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印度西部初治和经治抗逆转录病毒治疗个体中整合酶链转移抑制剂相关耐药性的缺失

Absence of Integrase Strand Transfer Inhibitor Associated Resistance in Antiretroviral Therapy Naïve and Experienced Individuals from Western India.

作者信息

Karade Santosh, Sen Sourav, Sashindran Vangal Krishnaswamy

机构信息

1 Department of Microbiology, Armed Forces Medical College, Pune, India.

2 Department of Medicine, Armed Forces Medical College, Pune, India.

出版信息

AIDS Res Hum Retroviruses. 2019 Jun;35(6):567-571. doi: 10.1089/AID.2018.0272. Epub 2019 Apr 8.

Abstract

The Indian national AIDS control program heavily relies on low cost nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI). With global increase in resistance to these, alternative antiretroviral combinations need to be explored. Owing to higher potency, better efficacy and tolerability, recently WHO recommended integrase strand transfer inhibitor (INSTI) based first-line antiretroviral therapy (ART). There is lack of INSTI resistance surveillance data from India. Thus, there is a need to analyze integrase (IN) gene from primarily HIV-1 subtype C infected Indian population, before widespread introduction of INSTI in first-line ART. Plasma samples were collected from INSTI naïve individuals reporting to ART centre of Pune, India. RNA was extracted and IN gene was amplified by nested polymerase chain reaction (PCR) using prior published primers. PCR product of 867 bp was bi-directionally sequenced and resistance associated mutation were analyzed using Stanford University HIV drug resistance algorithm. A total of 58 HIV-1 sequences from 62 INSTI naïve individuals were successfully genotyped. Of these 58, 40 were ART naïve, newly diagnosed and remaining individuals were on NRTI, NNRTI, or protease inhibitors based failing regimen. The commonest subtype identified in the study was C (93%) followed by A1 (3.5%). A total of 191 (66.31%) fully conserved amino acid (aa) positions were observed in IN gene. Overall there was absence of major INSTI resistance mutation, however, E157Q (13.79%) emerged as common polymorphic mutation. Other accessory mutations were L74IM (34.48%), Q95K (1.72%), and T97A (1.72%). To conclude, this first Indian study on primarily HIV-1 subtype C sequences characterized aa variations in IN gene and indicated absence of major INSTI resistance associated mutations.

摘要

印度国家艾滋病控制项目严重依赖低成本的核苷类逆转录酶抑制剂(NRTI)和非核苷类逆转录酶抑制剂(NNRTI)。随着全球对这些药物耐药性的增加,需要探索替代的抗逆转录病毒联合疗法。由于整合酶链转移抑制剂(INSTI)效力更高、疗效和耐受性更好,世界卫生组织最近推荐基于INSTI的一线抗逆转录病毒疗法(ART)。印度缺乏INSTI耐药性监测数据。因此,在一线ART中广泛引入INSTI之前,有必要分析主要感染HIV-1 C亚型的印度人群的整合酶(IN)基因。从印度浦那ART中心报告的未使用过INSTI的个体中采集血浆样本。提取RNA,并使用先前发表的引物通过巢式聚合酶链反应(PCR)扩增IN基因。对867 bp的PCR产物进行双向测序,并使用斯坦福大学HIV耐药性算法分析耐药相关突变。来自62名未使用过INSTI的个体的58个HIV-1序列成功进行了基因分型。在这58个序列中,40个是未接受过ART的新诊断个体,其余个体正在接受基于NRTI、NNRTI或蛋白酶抑制剂的失败治疗方案。研究中鉴定出的最常见亚型是C(93%),其次是A1(3.5%)。在IN基因中总共观察到191个(66.31%)完全保守的氨基酸(aa)位置。总体而言,没有主要的INSTI耐药突变,但E157Q(13.79%)成为常见的多态性突变。其他辅助突变包括L74IM(34.48%)、Q95K(1.72%)和T97A(1.72%)。总之,这项关于主要HIV-1 C亚型序列的首次印度研究对IN基因中的aa变异进行了表征,并表明不存在主要的INSTI耐药相关突变。

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