Torres-Cornejo A, Ruiz-Valderas R, Jimenez-Jimenez L, Abad-Molina C, Gutierrez-Valencia A, Viciana P, Lopez-Cortes L F
Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
J Viral Hepat. 2014 Mar;21(3):178-88. doi: 10.1111/jvh.12128. Epub 2013 Jul 17.
Studies on the association between the peginterferon-α and ribavirin levels and sustained virological response (SVR) have shown yielded conflicting results, but most of them were performed before the influence of IL28B polymorphisms was known. Our aim was to assess the effects of peginterferon-α 2a and ribavirin plasma levels on viral kinetics and SVR in hepatitis C virus genotype 1 HCV-1/HIV-co-infected patients according to IL28B genotype. This was a cohort study of HCV-1/HIV-co-infected patients who were HCV-treatment naïve and for whom the efficacy of peginterferon-α 2a plus ribavirin was evaluated by per-protocol analysis. The peginterferon-α 2a and ribavirin levels were measured by ELISA and HPLC-UV, respectively. The relationships among host and viral factors, the trough drugs levels and virological responses were analysed by multivariate regression analyses. A total of 131 Caucasian patients were included (cirrhosis:38.9%). Overall, SVR rate was 39.6%. In patients with CC IL28B genotype, SVR was related neither to peginterferon-α 2a nor to ribavirin plasma levels, while higher levels of both drugs were the only variables independently associated with SVR in individuals with CT/TT IL28B genotypes (OR, 5.02; CI95 , 1.45-17.1; P = 0.001 and 4.0; CI95 , 1.08-14.7; P = 0.038, respectively). Moreover, faster viral declines were observed in CT/TT patients when pegIFN-α 2a and ribavirin plasma levels were greater than 3400 pg/mL and 1.6 μg/mL, respectively. In contrast to the results for CC patients, the results in patients carrying the unfavourable CT/TT IL28B genotypes showed that plasma levels of both drugs have significant effects on viral kinetics and SVR.
关于聚乙二醇干扰素-α和利巴韦林水平与持续病毒学应答（SVR）之间关联的研究结果相互矛盾，但其中大多数研究是在白细胞介素28B（IL28B）基因多态性的影响被发现之前进行的。我们的目的是根据IL28B基因型，评估聚乙二醇干扰素-α 2a和利巴韦林血浆水平对丙型肝炎病毒1型（HCV-1）/人类免疫缺陷病毒（HIV）合并感染患者病毒动力学和SVR的影响。这是一项对未经HCV治疗的HCV-1/HIV合并感染患者的队列研究，通过符合方案分析评估聚乙二醇干扰素-α 2a加利巴韦林的疗效。聚乙二醇干扰素-α 2a和利巴韦林水平分别通过酶联免疫吸附测定（ELISA）和高效液相色谱-紫外检测法（HPLC-UV）测量。通过多变量回归分析分析宿主和病毒因素、药物谷浓度水平与病毒学应答之间的关系。共纳入131例白种人患者（肝硬化患者占38.9%）。总体而言，SVR率为39.6%。在IL28B基因型为CC的患者中，SVR与聚乙二醇干扰素-α 2a和利巴韦林血浆水平均无关，而在IL28B基因型为CT/TT的个体中，两种药物的较高水平是与SVR独立相关的唯一变量（优势比分别为5.02；95%置信区间，1.45 - 17.1；P = 0.001和4.0；95%置信区间，1.08 - 14.7；P = 0.038）。此外，当聚乙二醇干扰素-α 2a和利巴韦林血浆水平分别大于3400 pg/mL和1.6 μg/mL时，在CT/TT患者中观察到病毒下降更快。与CC患者的结果相反，携带不利的CT/TT IL28B基因型的患者结果表明，两种药物的血浆水平对病毒动力学和SVR均有显著影响。
