Association between IL28B gene polymorphisms and plasma HCV-RNA levels in HIV/HCV-co-infected patients

Infectious Diseases Department, Hospital Carlos III, Madrid, Spain.
AIDS (London, England) (Impact Factor: 5.55). 03/2011; 25(6):761-6. DOI: 10.1097/QAD.0b013e32834488e7
Source: PubMed


IL28B polymorphisms influence both the rate of spontaneous hepatitis C virus (HCV) clearance and response to interferon α (IFNα)-based therapy. This observation has been reproduced in HIV-co-infected individuals. Controversy exists about the impact of IL28B alleles on HCV load.
CoRIS is a nationwide, open cohort of newly diagnosed HIV-1 adults in Spain. In the subset of HCV-co-infected individuals, the relationship between plasma HCV-RNA and IL28B (rs12979860) genotypes was evaluated.
A total of 4670 HIV-1-infected patients had been included in CoRIS up to June 2010. All were naive for IFNα. HCV antibodies were reactive in 895 (19%). Of them, 289 specimens were available and tested positive for plasma HCV-RNA, with median values of 959 900 IU/ml. The rs12979860 genotype distribution in HCV viremic patients was CC 45%, CT 42.2% and TT 12.8%. The median plasma HCV-RNA according to IL28B genotypes was: CC 1 385 000, CT 848 939 and TT 251 189 IU/ml (P = 0.006). The percentage of patients with HCV-RNA more than 600 000 IU/ml was: CC 67.7%, CT 56.6% and TT 35.1% (P = 0.001). In multivariate analysis, IL28B CC/CT genotypes, infection with HCV genotypes 1/4 and prior intravenous drug users were independent predictors of HCV-RNA more than 600 000 IU/ml.
HIV/HCV-co-infected patients with the C allele (CC/CT) at rs12979860 show significantly higher plasma HCV-RNA load than TT carriers. Notably, plasma HCV-RNA levels associated with poorer response to IFNα-based therapy are significantly more frequent in CC/CT than TT carriers. Hypothetically, patients harboring the rs12979860 allele C could display a lower activity of endogenous IFNα, allowing higher HCV replication while keeping an enhanced susceptibility to exogenous IFNα therapy.

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    • "However, when only baseline data are considered, the proportion of co-infected patients increased to 26.8%, a figure comparable to the 25% reported in the study by Rallon et al. [14] in a cohort of 196 co-infected patients. The association between HCV genotype 1 and the IL28B C allele with higher HCV RNA values is described in HIV-HCV-co-infected patients [11,15]; these findings demonstrated that no unintended selection bias occurred. "
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    ABSTRACT: Background HCV RNA viral load is an important predictor of sustained virological response and, recently, a significant correlation with liver fibrosis was described. We investigated on possible influence of clinical and viro-immunological variables on HCV viral load in HIV-HCV co-infected patients over a study time of three years (2009-2012). Methods We retrospectively enrolled 98 adult patients with a diagnosis of chronic HIV infection in 2009, a diagnosis of chronic HCV infection with a detectable plasma HCV RNA in 2009 and 2012, HCV therapy-naïve or with failed and stopped antiviral treatment before June 2008. The following variables were recorded: age, gender, HCV genotype, IL28B rs12979860 CC genotype, HCV treatment status, advanced liver fibrosis diagnosis, antiretroviral therapy, CD4+ cell count, HCV viral load, HIV RNA (plasma HIV-1 RNA levels were measured from blood samples every three months at least). The correlation was established using linear regression analysis, analysis of variance and Fisher’s exact test. Comparisons between groups were performed using Fisher’s exact test, the independent samples t-test and the t-test for paired data, as appropriate, for continuous variables. A mixed mode (ME) maximum likelihood linear regression model was constructed to evaluate the dependence of HCV viral load. Results HCV RNA levels did not change significantly from 2009 to 2012 (from 3924650 ± 5320177 IU/ml to 3085128 ± 3372347 IU/ml, p = 0.13); the CD4+ count increased significantly (from a mean of 576 to a mean of 654, p = 0.003). Using linear regression, a positive correlation was observed for HCV load and genotype 1 (p = 0.002), nonresponder status (p = 0.04) and with interleukin 28B CC allele (p = 0.05). Other studied covariates failed to reach a significant correlation. Conclusions The HCV RNA load, a known pretreatment predictor of response to antiviral therapy, was independent of the two main parameters of HIV disease, plasma HIV RNA and CD4 cell count, over an observation time of 3 years in patients with recovered or spontaneously maintained immunocompetence.
    AIDS Research and Therapy 02/2014; 11(1):21. DOI:10.1186/1742-6405-11-21 · 1.46 Impact Factor
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    • "To our knowledge, the extent of fluctuations in HCV-RNA in patients with chronic hepatitis C has not been examined longitudinally over long periods in the absence of antiviral therapy using real-time PCR tests. Moreover, the determinants of significant changes in HCV-RNA are unknown, although viral load increases have been reported in patients treated with corticosteroids [13], harboring non-favorable IL28B alleles [14] or with HIV coinfection [15] "
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    ABSTRACT: The concentration of circulating viral RNA at baseline and during antiviral therapy predicts response in both HIV infection and chronic hepatitis C. Retrospective review of longitudinal plasma HCV-RNA determinations in untreated chronic hepatitis C patients. As comparison, longitudinal plasma HIV-RNA measurements were performed in untreated HIV individuals. A total of 3169 HCV-RNA determinations over 43.0±31.6 months were available for 818 chronic hepatitis C patients. For 333 HIV individuals, 1998 HIV-RNA measurements were examined over 27.3±17.5 months. Overall 44% consecutive specimens had >0.5 log variation in HCV-RNA values compared to 23% for HIV-RNA (p<0.001). These rates were 15% and 4%, respectively, for variations >1 log (p<0.001). In multivariate analysis (odds ratio, 95% confidence interval, p), the likelihood of experiencing HCV-RNA variations >0.5 log IU/mL was greater in patients with lower HCV-RNA (0.35 per log[0.26-0.47], 0.001), HIV coinfection (2.57[91.56-4.23], <0.001) and IL28B-CC (1.87[1.28-2.74], 0.001). Fluctuation in circulating HCV-RNA may be clinically meaningful in a substantial proportion of chronic hepatitis C patients. It may influence the best time to prescribe antiviral therapy. Moreover, decisions based on early viral kinetics, such as early stopping rules, may require testing of baseline specimens the closest to treatment initiation.
    Journal of clinical virology: the official publication of the Pan American Society for Clinical Virology 07/2013; 58(2). DOI:10.1016/j.jcv.2013.06.031 · 3.02 Impact Factor
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    • "Furthermore no influence of IL28B polymorphisms (rs12979860) on the outcome of hepatitis B virus infection has been also demonstrated (Martin et al., 2010). Because controversy exists about the impact of rs12979860 and rs8099917 IL28B SNPs on HCV load (Del Campo et al., 2010; Labarga et al., 2011; Thompson et al., 2010), it was examined whether IL28B SNPs affects RSV load. A TaqMan-based real-time PCR technique for RSV RNA quantification was performed on all NPW specimens with positive RT-PCR results for RSV as previously described (Scagnolari et al., 2009). "
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    ABSTRACT: The genetic diversity of the host is believed to be the key of the diversity in the clinical presentation of bronchiolitis. The aim of this study was to determine whether the known rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in interleukin (IL)28B region, influence clinical features and natural history of bronchiolitis. Both SNPs showed no significant association with the risk of hospitalization for respiratory syncytial virus (RSV), viral load, disease severity, and other clinical features of patients. Interestingly infants carrying IL28B rs12979860 TT genotype had lower age at hospital admission than that of infants carrying CC/CT genotypes. Overall our results indicate that both IL28B SNPs had no impact on the clinical course of bronchiolitis with the only exception of the IL28B rs12979860 SNP which increased the risk of hospitalization for bronchiolitis at early age.
    Virus Research 02/2012; 165(2):236-40. DOI:10.1016/j.virusres.2012.02.018 · 2.32 Impact Factor
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