Absence of Integrase Strand Transfer Inhibitor Associated Resistance in Antiretroviral Therapy Naive and Experienced Individuals from Western India
Absence of Integrase Strand Transfer Inhibitor Associated Resistance in Antiretroviral Therapy Naive and Experienced Individuals from Western India
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DOI：
10.1089/aid.2018.0272
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发表时间：
2019-04-08
影响因子：
1.5
通讯作者：
Sashindran, Vangal Krishnaswamy
中科院分区：
文献类型：
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作者：
Karade, Santosh;Sen, Sourav;Sashindran, Vangal Krishnaswamy
印度国家艾滋病控制计划严重依赖低成本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，需要探索其他抗逆转录病毒药物组合。由于效力更高、疗效更好和耐受性更好，世卫组织最近推荐了以整合酶链转移抑制剂（INSTI）为基础的一线抗逆转录病毒治疗（ART）。印度缺乏INSTI耐药性监测数据。因此，在一线抗逆转录病毒治疗中广泛引入INSTI之前，有必要分析主要感染HIV-1亚型C的印度人群的整合酶（IN）基因。血浆样本采集自向印度浦那ART中心报告的INSTI幼稚个体。提取RNA，用巢式聚合酶链反应（巢式PCR）扩增IN基因。对867 bp的PCR产物进行双向测序，并采用Stanford University HIV耐药算法分析耐药相关突变。来自62例INSTI幼稚个体的58个HIV-1序列成功地进行了基因分型。在这58人中，40人是ART新手，新诊断的，其余的人是NRTI， NNRTI或基于蛋白酶抑制剂的失败方案。研究中发现的最常见亚型是C(93%)，其次是A1（3.5%）。in基因共有191个（66.31%）完全保守氨基酸（aa）位点。总体而言，没有主要的INSTI耐药突变，但E157Q（13.79%）出现了常见的多态性突变。其他辅助突变为L74IM（34.48%）、Q95K（1.72%）和T97A（1.72%）。总之，这是印度首次对主要HIV-1亚型C序列的研究，其特征是in基因的aa变异，并表明没有主要的INSTI耐药相关突变。
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 naive 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 naive individuals were successfully genotyped. Of these 58, 40 were ART naive, 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.