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. 2011 May 15;25(8):1025-33.
doi: 10.1097/QAD.0b013e3283471cae.

IL28B gene polymorphisms and viral kinetics in HIV/hepatitis C virus-coinfected patients treated with pegylated interferon and ribavirin

Norma I Rallón  1 , Vincent Soriano, Susanna Naggie, Clara Restrepo, David Goldstein, Eugenia Vispo, John McHutchison, José M Benito
Affiliations

IL28B gene polymorphisms and viral kinetics in HIV/hepatitis C virus-coinfected patients treated with pegylated interferon and ribavirin

Norma I Rallón et al. AIDS. .

Abstract

Background: A single nucleotide polymorphism (SNP) upstream of the IL28B gene (rs12979860) predicts sustained virological response (SVR) to peginterferon-ribavirin therapy in chronic hepatitis C patients. There is scarce information regarding the influence of this IL28B SNP on early viral kinetics during therapy, particularly in patients coinfected with HIV, in whom treatment response is lower than in hepatitis C virus (HCV)-monoinfected patients.

Methods: We selected 196 HIV/HCV-coinfected individuals who had completed a course of peginterferon-ribavirin therapy, and a validated outcome for SVR. Association of IL28B SNPs with rapid, early and end-of-treatment virological responses [rapid virological response (RVR), early virological response (EVR) and end of treatment virological response, respectively] was assessed in univariate and multivariate analyses.

Results: Rate of SVR in the study population was 54%. Frequency of the IL28B CC genotype was 44%. The distribution of HCV genotypes was as follows: HCV-1 57%, HCV-2 1%, HCV-3 30% and HCV-4 12%. Compared to CT/TT, the CC genotype was associated with significantly higher rates of all on-treatment viral outcomes, after adjusting for other predictors of viral response as serum HCV-RNA, HCV genotype and liver fibrosis staging. IL28B CC genotype kept its predictive power of SVR in patients who did not achieve RVR or cEVR. The association between IL28B SNP and viral kinetics and treatment outcomes was significant only for HCV genotypes 1 and 4.

Conclusion: IL28B CC genotype is a strong predictor of virological response to therapy in HIV/HCV-coinfected patients. This effect is mediated by an increase in viral clearance during the first 12 weeks of treatment and is mainly seen in patients infected with HCV genotypes 1 and 4.

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Conflict of interest statement

The authors acknowledge no financial conflict of interest with this work.

Figures

Fig. 1
Fig. 1. Viral kinetics on the basis of IL28B genotype
Viral kinetics on the basis of IL28B genotype in all patients, in patients infected with hepatitis C virus (HCV) genotypes 1 or 4 and in patients infected with HCV genotypes 2 or 3. Data show median (interquartile range) reduction of HCV viral load from baseline to 4 and 12 weeks post-HCV therapy. (*) P < 0.0001 for comparison between non-CC and CC patients using Mann-Whitney nonparametric test.
Fig. 2
Fig. 2. Predictors of virological responses to peginterferon–ribavirin therapy in HIV/HCV-coinfected patients
Horizontal axes represent adjusted odds ratio (95% confidence interval).
See this image and copyright information in PMC

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