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：
8709987
负责人：
Rami Kantor
金额：
$ 21.04万
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 2016-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8709987
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 C 亚型感染占全球流行病的 50% 以上，在印度几乎占所有 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。基因型耐药性测定可评估药物敏感性，并为临床医生和政策制定者提供指导。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地区的公共卫生临床护理中很少进行基因分型，这主要是由于成本和获取的限制。该提案将允许在印度钦奈的 YRG-CARE 对全血进行传播性和获得性 HIV 耐药性检查；开发印度 C 亚型特异性点突变检测，针对抗逆转录病毒治疗失败时发生的最常见耐药突变；并验证点突变测定结果单基因组测序。具体目标是 (1) 确定印度钦奈 YRG-CARE 初次治疗和经历过 HIV-1 C 亚型感染患者血浆 RNA 和前病毒 DNA 耐药性的流行情况。我们将测试以下假设：检测前病毒 DNA 中的耐药突变可预测未接受治疗的受试者中的传播耐药性以及接受治疗的受试者中的病毒学失败； (2) 与基因型金标准相比，研究点突变检测在检测血浆 RNA 和前病毒 DNA 中关键耐药突变方面是否灵敏且特异。我们将探索与群体基因分型相比的少数耐药突变的检测下限，并通过将其与单基因组测序进行比较的点突变测定来验证耐药突变的量化。这些具体目标将扩大对印度 HIV 耐药性发展的了解，并允许通过共识测序和创新的点突变测定来比较 HIV RNA 和 DNA 耐药性突变。印度和美国的这项研究合作将促进技术转让，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。