de Mendoza Carmen, Martin-Carbonero Luz, Barreiro Pablo, de Baar Michel, Zahonero Natalia, Rodriguez-Novoa Sonia, Benito José Miguel, González-Lahoz Juan, Soriano Vincent
Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
AIDS. 2007 Mar 12;21(5):583-8. doi: 10.1097/QAD.0b013e32805e8742.
The metabolic stress derived from high levels of virus replication in both HIV and hepatitis C virus (HCV) infections results in mitochondrial DNA depletion, which seems to be enhanced in co-infected patients. The use of nucleoside analogues to treat HIV infection may further increase mtDNA depletion by inhibiting gamma DNA polymerase. Information on the impact of therapy with pegylated interferon (pegIFN) plus ribavirin on mtDNA is scarce and conflicting results have been reported.
Fifty-nine HCV/HIV-co-infected patients (43 on and 16 off antiretroviral therapy) who initiated treatment with pegIFN plus ribavirin were retrospectively analysed. The amount of mtDNA in peripheral blood mononuclear cells (PBMC) was measured at baseline and at the end of HCV therapy.
Mean baseline serum HCV-RNA was 5.8 log IU/ml and 56% of patients were infected by HCV genotype 1. An inverse correlation between serum HCV-RNA levels and PBMC mtDNA content was recognized at baseline (r = -0.370; P = 0.006). HCV-RNA suppression at the end of HCV therapy was associated with a significant increase in mtDNA, particularly in patients with baseline HCV-RNA levels greater than 6 log IU/ml (+61 mtDNA copies/cell) and in subjects not taking antiretroviral therapy (+133 mtDNA copies/cell).
HCV replication correlates with the extent of mtDNA depletion in PBMC, and treatment of chronic hepatitis C is associated with a significant improvement in mtDNA content. This benefit, however, is not recognized when HCV medications are used along with antiretroviral therapy, probably because of a deleterious interaction of these drugs on mitochondria.
在HIV和丙型肝炎病毒（HCV）感染中，高水平病毒复制产生的代谢应激会导致线粒体DNA耗竭，在合并感染患者中这种情况似乎更为严重。使用核苷类似物治疗HIV感染可能会通过抑制γ-DNA聚合酶进一步加剧线粒体DNA耗竭。关于聚乙二醇化干扰素（pegIFN）联合利巴韦林治疗对线粒体DNA影响的信息较少，且已有相互矛盾的结果报道。
对59例开始接受pegIFN联合利巴韦林治疗的HCV/HIV合并感染患者（43例正在接受抗逆转录病毒治疗，16例未接受）进行回顾性分析。在基线和HCV治疗结束时测量外周血单个核细胞（PBMC）中线粒体DNA的含量。
平均基线血清HCV-RNA为5.8 log IU/ml，56%的患者感染HCV 1型。在基线时，血清HCV-RNA水平与PBMC线粒体DNA含量呈负相关（r = -0.370；P = 0.006）。HCV治疗结束时HCV-RNA的抑制与线粒体DNA的显著增加相关，特别是在基线HCV-RNA水平大于6 log IU/ml的患者中（+61个线粒体DNA拷贝/细胞）以及未接受抗逆转录病毒治疗的患者中（+133个线粒体DNA拷贝/细胞）。
HCV复制与PBMC中线粒体DNA耗竭程度相关，慢性丙型肝炎的治疗与线粒体DNA含量的显著改善相关。然而，当HCV药物与抗逆转录病毒治疗同时使用时，这种益处未被观察到，可能是因为这些药物对线粒体存在有害相互作用。
