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南非东开普省未经治疗的 HIV-1 整合酶基因序列分析。

Analyses of HIV-1 integrase gene sequences among treatment-naive patients in the Eastern Cape, South Africa.

机构信息

South Africa Medical Research Council and Water Quality Monitoring Centre, University of Fort Hare, Alice, Eastern Cape, South Africa.

Applied Environmental and Microbiology Research Group, University of Fort Hare, Alice, Eastern Cape, South Africa.

出版信息

J Med Virol. 2020 Aug;92(8):1165-1172. doi: 10.1002/jmv.25661. Epub 2020 Jan 17.

Abstract

Drug resistance has been recognized in all available therapeutic class of medications for the management of human immunodeficiency virus-1 (HIV-1) infected patients. This makes the continuous study of HIV drug resistance and new treatment options pertinent to patients and researchers globally. The aim of this study is to analyze the complete HIV-1 integrase gene for the possible occurrence of resistance mutations or polymorphisms. We performed genetic analyses on 48 treatment-naive HIV-1-infected patients using nested polymerase chain reaction. Integrase drug-related resistance mutation (DRMs) analysis was performed on all generated sequences according to Stanford HIV drug interpretation program and the International AIDS Society-USA guidelines while phylogenetic analysis was inferred using MEGA 6. The study revealed no major resistance-associated mutation. However, E157Q (2.1%), L74M/I (4.2%), and P142T (2.1%) were the observed accessory and polymorphic mutations. Naturally occurring polymorphism observed were E11D, K14R, D25E, V31I, M50I, V72I, P90T, F100Y, L101I, T124A, T125A, K136Q, D167E, V201I, L234I, A265V, A269K, D278A, and S283G. Phylogenetic analysis delineated all the sequences as HIV-1 subtype C. The study revealed the absence of major integrase inhibitors associated resistance mutations in a setting where integrase inhibitor is administered as salvage therapy in patients developing resistance to first and second-line antiretroviral treatment. However minor and natural polymorphisms were observed and thus may influence the outcome of each treatment regimen. However, additional studies are required to precisely evaluate the impact of these mutations on integrase inhibitors in the Eastern Cape of South Africa.

摘要

所有可用于治疗人类免疫缺陷病毒 1 型(HIV-1)感染患者的治疗类别药物都已被证实存在耐药性。这使得对 HIV 耐药性和新治疗方案的持续研究与全球患者和研究人员息息相关。本研究旨在分析 HIV-1 整合酶基因的全长序列,以发现可能存在的耐药突变或多态性。我们对 48 名未经治疗的 HIV-1 感染患者进行了巢式聚合酶链反应,对所有生成的序列进行了整合酶药物相关耐药突变(DRMs)分析,分析依据是斯坦福 HIV 药物解读程序和国际艾滋病协会-美国指南,而系统进化分析则是使用 MEGA 6 进行推断。研究结果未发现主要的耐药相关突变,但观察到了一些辅助性和多态性突变,包括 E157Q(2.1%)、L74M/I(4.2%)和 P142T(2.1%)。观察到的自然发生的多态性包括 E11D、K14R、D25E、V31I、M50I、V72I、P90T、F100Y、L101I、T124A、T125A、K136Q、D167E、V201I、L234I、A265V、A269K、D278A 和 S283G。系统进化分析将所有序列均划分为 HIV-1 亚型 C。本研究表明,在整合酶抑制剂被用作对一线和二线抗逆转录病毒治疗产生耐药的患者的挽救治疗的情况下,不存在主要的整合酶抑制剂相关耐药突变。然而,观察到了一些次要的和自然的多态性,这可能会影响每种治疗方案的结果。然而,需要进一步的研究来准确评估这些突变对南非东开普省的整合酶抑制剂的影响。

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