez, Miguel Angel (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Universitat Autònoma de Barcelona. Departament de Medicina

Data:	2010
Resum:	Recent genome-wide association studies report that the SNP rs8099917, located 8. 9 kb upstream of the start codon of IL28B, is associated with both disease chronicity and therapeutic response to pegIFN-α and RBV in patients infected with genotype 1 HCV. To determine the effect of rs8099917 variation on the response of HCV to therapy, we genotyped this variant in a cohort of 160 HCV/HIV-1 coinfected patients in our clinic unit who received combined peg-IFN-α/RBV therapy. The rs8099917 T/G or G/G genotypes were observed in 56 patients (35%). Treatment failure occurred in 80% of G-allele carriers versus 48% of non-carriers (P<0. 0001). This result reveals that the G allele was strongly associated with treatment failure in this patient cohort. Importantly, a highly significant association was found between the G-allele and response to therapy in HCV genotype 1-infected patients (P<0. 0001) but not in HCV genotype 3-infected patients. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated that the rs8099917 TT genotype was a strong predictor of treatment success (5. 83; 1. 26-26. 92; P = 0. 021), independent of baseline plasma HCV-RNA load less than 500 000 IU/ml (4. 85; 1. 18-19. 95; P = 0. 025) and absence of advanced liver fibrosis (5. 24; 1. 20-22. 91; P = 0. 025). These results reveal the high prevalence of the rs8099917 G allele in HCV/HIV-1 coinfected patients as well as its strong association with treatment failure in HCV genotype 1-infected patients. rs8099917 SNP genotyping may be a valid pre-treatment predictor of which patients are likely to respond to treatment in this group of difficult-to-treat HCV/HIV-infected patients.
Ajuts:	Ministerio de Sanidad y Consumo RD06/0006 Ministerio de Ciencia e Innovación PI07/0098
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	PloS one, Vol. 5 (october 2010) , ISSN 1932-6203

DOI: 10.1371/journal.pone.0013771
PMID: 21048934

5 p, 127.2 KB

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