HIV Drug Resistance Monitoring in Chennai, India

描述（由申请人提供）：由HIV-1亚型C引起的感染占全球流行病的50%以上，几乎所有的HIV感染都在印度。耐药是抗逆转录病毒治疗失败的主要原因和后果。基因型耐药测定可估计药物敏感性，并为临床医生和决策者提供指导。尽管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环境中，很少在公共卫生临床护理中进行基因分型，主要是由于成本和获取限制。这一建议将允许在印度金奈的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突变的印度亚型c特异性点突变检测；并对点突变试验结果进行验证

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.