HIV Drug Resistance Monitoring in Chennai, India

描述（由申请人提供）：HIV-1亚型C感染占全球流行病的50%以上，几乎占印度所有HIV感染。耐药性是抗逆转录病毒治疗失败的主要原因和后果。基因型耐药检测可评估药物敏感性，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，但在印度和其他资源有限的环境中，基因分型很少在公共卫生临床护理中进行，主要是由于成本和获取限制。该提案将允许在印度Chennai的YRG-CARE对全血进行传播和获得性艾滋病毒耐药性检查;开发针对抗逆转录病毒治疗失败后发生的最常见耐药性突变的印度C亚型特异性点突变检测;并通过以下方法验证点突变检测结果： 单基因组测序。具体目的是（1）在YRG- CARE（Chennai，India）确定未经治疗和有治疗经验的HIV-1 C亚型感染患者的血浆RNA和前病毒DNA耐药率。我们将检验以下假设：检测前病毒DNA中的耐药突变可预测未接受过治疗的受试者中的传播性耐药，以及接受治疗的受试者中的病毒学失败;（2）研究与基因型金标准相比，点突变检测法在检测血浆RNA和前病毒DNA中的关键耐药突变方面是否具有灵敏度和特异性。我们将探索与群体基因分型相比少数耐药突变的检测下限，并通过点突变试验与单基因组测序进行比较，验证耐药突变的定量。这些具体目标将扩大印度艾滋病毒耐药性发展的知识，并允许通过共识测序和创新的点突变检测来比较艾滋病毒RNA和DNA耐药性突变。印度和美国的研究合作将促进技术转让，这有可能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.