de Mendoza Carmen, Sánchez-Conde Matilde, Timmermans Eveline, Buitelaar Marije, de Baar Michel P, Gonzalez-Lahoz Juan, Soriano Vincent
Service of Infectious Diseases, Hospital Carlos III, Madrid, Spain.
Antivir Ther. 2005;10(4):557-61.
Mitochondrial DNA (mtDNA) damage seems to be responsible for many of the toxicities associated with the long-term use of nucleoside analogues in HIV-infected patients. These adverse effects, mainly lipoatrophy, seem to be even more pronounced in subjects with hepatitis C virus (HCV) co-infection. However, there is no information about a possible additive effect of HCV on mtDNA depletion nor about the impact of ribavirin use in HIV/HCV-coinfected individuals.
mtDNA was measured in peripheral blood mononuclear cells (PBMC) collected from 192 individuals classified into 4 groups: HIV-neg/HCV-neg (control group, n = 11), HIV-pos/HCV-neg (56), HIV-neg/HCV-pos (18) and HIV-pos/HCV-pos (107). A duplex real-time NASBA assay was used to quantify mtDNA on maximal platelet-depleted specimens and all experiments were run in duplicate. The mtDNA copy number per cell was estimated taking as reference the nuclear DNA copy number.
The mean mtDNA values in the control group was 757 copies/cell, while it was 428, 349 and 296 for HIV-pos, HCV-pos and HIV/HCV-coinfected individuals, respectively (P < 0.001 for all groups relative to the control group). No significant differences were observed when comparing patients with HIV or HCV infections alone, but coinfected individuals showed a lower mtDNA copy number than patients infected with HIV (P < 0.001) or with HCV (P = 0.089). In a subset of 18 patients with HIV/HCV-coinfection, treatment with pegylated interferon plus ribavirin produced a further reduction in mtDNA (mean value, 189 copies/cell; P = 0.009).
HIV and HCV may independently cause mtDNA depletion in PBMC. Coinfection may result in more pronounced mtDNA depletion. The administration of interferon plus ribavirin may further enhance mtDNA depletion. These findings may explain the greater risk of lipoatrophy of antiretroviral therapy in HIV-infected patients with HCV coinfection and why anti-HCV therapy may aggravate this effect.
线粒体DNA（mtDNA）损伤似乎是导致HIV感染患者长期使用核苷类似物所产生的许多毒性反应的原因。这些不良反应，主要是脂肪萎缩，在丙型肝炎病毒（HCV）合并感染的患者中似乎更为明显。然而，目前尚无关于HCV对mtDNA耗竭可能产生的叠加效应的信息，也没有关于利巴韦林在HIV/HCV合并感染个体中使用的影响的信息。
对192名个体的外周血单个核细胞（PBMC）中的mtDNA进行检测，这些个体分为4组：HIV阴性/HCV阴性（对照组，n = 11）、HIV阳性/HCV阴性（56例）、HIV阴性/HCV阳性（18例）和HIV阳性/HCV阳性（107例）。采用双链实时核酸序列扩增技术（NASBA）对血小板最大程度去除的标本中的mtDNA进行定量，所有实验均重复进行。以核DNA拷贝数为参照估计每个细胞的mtDNA拷贝数。
对照组的平均mtDNA值为757拷贝/细胞，而HIV阳性、HCV阳性和HIV/HCV合并感染个体的该值分别为428、349和296拷贝/细胞（所有组与对照组相比，P < 0.001）。单独比较HIV感染或HCV感染患者时未观察到显著差异，但合并感染个体的mtDNA拷贝数低于HIV感染患者（P < 0.001）或HCV感染患者（P = 0.089）。在18例HIV/HCV合并感染患者的亚组中，聚乙二醇化干扰素联合利巴韦林治疗使mtDNA进一步减少（平均值为189拷贝/细胞；P = 0.009）。
HIV和HCV可能独立导致PBMC中的mtDNA耗竭。合并感染可能导致更明显的mtDNA耗竭。干扰素联合利巴韦林治疗可能会进一步加剧mtDNA耗竭。这些发现可能解释了HCV合并感染的HIV感染患者接受抗逆转录病毒治疗时脂肪萎缩风险更高的原因，以及抗HCV治疗为何会加重这种效应。
