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103K/N和184M/V HIV-1耐药群体的动态变化:血浆病毒RNA与CD45RO+T细胞前病毒DNA的相对比较

Dynamics of 103K/N and 184M/V HIV-1 drug resistant populations: relative comparison in plasma virus RNA versus CD45RO+T cell proviral DNA.

作者信息

Jakobsen M R, Tolstrup M, Bertelsen L, Laursen A, Obel N, Ostergaard L, Mohey R

机构信息

Department of Infectious diseases, Aarhus University Hospital, Skejby Sygehus, Brendstrupgaardvej 100, 8200 Aarhus N, Denmark.

出版信息

J Clin Virol. 2007 Jul;39(3):215-21. doi: 10.1016/j.jcv.2007.04.014. Epub 2007 May 30.

Abstract

BACKGROUND

Viral populations defined by 103K/N and 184M/V as linked or single mutations in the HIV-1 reverse transcriptase gene were investigated in plasma samples and compared with previous findings in the CD45RO(+)T cell compartment.

OBJECTIVE

To develop an ARMS assay for plasma virions and to investigate the expression of resistance mutations (103N and 184V) and dynamic interactions between proviral DNA and plasma virions.

STUDY DESIGN

A clinical cross-sectional study, including 11 patients on lamivudine efavirenz and/or nevirapine therapy. The viral populations were determined by an assay based on real-time PCR and amplification refractory mutation system (ARMS).

RESULTS

The 103N and 184V mutations were not detected in patients with stable low viremia. Patients previously exposed to mono or dual therapy often carried minor viral populations of either one or both mutations in plasma. The viral population with linked mutations (103N and 184V) was detected in two patients after more than 2 years of non-NNRTI HAART.

CONCLUSION

The ARMS assay is useful for detecting viral quasi-species containing efavirenz and lamivudine resistant mutations in plasma virions and in proviral DNA. Data suggest an unequal distribution of linked-mutation populations in plasma and CD45RO(+)T cells. Furthermore, the linked 103N-184V mutation may be more fit than the single 184V mutation and this linked population emerges rapidly under inadequate drug pressure.

摘要

背景

对血浆样本中由HIV-1逆转录酶基因中的103K/N和184M/V作为连锁或单一突变所定义的病毒群体进行了研究,并与先前在CD45RO(+)T细胞区室中的发现进行了比较。

目的

开发一种用于血浆病毒体的扩增阻滞突变系统(ARMS)检测方法,并研究耐药突变(103N和184V)的表达以及前病毒DNA与血浆病毒体之间的动态相互作用。

研究设计

一项临床横断面研究,包括11名接受拉米夫定、依非韦伦和/或奈韦拉平治疗的患者。通过基于实时PCR和扩增阻滞突变系统(ARMS)的检测方法来确定病毒群体。

结果

在病毒血症稳定且水平较低的患者中未检测到103N和184V突变。先前接受过单一或双重治疗的患者血浆中常常携带少量的一种或两种突变的病毒群体。在接受非核苷类逆转录酶抑制剂高效抗逆转录病毒治疗(HAART)超过2年的两名患者中检测到了具有连锁突变(103N和184V)的病毒群体。

结论

ARMS检测方法可用于检测血浆病毒体和前病毒DNA中含有对依非韦伦和拉米夫定耐药突变的病毒准种。数据表明连锁突变群体在血浆和CD45RO(+)T细胞中的分布不均。此外,103N-184V连锁突变可能比单一的184V突变更具适应性,并且在药物压力不足的情况下,这种连锁群体迅速出现。

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