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莫桑比克马普托1型艾滋病毒整合酶分离株的遗传多样性和自然多态性:对整合酶抑制剂的影响

Genetic diversity and naturally polymorphisms in HIV type 1 integrase isolates from Maputo, Mozambique: implications for integrase inhibitors.

作者信息

Oliveira Michelli F, Ramalho Dulce B, Abreu Celina M, Vubil Adolfo, Mabunda Nédio, Ismael Nalia, Francisco Cidia, Jani Ilesh V, Tanuri Amilcar

机构信息

Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

AIDS Res Hum Retroviruses. 2012 Dec;28(12):1788-92. doi: 10.1089/aid.2012.0058. Epub 2012 May 8.

Abstract

HIV proviral DNA integration into the host chromosome is carried out by integrase becoming an important target antiretroviral therapy. Raltegravir was the first integrase inhibitor approved for use in HIV therapy and elvitegravir is in the late phase of clinical development; both show good results in monotherapy studies and may be used worldwide for rescue therapy. In this work we analyzed 57 integrase sequences obtained from samples from drug-naive and first line regime-failing patients from Maputo, Mozambique, to evaluate the presence of natural polymorphisms and resistance mutations associated with raltegravir and elvitegravir. No major mutations conferring resistance to integrase inhibitors were found and polymorphic accessory mutations were solely observed in low frequency among subtype C sequences-L74M (3.4%), T97A (1.8%), and E157Q (1.8%)-suggesting that this new antiretroviral drug class will be effective in Mozambique providing a good perspective to the introduction of this class of drugs in that country.

摘要

人类免疫缺陷病毒(HIV)前病毒DNA整合到宿主染色体是由整合酶完成的,这使其成为抗逆转录病毒疗法的一个重要靶点。雷特格韦是首个被批准用于HIV治疗的整合酶抑制剂,埃替格韦正处于临床开发后期;二者在单药治疗研究中均显示出良好效果,且可在全球范围内用于挽救治疗。在这项研究中,我们分析了从莫桑比克马普托未接受过治疗和一线治疗失败患者的样本中获得的57个整合酶序列,以评估与雷特格韦和埃替格韦相关的天然多态性和耐药突变的存在情况。未发现赋予整合酶抑制剂耐药性的主要突变,仅在C亚型序列中低频观察到多态性辅助突变——L74M(3.4%)、T97A(1.8%)和E157Q(1.8%)——这表明这类新型抗逆转录病毒药物在莫桑比克将有效,为该国引入这类药物提供了良好前景。

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