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原发性HIV-1感染患者对抗逆转录病毒药物的耐药性。魁北克原发性感染研究的调查人员。

Resistance to antiretroviral drugs in patients with primary HIV-1 infection. Investigators of the Quebec Primary Infection Study.

作者信息

Brenner B, Wainberg M A, Salomon H, Rouleau D, Dascal A, Spira B, Sekaly R P, Conway B, Routy J P

机构信息

McGill University AIDS Centre, Lady Davis Institute-Jewish General Hospital, 3755 Cote Site-Catherine Road, Montreal, Quebec, Canada H3T 1E2.

出版信息

Int J Antimicrob Agents. 2000 Dec;16(4):429-34. doi: 10.1016/s0924-8579(00)00270-3.

Abstract

The widespread use of antiretroviral agents (ARVs) and the growing occurrence of HIV strains resistant to these drugs have given rise to serious concerns regarding the transmission of resistant viruses to newly infected persons. Plasma viral RNA from 80 individuals newly infected between 1997 and 1999 was genotyped by automated sequencing to analyze the profile of viruses resistant to nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs) and to protease inhibitors (PIs). The prevalence of mutations that conferred primary resistance to PIs (L10I, D30Y, V82A, L90M) was 15% of the cohort. RT genotypic variants, associated with high-level resistance to ARVs, were observed in 21% of individuals, including NRTI, NNRTI and multidrug (MDR) resistance in 6, 5, and 10% of cases, respectively. The phenotypic susceptibility of viral isolates to ARVs was also assayed and showed transmission of high-level resistance to ZDV, 3TC, and PIs in those individuals with MDR. The transmission of drug-resistant HIV genotypic variants is a serious problem that merits further attention by public health officials, virologists, and clinicians.

摘要

抗逆转录病毒药物(ARV)的广泛使用以及对这些药物产生耐药性的HIV毒株的不断出现,引发了人们对耐药病毒传播给新感染者的严重担忧。对1997年至1999年间新感染的80个人的血浆病毒RNA进行自动测序基因分型,以分析对核苷类和非核苷类逆转录酶抑制剂(NRTIs和NNRTIs)以及蛋白酶抑制剂(PIs)耐药的病毒谱。对PIs产生原发性耐药的突变(L10I、D30Y、V82A、L90M)的发生率在该队列中为15%。在21%的个体中观察到与对ARV的高水平耐药相关的RT基因变异,其中分别有6%、5%和10%的病例存在对NRTI、NNRTI和多药(MDR)耐药。还检测了病毒分离株对ARV的表型敏感性,结果显示在那些具有MDR的个体中存在对齐多夫定(ZDV)、拉米夫定(3TC)和PIs的高水平耐药的传播。耐药HIV基因变异的传播是一个严重问题,值得公共卫生官员、病毒学家和临床医生进一步关注。

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