Guzmán-Fulgencio M, Rallón N, Berenguer J, Fernández-Rodríguez A, Soriano V, Miralles P, Jiménez-Sousa M A, Restrepo C, López J C, García-Álvarez M, Aldámiz T, Benito J M, Resino S
HIV/Hepatitis Coinfection Unit, Microbiology National Center, Carlos III Health Institute, Majadahonda, Madrid, Spain.
HIV Med. 2014 Aug;15(7):425-30. doi: 10.1111/hiv.12126. Epub 2014 Feb 24.
Mitochondria are multifunctional organelles with a key role in the innate immune response against viral infections. Mitochondrial DNA (mtDNA) haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV-infected patients, and to a delay in the development of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. We performed a study to investigate whether mtDNA haplogroups may be associated with HCV treatment response in HIV/HCV-coinfected patients on pegylated interferon (pegIFN) plus ribavirin (RBV).
We performed a retrospective study in 304 patients who completed a course of HCV therapy. mtDNA polymorphisms were genotyped using Sequenom's MassARRAY platform. The interleukin-28B (IL-28B) polymorphism (rs12980275) was genotyped using the GoldenGate® assay. Sustained virological response (SVR) was defined as an undetectable HCV viral load at week 24 after the end of treatment. The statistical analysis was carried out using on-treatment data.
The SVR rates were 52.6% (160 of 304) for all patients, and 37.8% (46 of 201) for patients with HCV genotype 1 or 4 vs. 81.4% (83 of 102) for patients with HCV genotype 2 or 3 (P < 0.001). No significant associations were found between mtDNA haplogroup and SVR when all patients were included in the analysis and when patients were stratified by HCV genotype (i.e. those with genotypes 1/4 and 2/3 analysed separately) or IL-28B rs12980275 genotype.
European mtDNA haplogroups were not related to HCV treatment response in HIV/HCV-coinfected patients on pegIFN-α/RBV therapy.
线粒体是多功能细胞器，在针对病毒感染的固有免疫反应中起关键作用。线粒体DNA（mtDNA）单倍群与HIV感染患者的艾滋病进展和CD4 T细胞恢复有关，也与HIV/丙型肝炎病毒（HCV）合并感染患者肝纤维化发展的延迟有关。我们开展了一项研究，以调查mtDNA单倍群是否可能与接受聚乙二醇干扰素（pegIFN）加利巴韦林（RBV）治疗的HIV/HCV合并感染患者的HCV治疗反应相关。
我们对304例完成HCV治疗疗程的患者进行了一项回顾性研究。使用Sequenom的MassARRAY平台对mtDNA多态性进行基因分型。使用GoldenGate®检测法对白细胞介素-28B（IL-28B）多态性（rs12980275）进行基因分型。持续病毒学应答（SVR）定义为治疗结束后第24周时检测不到HCV病毒载量。使用治疗期数据进行统计分析。
所有患者的SVR率为52.6%（304例中的160例），HCV基因型1或4的患者为37.8%（201例中的46例），而HCV基因型2或3的患者为81.4%（102例中的83例）（P < 0.001）。当所有患者纳入分析以及按HCV基因型（即分别分析基因型1/4和2/3的患者）或IL-28B rs12980275基因型进行分层时，未发现mtDNA单倍群与SVR之间存在显著关联。
欧洲mtDNA单倍群与接受pegIFN-α/RBV治疗的HIV/HCV合并感染患者的HCV治疗反应无关。
