HIV Drug Resistance Monitoring in Chennai, India

印度钦奈的艾滋病毒耐药性监测

基本信息

批准号：
8540028
负责人：
Rami Kantor
金额：
$ 20.69万
依托单位：
MIRIAM HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2015-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8540028
关键词：
Accounting Adherence Alleles Anti-Retroviral Agents Archives Biological Assay Cold Chains Collaborations Consensus Consensus Sequence Cost Effectiveness Analysis Counseling DNA Data Detection Development Drug Monitoring Drug resistance Effectiveness Ensure Epidemic Evaluation Failure Funding Genotype Goals Gold Guidelines HIV HIV Infections HIV drug resistance HIV-1 India Individual Infection Institution Knowledge Laboratories Measures Methods Minority Monitor Mutation Nucleosides Patient Care Patients Pattern Performance Peripheral Blood Mononuclear Cell Pharmaceutical Preparations Plasma Point Mutation Policy Maker Polymerase Chain Reaction Population Predisposition Prevalence Prophylactic treatment Public Health RNA RNA Sequences Regimen Research Research Personnel Resistance Resources Sampling Sensitivity and Specificity Southern Africa Technology Transfer Testing Treatment Failure Treatment outcome United States National Institutes of Health Validation Variant Viral Viral Load result Viral load measurement Virus Whole Blood antiretroviral therapy clinical care cost experience genome sequencing improved innovation laboratory facility new technology non-nucleoside reverse transcriptase inhibitors prevent programs public health relevance rapid detection resistance mutation tool transmission process treatment program treatment site viral RNA

项目摘要

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.

描述（由申请人提供）：HIV-1亚型C引起的感染占印度全球流行病和几乎所有HIV感染的50％以上。耐药性是抗逆转录病毒治疗衰竭的主要原因和结果。基因型抗性测定估计药物敏感性，并为临床医生和政策制定者提供指导。尽管由西方的艾滋病毒治疗指南推荐，但在印度的公共卫生临床护理和其他资源有限的环境中很少进行基因分型，这主要是由于成本和访问限制。该提案将允许在印度钦奈的YRG-Care进行全血检查全血和获得的HIV耐药性；开发印度亚型特异性点突变测定法，该突变是针对抗逆转录病毒疗法失败时最常见的耐药性突变的；并验证点突变测定结果单基因组测序。具体的目的是（1）在印度钦奈的YRGCRE中定义血浆RNA和前病毒DNA中耐药性的患病率。我们将检验前病毒DNA中耐药性突变的检测预测治疗幼稚受试者之间的抗性以及治疗受试者之间的病毒学衰竭的假设。（2）与基因型金标准品相比，研究点突变测定是否具有敏感性和特异性在血浆RNA和前病毒DNA中的关键耐药性突变中是否具有特异性。与种群基因分型相比，我们将探索少数毒素耐药性突变的检测下限，并通过将其与单个基因组测序进行比较的点突变测定，从而验证对耐药性突变的定量。这些具体目标将扩大印度抗HIV耐药性发展的知识，并通过共识测序和创新的点突变测定法比较HIV RNA和DNA耐药性突变。这项印度和美国研究合作将促进技术转移，有可能影响印度的抗HIV耐药性监测和艾滋病毒患者护理。