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Antiretroviral pharmacogenomics, pharmacokinetics and toxicity in neuroAIDS

神经艾滋病中的抗逆转录病毒药物基因组学、药代动力学和毒性

基本信息

批准号：
8860246
负责人：
Qing Ma
金额：
$ 11.98万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8860246
关键词：
Animal Model Anti-Retroviral Agents Applications Grants Area Atazanavir Award Bioinformatics Biological Models Brain Buffaloes Candidate Disease Gene China Chinese People Clinical Clinical Investigator Clinical Trials Comorbidity Control Groups DNA Data Development Disease Progression Disease model Dose Drug Kinetics Environment Enzymes Etiology Evaluation Exhibits Foundations Gene Expression Gene Expression Profiling Genes Genetic Genetic Markers Genetic Polymorphism Genetic Variation Genomics Genotype Goals HIV HIV-associated neurocognitive disorder Immunology Individual Inflammation Intervention Lead Link Lopinavir Measures Membrane Transport Proteins Mentors Mentorship Modeling Molecular Profiling Morbidity - disease rate Neuraxis Neurocognitive Nevirapine P-Glycoprotein Pathogenesis Patient Care Patients Penetration Peripheral Pharmaceutical Preparations Pharmacogenomics Plasma Population Prognostic Marker Proteins RNA Regimen Research Research Activity Research Personnel Research Training Resistance Risk Risk Assessment Role Sampling Severities Techniques Testing Toxic effect Training Training Activity Universities Variant Work antiretroviral therapy base brain metabolism career career development case control disorder control drug distribution drug metabolism efavirenz genetic analysis genetic variant improved interest neuroAIDS neurocognitive disorder neurotoxicity novel diagnostics personalized medicine prevent research study response simulation skills therapeutic target tool virology

项目摘要

DESCRIPTION (provided by applicant): The overall objective of this proposal is to provide advanced training for the career development of Dr. Qing Ma, a clinical pharmacologist, in antiretroviral pharmacogenomics, pharmacokinetics and disease modeling in patients with HIV-associated neurocognitive disorders. Through research training, coursework and independent studies, he will develop collaborative relationship with his mentors and skills to achieve his long- term career goal to become an independent clinical investigator focusing on pharmacogenomics of antiretroviral therapy and neurocognitive disorders. He will be working in a rich environment under successful senior investigators from University at Buffalo (Dr. Gene Morse), Vanderbilt University (Dr. David Haas) and University of Rochester (Dr. Giovanni Schifitto). Specific areas of mentorship and training include pharmacogenomics, genetic analysis and bioinformatics, population pharmacokinetic analysis and disease modeling. This proposal focuses on the genomic impact on antiretroviral pharmacokinetics, response and toxicity in patients with HIV-associated neurocognitive disorders (HAND), one of the most prevalent co- morbidities in treated individuals. To achieve this immediate goal, patient samples and longitudinal data will be used from two well-characterized studies: CNS HIV Antiretroviral Therapy Effects Research (CHARTER) and Clinical Trial of CNS Penetrating ART to Prevent NeuroAIDS in China. The risk for HAND may be related to limited distribution of antiretrovirals into the brain but the specific genetic factors associated with variations in brain exposure are largely unknown. Our central hypothesis is that genetic variants that are associated with antiretroviral pharmacokinetics and neurotoxicity will also be associated with HAND in treated individuals. The specific aims of the proposed research are: 1) to determine the association between antiretroviral pharmacokinetics and neurocognitive function among treated patients from CHARTER and Chinese studies; 2) to identify genes and genetic polymorphisms that are associated with antiretroviral exposure, particularly genes that are linked to drug metabolism and drug distribution into the central nervous system; 3) to identify neurotoxicity and inflammation-associated genes that are linked to neurocognitive abnormalities using gene expression profiling and bioinformatics techniques; 4) to develop a disease progression model that integrates pharmacokinetics and the genetic data generated from aims 1 to 3 to predict HAND development. The identification of genetic markers correlated with antiretroviral pharmacokinetics and neurocognitive function will shed lights on HAND etiology and will provide patients and clinicians a useful tool for intervention and risk assessment on an individualized basis. The proposed training and research activities will provide Dr. Qing Ma a foundation that he can generate competitive grant applications in the final years of the award and advance patient care through personalized medicine.

描述（由申请人提供）：