IL28B SNP rs8099917 is strongly associated with pegylated interferon-α and ribavirin therapy treatment failure in HCV/HIV-1 coinfected patients.
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.
Fundació irsiCaixa, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain.
Ester
E
Aparicio
Mariona
M
Parera
Sandra
S
Franco
Nuria
N
Pérez-Alvarez
Cristina
C
Tural
Bonaventura
B
Clotet
Miguel Angel
MA
Martínez
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D015658:HIV Infections / Q000150:complications*; D015497:HIV-1 / Q000302:isolation & purification; D006526:Hepatitis C / Q000150:complications / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D019562:Viral Load
D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin