HIV-1 Therapeutics and Drug Resistance

HIV-1 治疗和耐药性

基本信息

批准号：
7248825
负责人：
Daniel R. Kuritzkes
金额：
$ 11.66万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-06-01 至 2011-05-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7248825
关键词：
AIDS clinical trial group Acquired Immunodeficiency Syndrome Acute Address Adipocytes Adipose tissue Adult Affinity Age Alleles Anti-Retroviral Agents Antiviral Therapy Area Atazanavir Autologous Award Biological Assay Biometry Body Composition Body fat Botswana Breast Feeding CCR5 gene CD4 Lymphocyte Count CD4 Positive T Lymphocytes Carbohydrates Clinical Clinical Investigator Clinical Research Clinical Trials Clinical Trials Cooperative Group Clinical Trials Design Codon Nucleotides Colorado Communicable Diseases Complex Cross-Sectional Studies DEXA DNA DNA Vaccines Data Detection Development Disease Disease Progression Dose Drug resistance Educational workshop Endopeptidases Energy Metabolism Enrollment Escape Mutant Exposure to Faculty Fatty acid glycerol esters Filgrastim Funding Future Gagging Generations Genotype Goals Government Grant Growth Guidelines HIV HIV-1 HIV-Associated Lipodystrophy Syndrome Health Sciences Hematopoietic Stem Cell Mobilization High Density Lipoprotein Cholesterol Highly Active Antiretroviral Therapy Hormones Hospitals Human Human Cloning Hyperlipidemia Immune Immune response Immunity In Vitro Individual Infant Infection Inhibitory Concentration 50 Insulin International Interruption Joints Label Laboratories Laboratory Research Lamivudine Lamivudine/Zidovudine Lead Length Leptin Limb structure Link Lipids Lipodystrophy Lopinavir/Ritonavir Macaca mulatta Manuscripts Measurement Measures Mediation Medicine Mentors Mentorship Metabolic Metabolism Mid-Career Clinical Scientist Award (K24)Minor Minority Modeling Molecular Molecular Biology Mothers Multi-Drug Resistance Mutation NNRTI-resistance Nevirapine Numbers Obesity Octanes Pathogenicity Patients Peptide Hydrolases Perinatal Peripheral Persons Pharmaceutical Preparations Phase Phase II Clinical Trials Phenotype Phylogenetic Analysis Pilot Projects Plasma Population Poxviridae Predisposition Prevention Primates Principal Investigator Progress Reports Prophylactic treatment Protease Inhibitor Protocols documentation Provider Public Health Publications Publishing RNA RNA-Directed DNA Polymerase Randomized Randomized Clinical Trials Randomized Controlled Trials Range Rate Recombinants Relative (related person)Reporting Research Research Ethics Research Personnel Resistance Resources Rest Restart Reverse Transcriptase Inhibitors Ritonavir Safety Salvage Therapy Sampling San Francisco Sch417690 Secure Serum Site Stavudine Subgroup T-20 Technology Tenofovir Testing Thailand Therapeutic Therapeutic Effect Thymidine Time Training Treatment Protocols Trees Triiodothyronine Tropism Universities Vaccination Vaccine Design Vaccines Variant Vertical Disease Transmission Viral Viral Drug Resistance Virus Virus Replication Visceral Visit Week Withdrawal Woman Work Zalcitabine Zidovudine abacavir adiponectin analog antiretroviral therapy base career cohort cost design efavirenz emtricitabine env Genes experience falls feeding fitness immunogenicity improved in vivo inhibitor/antagonist instructor insulin sensitivity interest intravenous glucose tolerance test medical schools men mutant non-nucleoside reverse transcriptase inhibitors novel therapeutics octane oxidation patient oriented patient oriented research pol genes pressure professor programs prophylactic receptor recombinant virus research study response therapeutic vaccine tool trial comparing virology wasting

项目摘要

DESCRIPTION (provided by applicant): This application proposes continuation of a broadly-based program for mentoring junior investigators in AIDS-related patient-oriented research. This proposal builds on existing resources of the Division of Infectious Diseases at Brigham & Women's Hospital, including an NIH-funded Adult AIDS Clinical Trials Unit, an Adult ACTG Virology Support Laboratory, the Harvard Medical School Center for AIDS Research, NIH-funded institutional AIDS training grants, and R01-funded research of the applicant. Clinical and research fellows as well as junior faculty interested in pursuing careers in retroviral therapeutics and translational virology will be mentored by the applicant. Course work in molecular biology, biostatistics, HIV-1 medicine, clinical trials design, responsible conduct of research and the ethics of human research will be offered. The research component of this proposal focuses on clinical investigation and formal clinical trials of HIV-1 therapeutics, drug resistance, and viral fitness. Ongoing patient-oriented research under the applicants direction comprises an array of studies with the overall goal of developing novel therapeutic approaches for the treatment of HIV-1 infection, and understanding the interplay between drug resistance, immune escape, and viral fitness. Specific research aims of this proposal are 1) to characterize CCR5 affinity, co-receptor tropism, and fitness of HIV-1 variants resistant to the CCR5 inhibitor SCH-417690 that emerge in subjects participating in a phase 2 trial of this drug (ACTG protocol A5211); 2) to characterize the fitness of immune escape mutants arising during the analytic treatment interruption phase of therapeutic vaccine trial (ACTG protocol A5197); and 3) to determine the influence of the HLA A*0201 allele on the rate of reversion of protease inhibitor resistance mutations in subjects interrupting a failing protease inhibitor. This research program provides a framework within which the applicant can mentor beginning clinical investigators in patient-oriented research focused on critical issues in HIV-1 medicine.

描述（由申请人提供）：本申请建议继续开展一项基础广泛的计划，以指导初级研究人员进行与艾滋病相关的以患者为导向的研究。该提案以布莱根妇女医院传染病科的现有资源为基础，包括 NIH 资助的成人艾滋病临床试验单位、成人 ACTG 病毒学支持实验室、哈佛医学院艾滋病研究中心、NIH 资助的艾滋病机构培训补助金，以及申请人的 R01 资助的研究。申请人将指导有兴趣从事逆转录病毒治疗和转化病毒学职业的临床和研究人员以及初级教师。将提供分子生物学、生物统计学、HIV-1医学、临床试验设计、负责任的研究行为和人类研究伦理方面的课程。该提案的研究部分侧重于 HIV-1 疗法、耐药性和病毒适应性的临床调查和正式临床试验。在申请人的指导下正在进行的以患者为导向的研究包括一系列研究，总体目标是开发治疗HIV-1感染的新治疗方法，并了解耐药性、免疫逃逸和病毒适应性之间的相互作用。该提案的具体研究目标是 1) 表征参与该药物 2 期试验的受试者中出现的对 CCR5 抑制剂 SCH-417690 具有抗性的 HIV-1 变异体的 CCR5 亲和力、共受体向性和适应性（ACTG 方案） A5211）； 2) 表征治疗性疫苗试验的分析治疗中断阶段出现的免疫逃逸突变体的适应性（ACTG方案A5197）； 3) 确定 HLA A*0201 等位基因对中断失败的蛋白酶抑制剂的受试者中蛋白酶抑制剂抗性突变的逆转率的影响。该研究计划提供了一个框架，申请人可以在该框架内指导刚起步的临床研究人员进行以患者为导向的研究，重点关注 HIV-1 医学的关键问题。