Different impact of IL28B polymorphisms on response to peginterferon-α plus ribavirin in HIV-positive patients infected with HCV subtypes 1a or 1b.
BACKGROUND
HCV subtype 1a has emerged as a predictor of poor response to triple hepatitis C therapy including boceprevir or telaprevir, which largely has been attributed to a lower resistance barrier in HCV-1a compared to -1b.


OBJECTIVE
We examined whether a lower efficacy of pegIFN/RBV on HCV-1a than HCV-1b could alternatively contribute to explain it.


METHODS
All chronic hepatitis C patients who had completed a course of pegIFN/RBV therapy at our institution were examined. For this study we selected individuals that were IFN-naïve and had been successfully subtyped as 1a or 1b. Moreover, only HIV-coinfected patients were included as they represented a more uniform population in terms of demographics and treatment exposure at our institution. The IL28B rs12979860 alleles were typed using the 5' nuclease assay.


RESULTS
A total of 96 individuals were examined, 58 of whom harbored HCV-1a and 38 HCV-1b. IL28B allele distribution was as follows: 33 CC and 63 CT/TT. SVR was achieved by 64% of CC vs 30% of CT/TT patients (p=0.001). On the other hand, SVR was 53% in HCV-1b vs 34% in HCV-1a (p=0.08). Interestingly, the effect of IL28B variants on SVR was mainly recognized in HCV-1a (63% in CC vs 20% in CT/TT; p=0.001), being marginal on HCV-1b (64% in CC vs 46% in CT/TT; p=0.27).


CONCLUSIONS
The rate of SVR to pegIFN/RBV therapy tends to be lower in HIV-infected patients with chronic hepatitis C due to HCV-1a than HCV-1b; being the impact of IL28B variants significantly stronger on HCV-1a than HCV-1b.
Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
Eugenia
E
Vispo
Norma I
NI
Rallon
Pablo
P
Labarga
Pablo
P
Barreiro
Jose Miguel
JM
Benito
Vincent
V
Soriano
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D015331:Cohort Studies; D060085:Coinfection / Q000235:genetics / Q000276:immunology / Q000821:virology; D005260:Female; D006678:HIV / Q000302:isolation & purification; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D000095022:Interferon Lambda
D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C100416:peginterferon alfa-2a