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52例人类免疫缺陷病毒合并感染患者的丙型肝炎病毒基因变异性

Hepatitis C virus genetic variability in 52 human immunodeficiency virus-coinfected patients.

作者信息

Neau Didier, Jouvencel Anne-Christine, Legrand Elisabeth, Trimoulet Pascale, Galperine Tatiana, Chitty Isabelle, Ventura Michel, Le Bail Brigitte, Morlat Philippe, Lacut Jean-Yves, Ragnaud Jean-Marie, Dupon Michel, Fleury Hervé, Lafon Marie-Edith

机构信息

Virology Laboratory, University of Victor Segalen, Bordeaux, France.

出版信息

J Med Virol. 2003 Sep;71(1):41-8. doi: 10.1002/jmv.10451.

Abstract

The aim of this study was to examine whether hepatitis C virus (HCV) pretreatment quasispecies complexity was linked to virological response or other clinical and biological parameters, in human immunodeficiency virus (HIV)-coinfected patients undergoing anti-HCV treatment. In addition, HCV quasispecies composition is described longitudinally in these patients before, during, and after treatment. The 52 HIV-coinfected patients were included in a randomized therapeutic trial. At inclusion, they had CD4(+) counts of >250/micro l, HIV plasma load of <10,000 copies/ml, and chronic HCV infection with genotype 1 (n = 27), 2 (n = 2) or 3 (n = 23). These values were compared at baseline with 32 HCV-only-infected, interferon-naive patients who were infected with genotype 1, 2, or 3 (n = 16, 1, or 15, respectively). HCV complexity was studied by single-strand conformation polymorphism (SSCP) in E2 hypervariable region 1 (HVR1), and diversity was evaluated at inclusion in 20 coinfected patients by sequencing four major SSCP bands. The baseline number of SSCP bands was identical in HIV-infected and control patients. In HIV-infected patients, HCV complexity was not predictive of sustained virological response to anti-HCV treatment and was unrelated to epidemiological factors, immunological parameters linked to HIV infection (CD4(+) counts, T CD4(+) proliferative responses to HIV-1 p24), protease inhibitor treatment, HCV plasma load, or genotype. HCV diversity was lower in genotype 2- and 3-infected patients. Six months after completion of the anti-HCV treatment, in comparison with baseline, SSCP profiles were modified in 13 of the 21 nonresponding coinfected patients with analyzable samples. In conclusion, in HIV-infected patients, HCV variability had no significant influence on virological response to anti-HCV treatment.

摘要

本研究的目的是,在接受抗丙型肝炎病毒(HCV)治疗的人类免疫缺陷病毒(HIV)合并感染患者中,检测HCV治疗前准种复杂性是否与病毒学应答或其他临床及生物学参数相关。此外,还对这些患者治疗前、治疗期间及治疗后的HCV准种组成进行了纵向描述。52例HIV合并感染患者被纳入一项随机治疗试验。纳入时,他们的CD4(+)细胞计数>250/μl,HIV血浆载量<10,000拷贝/ml,且为1型(n = 27)、2型(n = 2)或3型(n = 23)慢性HCV感染。将这些值在基线时与32例仅感染HCV、未接受过干扰素治疗的患者进行比较,这些患者分别感染1型、2型或3型HCV(分别为n = 16、1或15)。通过单链构象多态性(SSCP)研究E2高变区1(HVR1)的HCV复杂性,并通过对20例合并感染患者的4条主要SSCP条带进行测序来评估多样性。HIV感染患者和对照患者的基线SSCP条带数量相同。在HIV感染患者中,HCV复杂性不能预测抗HCV治疗的持续病毒学应答,且与流行病学因素、与HIV感染相关的免疫学参数(CD4(+)细胞计数、T CD4(+)细胞对HIV-1 p24的增殖反应)、蛋白酶抑制剂治疗、HCV血浆载量或基因型无关。2型和3型感染患者的HCV多样性较低。抗HCV治疗结束6个月后,与基线相比,21例无应答合并感染患者中有13例(样本可分析)的SSCP图谱发生了改变。总之,在HIV感染患者中,HCV变异性对抗HCV治疗的病毒学应答无显著影响。

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