Longitudinal monitoring of 2-long terminal repeat circles in peripheral blood mononuclear cells from patients with chronic HIV-1 infection

Longitudinal monitoring of 2-long terminal repeat circles in peripheral blood mononuclear cells from patients with chronic HIV-1 infection
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DOI:
10.1097/00002030-200303280-00001
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发表时间:
2003-03-28
期刊:
影响因子:
3.8
通讯作者:
Leibowitch, J
Leibowitch, J
中科院分区:
医学2区
文献类型:
--
作者:
Brussel, A;Mathez, D;Leibowitch, J

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目的:为了评估2长末端重复序列(LTR)HIV环状DNA定量用于监测治疗的HIV-1感染患者中正在进行的病毒复制的潜在用途。设计和方法:在纵向环境中,HIV-1感染的自然过程在大多数情况下被连续或不连续的抗病毒治疗破坏,采用实时荧光定量PCR技术,对16例慢性HIV-1感染患者外周血单个核细胞样本中HIV-1 DNA的2-LTR环进行定量。我们比较了2-LTR循环水平的变化与血浆病毒RNA水平的伴随变化,并与患者外周血单核细胞中的生产性感染细胞和染色体相关前病毒DNA拷贝数的频率:抗病毒治疗导致血浆病毒血症和感染细胞频率急剧下降。相比之下,我们发现,前病毒DNA和2-LTR环的水平显着较低的治疗下,只有当组的标本是同质的,血浆病毒血症和感染细胞的频率进行了比较。此外,在无法检测到的血浆病毒血症的时间,几乎没有任何下降前病毒DNA或2-LTR循环水平observed.Conclusions:抗病毒治疗对2-LTR循环水平在体内的低影响,当血浆病毒血症和感染细胞的频率都显着下降导致LIS的结论是,2-LTR循环不应该被用于监测最近的病毒复制治疗的患者。(C)2003年利平科特威廉姆斯威尔金斯。
Objective: To evaluate the potential use of 2-long terminal repeats (LTR) HIV circular DNA quantification for the monitoring of ongoing virus replication in treated HIV-1 infected patients.Design and methods: In a longitudinal setting, where the natural course of HIV-1 infection was in most cases disrupted by continuous or discontinuous antiviral therapy, 2-LTR-circles of HIV-1 DNA were quantified in serial peripheral blood mononuclear cell samples, selected in retrospect from 16 patients with chronic HIV-1 infection, using quantitative real-time PCR. We compared variations of 2-LTR circle level with concomitant variations in plasma viral RNA level and with the frequency of productively infected cells and chromosome associated proviral DNA copy numbers in patient's peripheral blood mononuclear cells.Results: Antiviral treatment led to a sharp decrease in plasma viraemia and infectious cell frequency. In contrast, we found that levels of proviral DNA and 2-LTR circles were significantly lower under treatment only when groups of specimens that were homogeneous, with respect both to plasma viraemia and infectious cell frequency, were compared. Moreover, during the time of undetectable plasma viraemia, scarcely any decline in proviral DNA or 2-LTR circle levels was observed.Conclusions: The low impact of antiviral treatment on 2-LTR circle levels in vivo, when plasma viraemia and infectious cell frequency both dramatically decline lead LIS to conclude that 2-LTR circles should not be used for the monitoring of recent viral replication in treated patients. (C) 2003 Lippincott Williams Wilkins.