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巴西中西部初治患者中HIV-1 pol基因的系统发育多样性及抗逆转录病毒耐药性突变

HIV-1 pol phylogenetic diversity and antiretroviral resistance mutations in treatment naïve patients from Central West Brazil.

作者信息

Cardoso Ludimila Paula Vaz, Queiroz Boaventura Braz de, Stefani Mariane Martins de Araújo

机构信息

Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiânia/Goiás, Brazil.

出版信息

J Clin Virol. 2009 Oct;46(2):134-9. doi: 10.1016/j.jcv.2009.07.009. Epub 2009 Aug 13.

Abstract

BACKGROUND

Primary resistance represents a challenge for the control of HIV-1 because it can reduce the efficacy of first line antiretroviral therapy and may impact clinical outcomes.

OBJECTIVES

To describe the prevalence of primary HIV-1 drug resistance and subtypes circulating in Central West Brazil.

STUDY DESIGN

103 antiretroviral naïve patients were recruited in Goiânia city, Central West Brazil during 2007-2008. Protease and partial reverse transcriptase regions were retrotranscribed from plasma HIV-1 RNA and 97 were sequenced after direct nested PCR. HIV-1 subtype was assigned by phylogenetic analysis. Primary drug resistance was analyzed by the Calibrated Population Resistance (CPR) tool using Stanford Surveillance Drug Resistance Mutation (SDRM) and International AIDS Society-USA (IAS-USA) major mutation list.

RESULTS

Primary drug resistance mutations ranged from 8% (IAS) to 10% (SDRM). High level resistance to at least one antiretroviral drug was observed. T215D/S revertant mutations were identified in 4/97 patients. HIV-1 subtype B represented 82.5%, subtype F1 6.2%, subtype C 3.1%, B/F1 7.2% and one sample was a F1/C/B mosaic. HIV-1 subtype C sequences formed a monophyletic cluster with other Brazilian subtype C sequences.

CONCLUSIONS

Our HIV-1 pol sequences from Central West region include the first inland HIV-1 subtype C sequences and help compose the molecular epidemiology map of HIV-1 in Brazil. This data also show that a significant proportion of the naïve patients presented important drug resistance mutations. Therefore naive patients from this setting may benefit from pre-treatment genotypic testing to optimize the choice of antiretroviral drugs and to help control HIV-1 transmission.

摘要

背景

原发性耐药是控制HIV-1面临的一项挑战,因为它会降低一线抗逆转录病毒疗法的疗效,并可能影响临床结局。

目的

描述巴西中西部地区原发性HIV-1耐药情况及流行的亚型。

研究设计

2007年至2008年期间,在巴西中西部的戈亚尼亚市招募了103例初治抗逆转录病毒治疗患者。从血浆HIV-1 RNA逆转录蛋白酶和部分逆转录酶区域,97例经直接巢式PCR后进行测序。通过系统发育分析确定HIV-1亚型。使用斯坦福监测耐药突变(SDRM)和美国国际艾滋病协会(IAS-USA)主要突变列表,通过校准群体耐药性(CPR)工具分析原发性耐药。

结果

原发性耐药突变率在8%(IAS)至10%(SDRM)之间。观察到对至少一种抗逆转录病毒药物的高水平耐药。在4/97例患者中鉴定出T215D/S回复突变。HIV-1 B亚型占82.5%,F1亚型占6.2%,C亚型占3.1%,B/F1亚型占7.2%,一个样本为F1/C/B嵌合体。HIV-1 C亚型序列与其他巴西C亚型序列形成一个单系簇。

结论

我们来自中西部地区的HIV-1 pol序列包括首批内陆HIV-1 C亚型序列,有助于构建巴西HIV-1的分子流行病学图谱。这些数据还表明,相当一部分初治患者存在重要的耐药突变。因此,来自该地区的初治患者可能受益于治疗前基因检测,以优化抗逆转录病毒药物的选择并有助于控制HIV-1传播。

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