Evolution of HVR-1 Quasispecies after 1-Year Treatment in HIV/HCV-Coinfected Patients According to the Pattern of Response to Highly Active Antiretroviral Therapy
Evolution of HVR-1 Quasispecies after 1-Year Treatment in HIV/HCV-Coinfected Patients According to the Pattern of Response to Highly Active Antiretroviral Therapy
复制标题
根据高效抗逆转录病毒治疗的反应模式，HIV/HCV 合并感染患者治疗 1 年后 HVR-1 准种的演变
DOI：
10.1177/135965350601100102
复制
发表时间：
2006
影响因子：
1.2
通讯作者：
M. Capobianchi
中科院分区：
文献类型：
--
作者：
M. Solmone;E. Girardi;E. Lalle;I. Abbate;A. Monforte;A. Cozzi;A. Alessandrini;R. Piscopo;F. Ebo;L. Cosco;G. Antonucci;G. Ippolito;M. Capobianchi
丙型肝炎病毒（HCV）的变异主要归因于病毒对宿主免疫压力的反应能力，作为准种进化的驱动力。本研究的目的是研究HIV/HCV合并感染患者中HVR-1异质性的变化和HCV准种的演变，根据高效抗逆转录病毒治疗（HAART）的反应模式。从前瞻性队列研究中选择了16例携带HCV基因型1且接受HAART治疗至少1年的HIV/HCV合并感染患者，其中8例显示CD 4 + T细胞计数增加（免疫应答者），8例显示CD 4 + T细胞计数稳定或减少（免疫无应答者）。HAART治疗1年后，11例患者显示HIV病毒载量<2.6 log 10 cp/ml（病毒学应答者），5例显示HIV病毒载量高于此值（病毒学无应答者）。在开始治疗前和HAART治疗1年后收集的血浆样本进行HCV HVR-1区的克隆序列分析。非同义/同义取代比（Ka/Ks）、氨基酸复杂性（归一化Shannon熵）和多样性（p-距离）被认为是准种异质性的参数。HAART治疗1年后，病毒学无应答者HVR-1准种异质性显著降低，而病毒学应答者异质性倾向于增加。当考虑免疫反应时，进化中的差异不太严格。另一方面，仅在免疫学和病毒学HAART应答患者中观察到HVR-1准种的深刻定性修饰。总的来说，这些研究结果表明，在接受HAART的患者中，HCV变异的程度和HVR-1准种的演变受到抗逆转录病毒治疗反应模式的影响。
Hepatitis C virus (HCV) variability is mainly attributed to the ability of the virus to respond to host immune pressure, acting as a driving force for the evolution of quasispecies. This study was aimed at studying the changes in HVR-1 heterogeneity and the evolution of HCV quasispecies in HIV/HCV-coinfected patients according to the pattern of response to highly active antiretroviral therapy (HAART). Sixteen HIV/HCV-coinfected patients harbouring HCV genotype 1 and who had been on HAART for at least 1 year, 8 showing increasing CD4+T-cell counts (immunological responders) and 8 showing a stable or decreasing CD4+ T-cell counts (immunological non-responders), were selected from a prospective cohort study. After 1 year of HAART, 11 patients showed HIV viral load <2.6 log10 cp/ml (virological responders), and 5 showed HIV viral load above this value (virological non-responders). Plasma samples, collected before starting therapy and after 1 year of HAART, underwent clonal sequence analysis for HVR-1 region of HCV. Non-synonymous/synonymous substitutions ratio (Ka/Ks), aminoacidic complexity (normalized Shannon entropy) and diversity (p-distance), were considered as parameters of quasispecies heterogeneity. After 1 year of HAART, heterogeneity of HVR-1 quasispecies significantly decreased in virological non-responders, whereas the heterogeneity tended to increase in virological responders. The differences in the evolution were less stringent, when considering immunological response. On the other hand, profound qualitative modifications of HVR-1 quasispecies were observed only in patients with both immunological and virological HAART response. On the whole, these findings suggest that, in patients undergoing HAART, the extent of HCV variability and the evolution of HVR-1 quasispecies is influenced by the pattern of response to antiretroviral therapy.
影响因子：
120.7
作者：
Sulkowski, MS;Moore, RD;Thomas, DL
通讯作者：
Thomas, DL
影响因子：
6.4
作者：
Blackard, JT;Yang, YJ;Chung, RT
通讯作者：
Chung, RT