IL28B gene polymorphisms and viral kinetics in HIV/hepatitis C virus-coinfected patients treated with pegylated interferon and ribavirin.
IL28B gene polymorphisms and viral kinetics in HIV/hepatitis C virus-coinfected patients treated with pegylated interferon and ribavirin.
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DOI：
10.1097/qad.0b013e3283471cae
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发表时间：
2011-05-15
期刊：
影响因子：
--
通讯作者：
Benito JM
中科院分区：
文献类型：
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作者：
Rallón NI;Soriano V;Naggie S;Restrepo C;Goldstein D;Vispo E;McHutchison J;Benito JM
IL 28 B基因上游的单核苷酸多态性（rs 12979860）预测慢性丙型肝炎患者对聚乙二醇干扰素-利巴韦林治疗的持续病毒学应答（SVR）关于这种IL 28 B SNP对治疗期间早期病毒动力学的影响的信息很少，特别是在合并感染HIV的患者中，其治疗反应低于丙型肝炎病毒（HCV）单感染患者。我们选择了196名HIV/HCV合并感染者，他们已经完成了聚乙二醇干扰素-利巴韦林治疗的疗程，并且SVR的结果得到了验证。在单变量和多变量分析中评估IL 28 B SNP与快速、早期和治疗结束病毒学应答[分别为快速病毒学应答（RVR）、早期病毒学应答（EVR）和治疗结束病毒学应答]的关联。研究人群的SVR率为54%。IL 28 B CC基因型频率为44%。HCV基因型分布：HCV-1型占57%，HCV-2型占1%，HCV-3型占30%，HCV-4型占12%。与CT/TT相比，CC基因型与所有治疗中病毒结局的发生率显著更高相关，在调整了其他病毒应答预测因子（如血清HCV-RNA、HCV基因型和肝纤维化分期）后。IL 28 B CC基因型对未达到RVR或cEVR的患者的SVR具有预测能力。IL 28 B SNP与病毒动力学和治疗结果之间的关联仅对HCV基因型1和4具有显著性。IL 28 B CC基因型是HIV/HCV合并感染患者对治疗的病毒学应答的强预测因子这种作用是通过在治疗的前12周内增加病毒清除介导的，主要见于感染HCV基因型1和4的患者。
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. 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. 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. 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.