Mentoring Investigators in HIV and Tuberculosis Therapeutics Research

指导艾滋病毒和结核病治疗研究的研究人员

• 批准号: 10335264
• 负责人: Kelly E. Dooley
• 金额: $ 17.63万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-21 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10335264
• 关键词: AIDS clinical trial group; Address; Antimycobacterial Agents; Area; Attention; Award; Biological Markers; Brain; Bronchiectasis; Cause of Death; Cerebrospinal Fluid; Child; Clinical; Clinical Drug Development; Clinical Pharmacology; Clinical Research; Clinical Trials; Clinical Trials Network; Cohort Studies; Collaborations; Communicable Diseases; Data; Development; Disease; Doctor of Philosophy; Dose; Drug Delivery Systems; Drug Interactions; Drug resistance in tuberculosis; Ensure; Foundations; Funding; Goals; HIV; HIV/TB; Individual; Interdisciplinary Study; International; International Maternal Pediatric Adolescent AIDS Clinical Trials; Investigation; Irreversible Toxicity; Isoniazid resistance; K-Series Research Career Programs; Knowledge; Lead; Leadership; Learning; Medical; Medicine; Meningeal Tuberculosis; Mentors; Mentorship; Midcareer Investigator Award in Patient-Oriented Research; Molecular; Multidrug-Resistant Tuberculosis; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Pharmacology; Phase; Physicians; Population; Positioning Attribute; Pre-Clinical Model; Pregnant Women; Prevalence; Regimen; Research; Research Design; Research Personnel; Rifampin; Role; Safety; Science; Scientist; Site; Special Population; Specialist; Testing; Therapeutic; Therapeutic Research; Time; Training; Tuberculosis; United States National Institutes of Health; Universities; Work; biomarker discovery; biomarker identification; career; contextual factors; design; drug development; drug distribution; drug-sensitive; experience; improved; innovation; interest; knowledge base; member; mid-career faculty; mycobacterial; next generation; non-tuberculosis mycobacteria; novel therapeutics; optimism; patient oriented research; pharmacologic; pharmacometrics; pre-clinical; programs; skills; tool; treatment optimization; treatment research; treatment response; treatment trial; trial design; tuberculosis drugs; tuberculosis treatment

SUMMARY Tuberculosis (TB) is now the leading infectious cause of death globally, and it remains the #1 cause of death among people living with HIV (PLWH). The first-line regimen is long and burdensome to patients and programs, and drug-resistant TB typically requires treatment for 1-2 years with drugs that can cause severe or irreversible toxicities. The TB drug development pipeline is now robust, providing reason for optimism. To optimize current and new drugs, though, we must employ state-of-the-art drug development approaches (including best use of quantitative pharmacology), and it is imperative that new drugs or regimens be developed so that they can be used in all patients that may benefit from them, including PLWH, children, and pregnant women. Critical challenges and opportunities lie in using clinically pharmacology as a tool more effectively in TB and HIV therapeutics research, across the drug development and optimization spectrum. This is the context for this application for a K24 Mid-Career Development Award for Kelly Dooley, MD, PhD, Associate Professor of Medicine, Pharmacology, & Molecular Sciences in the Divisions of Clinical Pharmacology and Infectious Diseases at Johns Hopkins University, to provide protected time to mentor trainees in patient-oriented research in TB and HIV therapeutics. Dr. Dooley is one of the few Infectious Diseases specialists with training in Clinical Pharmacology working in the TB therapeutics field. She is a globally-recognized leader in TB and HIV- associated TB treatment research and has mentored (and is mentoring) multiple trainees in the field. Through the multiple independently-funded studies she is leading as well as those she is directing in her capacity as a member of the TB scientific leadership committees of the ACTG, TBTC, and IMPAACT networks, she is in a position to provide excellent opportunities to train the next generation of clinical researchers in patient-oriented research in TB and HIV. In addition, this K24 will allow her to expand her own knowledge in several key areas: quantitative pharmacology approaches, as applied to design and analysis in clinical trials of TB or TB-HIV treatment; biomarkers identification and use as well as understanding of drug delivery to hard-to-access compartments, for example in tuberculous meningitis; and a new area of critical unmet medical need, the treatment of nontuberculous mycobacteria (in patients with and without HIV). This K24 will allow Dr. Dooley to have the protected time to train the next generation of investigators in clinical pharmacology and clinical research, as applied to TB and HIV- associated TB, a critical shortage area; expand quantitative approaches in TB therapeutics work; and explore new areas of investigation. The protected time afforded by this award is essential to Dr. Dooley achieving these goals.

概括 结核病（TB）现在是全球领先的感染性死亡原因，它仍然是 艾滋病毒（PLWH）的人死亡。一线方案对患者很长，繁重 和计划，耐药结核病通常需要使用可能导致的药物进行1 - 2年的治疗 严重或不可逆的毒性。结核病药物开发管道现在很强，提供了理由 乐观。但是，要优化当前和新药，我们必须使用最先进的药物 开发方法（包括最佳使用定量药理学），必须新的 开发药物或方案，以便可以在所有可能从中受益的患者中使用它们， 包括PLWH，儿童和孕妇。关键的挑战和机会在于使用 临床药理学作为TB和HIV治疗研究中更有效的工具， 开发和优化谱。这是此应用程序的背景 医学博士凯利·杜利（Kelly Dooley）发展奖，医学，药理学副教授，＆ 约翰·霍普金斯（Johns Hopkins）临床药理学和传染病的分子科学 大学，提供受保护的时间来指导学员在结核病和艾滋病毒中以患者为导向的研究 疗法。 Dooley博士是临床培训的少数传染病专家之一 在结核病治疗领域工作的药理学。她是结核病和艾滋病毒的全球公认领导者 相关的结核病治疗研究，并在该领域指导（并正在指导）多名学员。 通过多项独立资助的研究，她和她指导的研究 作为ACTG，TBTC和Inconcact的结核病科学领导委员会成员的能力 网络，她有能力提供极好的机会来培训下一代临床 结核病和艾滋病毒研究的研究人员。此外，这个K24将使她扩大她 在几个关键领域的知识：用于设计和设计的定量药理学方法 在结核病或结核病治疗的临床试验中分析；生物标志物识别和使用以及 了解药物到难以访问的室内的药物，例如在结核性脑膜炎中； 以及一个新的未满足医疗需求的新领域，治疗无结核分枝杆菌（在 患有和没有艾滋病毒的患者）。这款K24将使Dooley博士能够有受保护的时间来训练下一个 应用于结核病和HIV-的临床药理学和临床研究的研究者生成 相关的结核病，一个关键的短缺区域；扩展结核病治疗学工作中的定量方法；和 探索新的调查领域。该奖项提供的受保护时间对Dooley博士至关重要 实现这些目标。