Mentoring Investigators in HIV and Tuberculosis Therapeutics Research

总结 结核病（TB）现在是全球死亡的主要传染性原因，它仍然是全球死亡的头号原因。 艾滋病毒感染者死亡率。一线治疗方案时间长，给患者带来负担 耐药结核病通常需要1-2年的药物治疗， 严重或不可逆转的毒性。结核病药物开发管道现在是强大的，提供了理由， 乐观.然而，为了优化现有的和新的药物，我们必须使用最先进的药物， 开发方法（包括最好地利用定量药理学），新的 开发药物或治疗方案，使其能够用于所有可能从中受益的患者， 包括艾滋病毒携带者、儿童和孕妇。关键的挑战和机遇在于利用 临床药理学作为结核病和艾滋病治疗研究中更有效的工具， 开发和优化频谱。这是此K24中期职业生涯应用程序的上下文 Kelly Dooley，医学博士，博士，医学副教授，药理学，& 约翰霍普金斯大学临床药理学和传染病部的分子科学 大学，为指导学员进行结核病和艾滋病毒方面面向患者的研究提供保护时间 治疗学Dooley博士是少数几位接受过临床培训的传染病专家之一。 在结核病治疗领域工作的药理学。她是全球公认的结核病和艾滋病领域的领导者， 他还参与了相关的结核病治疗研究，并指导（和正在指导）该领域的多名学员。 通过她领导的多项独立资助的研究以及她指导的研究 作为ACTG、TBTC和IMPAACT的结核病科学领导委员会成员 网络，她能够提供良好的机会，培养下一代临床 研究人员在结核病和艾滋病毒的患者为导向的研究。此外，这款K24将使她能够扩大她的 在几个关键领域拥有自己的知识：定量药理学方法，应用于设计和 TB或TB-HIV治疗的临床试验分析;生物标志物鉴定和使用以及 了解药物输送到难以进入的腔室，例如结核性脑膜炎; 和一个新的领域的关键未满足的医疗需求，治疗非结核分枝杆菌（在 感染和不感染艾滋病毒的患者）。这个K24将允许杜利博士有受保护的时间来训练下一个 培养临床药理学和临床研究方面的研究人员，如结核病和艾滋病毒方面的研究人员， 扩大结核病治疗工作中的定量方法;以及 探索新的调查领域。这个奖项所提供的受保护的时间是至关重要的杜利博士 实现这些目标。

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.