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在印度泰米尔纳德邦塞勒姆地区,针对初治抗逆转录病毒疗法患者和一线治疗失败患者,利用基因分型和对接分析预测耐药性。

Prediction of drug-resistance using genotypic and docking analysis among anti-retroviral therapy naïve and first-line treatment failures in Salem, Tamil Nadu, India.

作者信息

Dharmalingam Thirunavukkarasu, Udhaya V, Umaarasu T, Elangovan V, Rajesh S V, Shanmugam Gnanendra

机构信息

Department of Microbiology, Raja Muthhaiah Medical College, Annamalai University, Chidambaram, TamilNadu, India.

出版信息

Curr HIV Res. 2015;13(2):160-72. doi: 10.2174/1570162x1302150415111040.

Abstract

The emergence of drug resistance among HIV-positive patients undergoing Anti- Retroviral Therapy (ART) with poor adherence to the HAART is a major concern in India. As the HIV accumulates the key mutations, the drug resistance occurs, that pose challenges to the ART regimens currently being used. Thus, the present study was carried out among the ART- naïve patients attending ART Centre at Salem district, Tamil Nadu, India. The mutations that concern the drug resistance were discriminated by determining the viral load before and after 6 months. The drug resistance was analyzed by HIV genotyping from the patients possessing a viral load of >1000 copies/mL after 6 months of ART. The mutations pertaining to drug resistance were analyzed by the online Stanford HIV Database. The 3D structures of the RT were modeled and the drugs used in the first-line regimens were docked to explore the effect of mutations on the binding pattern of the drugs. Among the 250 patients, the viral load data were obtained for 213 patients. The study found 23 patients with both virological and immunological failures and HIV drug mutations were also revealed by genotyping. The mutations of I135R/T/V/X, L178 I/M, M184V/I, D67N, K70R, and K103N were the most common among these 23 patients. The present study revealed that the NACO recommended first-line ART regimen is efficient in most of the patients attending ART center. The emergence of drug resistance of HIV variant is common even under the best circumstance of ART. This study reveals that there is a necessity for the implementation of improved and economically systematic attempt that allows the clinicians to make a rational choice of therapy regimen to overcome the first-line therapy failures among the ART- naive.

摘要

在印度,接受高效抗逆转录病毒疗法(HAART)但依从性差的HIV阳性患者中出现耐药性是一个主要问题。随着HIV积累关键突变,耐药性就会出现,这对目前使用的抗逆转录病毒疗法方案构成挑战。因此,本研究在印度泰米尔纳德邦塞勒姆区接受抗逆转录病毒治疗初治患者的抗逆转录病毒治疗中心进行。通过测定6个月前后的病毒载量来区分与耐药性相关的突变。对接受抗逆转录病毒治疗6个月后病毒载量>1000拷贝/毫升的患者进行HIV基因分型分析耐药性。通过在线斯坦福HIV数据库分析与耐药性相关的突变。对逆转录酶(RT)的三维结构进行建模,并将一线治疗方案中使用的药物进行对接,以探索突变对药物结合模式的影响。在250名患者中,获得了213名患者的病毒载量数据。研究发现23名患者存在病毒学和免疫学失败情况,基因分型也显示出HIV药物突变。I135R/T/V/X、L178 I/M、M184V/I、D67N、K70R和K103N突变在这23名患者中最为常见。本研究表明,国家艾滋病控制组织(NACO)推荐的一线抗逆转录病毒治疗方案对大多数在抗逆转录病毒治疗中心就诊的患者有效。即使在抗逆转录病毒治疗的最佳情况下,HIV变异体的耐药性出现也很常见。这项研究表明,有必要实施改进的、经济上系统的措施,使临床医生能够合理选择治疗方案,以克服抗逆转录病毒治疗初治患者的一线治疗失败情况。

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