HIV Drug Resistance Monitoring in Chennai, India

描述(申请人提供)：由艾滋病毒-1 C亚型引起的感染占全球疫情的50%以上，几乎占印度所有艾滋病毒感染的比例。耐药性是抗逆转录病毒治疗失败的主要原因和后果。基因耐药分析评估药物敏感性，并为临床医生和政策制定者提供指导。虽然西方的艾滋病毒治疗指南建议进行基因分型，但在印度和其他资源有限的公共卫生临床医疗机构中，基因分型很少进行，主要是因为成本和获得机会的限制。这项提议将允许在印度金奈的YRG-CARE进行全血传播和获得性艾滋病毒耐药性的检查；开发一种针对抗逆转录病毒治疗失败后最常见的耐药性突变的印度C亚型特异点突变检测方法；以及通过以下方式验证点突变检测结果 单基因组测序。其具体目的是(1)确定在印度金奈YRG-CARE治疗初治和有经验的HIV-1 C亚型感染者中，血浆RNA和前病毒DNA中耐药的流行率。我们将验证这样的假设，即检测前病毒DNA中的耐药突变可以预测治疗初期受试者中的传播耐药性，以及治疗中受试者中的病毒学失败；以及(2)与基因型金标准相比，我们将调查点突变分析在检测血浆RNA和前病毒DNA中的关键耐药突变方面是否敏感和特异。我们将探索少数群体耐药突变的检测下限，并通过点突变试验验证耐药突变的量化，并将其与单基因组测序进行比较。这些具体目标将扩大对印度艾滋病毒耐药性发展的了解，并通过共识测序和创新的点突变试验对艾滋病毒RNA和DNA耐药性突变进行比较。印度和美国的这项研究合作将促进技术转让，这可能会影响印度的艾滋病毒耐药性监测和艾滋病毒患者护理。

DESCRIPTION (provided by applicant): Infection due to HIV-1 Subtype C accounts for more than 50% of the global epidemic and nearly all HIV infections in India. Drug resistance is the major cause and consequence of antiretroviral treatment failure. Genotypic resistance assays estimate drug susceptibility and provide guidance to clinicians and policy makers. Though recommended by HIV treatment guidelines in the West, genotyping is rarely performed in public health clinical care in India and other resource limited settings, mainly due to cost and access constraints. This proposal will allow examination of whole blood for transmitted and acquired HIV drug resistance at YRG-CARE in Chennai, India; development of an Indian subtype-C specific point mutation assay that targets the most common drug resistance mutations that occur upon failure of antiretroviral therapy; and validation of the point mutation assay results by Single Genome Sequencing. The Specific Aims are to (1) define prevalence of drug resistance in plasma RNA and proviral DNA in treatment naive and experienced HIV-1 subtype C infected patients at YRG- CARE in Chennai, India. We will test the hypotheses that the detection of drug resistance mutations in proviral DNA predicts transmitted resistance among treatment naive subjects, and virological failure among subjects on treatment; and (2) investigate whether point mutation assays are sensitive and specific in the detection of key drug resistance mutations in plasma RNA and proviral DNA, compared to genotypic gold standards. We will explore the lower limit of detection of minority drug resistance mutations compared to population genotyping and validate quantification of drug resistance mutations by a point mutation assay comparing it to single genome sequencing. These Specific Aims will expand knowledge of the development of HIV drug resistance in India, and allow comparison of HIV RNA and DNA drug resistance mutations by consensus sequencing and by an innovative point mutation assay. This India and US research collaboration will promote technology transfer that has the potential to impact HIV drug resistance surveillance and HIV patient care in India.