Evaluation of novel tuberculosis screening strategies for people living with HIV

描述（由申请人提供）：这是克里斯蒂娜·尹博士的K23奖申请，她是加州大学旧金山分校的肺病学家。尹博士正在成为一名以患者为导向的HIV/TB临床研究的年轻研究者。K23奖将为尹博士提供必要的支持，以实现以下目标：1)成为hiv相关结核病（TB）患者导向临床研究的专家；2)在国际范围内开展结核病筛查和诊断试验的临床调查3)在临床研究中采用先进的生物统计学方法；4)对卫生保健干预措施进行经济评价。为了实现这些目标，Yoon博士组建了一个指导团队，其中包括主要导师Laurence Huang博士（艾滋病毒相关呼吸道感染研究的国际专家）和两位共同导师：结核病诊断和实施科学研究专家Adithya Cattamanchi博士；Saunak Sen博士是一位生物统计学家，擅长统计遗传学。如果不实施异烟肼预防疗法等结核病预防疗法，就无法在艾滋病毒感染者中实现结核病的有效控制。世卫组织目前推荐用于确定IPT资格的基于症状的结核病筛查未能确定三分之二以上有资格接受这种挽救生命和具有成本效益的干预措施的艾滋病毒感染者。尹医生申请的目的是评估

DESCRIPTION (provided by applicant): This is an application for a K23 award for Dr. Christina Yoon, a pulmonologist at the University of California, San Francisco. Dr. Yoon is establishing herself as a young investigator in patient-oriented clinical research of HIV/TB. This K23 award will provide Dr. Yoon with the support necessary to accomplish the following goals: 1) to become expert at patient-oriented clinical research in HIV-associated tuberculosis (TB); 2) to conduct clinical investigations of TB screening and diagnostic tests in an international setting 3) to implement advanced biostatistical methods in clinical studies; 4) to conduct economic evaluations of healthcare interventions. To achieve these goals, Dr. Yoon has assembled a mentoring team comprised of a primary mentor Dr. Laurence Huang, an international expert in HIV-associated respiratory infection research, and two co-mentors: Dr. Adithya Cattamanchi, an expert in TB diagnostics and implementation science research; Dr. Saunak Sen, a biostatistician with expertise in statistical genetics. Effective control of TB among people living with HIV (PLHIV) cannot be achieved without implementation of TB preventive therapies such as isoniazid preventive therapy (IPT). The current symptom-based TB screen recommended by the WHO to determine IPT eligibility fails to identify more than two-thirds of PLHIV eligible for this life-saving and cost-effective intervention. The objective of Dr. Yoon's application is to evaluate novel biomarkers that have strong potential to improve scale-up of IPT. The first two Aims focus on an immediately deployable, inexpensive (<2 USD), rapid (3 minutes), and simple-to-use point-of-care (POC) assay for C- reactive protein (CRP). In Aim 1, Dr. Yoon will use the existing research infrastructure of Dr. Huang's NIH- funded International HIV-associated Opportunistic Pneumonia Study to expand her current pilot study to enroll 500 additional HIV-infected Ugandans initiating antiretroviral therapy to compare the diagnostic accuracy and predictive values of POC CRP vs. the WHO symptom screen for active TB. In Aim 2, Dr. Yoon will use decision analysis with Markov modeling to project the incremental cost-effectiveness of POC CRP-based TB screening. In Aim 3, Dr. Yoon proposes to further advance the field by evaluating whether a host blood transcriptional signature can further improve selection of patients for IPT. Using clinical data and banked specimens from Aim 1, Dr. Yoon will conduct a nested case-control study to evaluate the high sensitivity, specificity, and predictive values of this signature in the context of TB screening, laying the necessary groundwork for the potential development of this marker into a future POC assay. These studies are significant because they represent the first step in a continuum of research that may lead to improved approaches to TB screening, increased uptake of IPT, and decreased TB incidence among PLHIV worldwide. This research will form the basis for future work investigating the impact of TB screening strategies on IPT initiation and clinically important outcomes, which will be proposed in an R01 grant application before the end of the K23 award period.