Evaluation of novel tuberculosis screening strategies for people living with HIV

艾滋病毒感染者新型结核病筛查策略的评估

• 批准号: 8789754
• 负责人: Christina Yoon
• 金额: $ 18.28万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-05 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8789754
• 关键词: Acquired Immunodeficiency Syndrome; Acute-Phase Proteins; Address; Adult; Affect; Africa South of the Sahara; Applications Grants; Biological Assay; Biological Markers; Biostatistical Methods; Blood; C-reactive protein; California; Characteristics; Clinic; Clinical Data; Clinical Research; Clinical Trials; Communities; Data; Databases; Decision Analysis; Development; Diagnostic; Diagnostic tests; Eligibility Determination; Enrollment; Epidemic; Evaluation; Funding; Future; Genetic; Goals; HIV; Healthcare; Incidence; Infection; Interleukin-6; International; Intervention; Joints; Lead; Life; Low income; Measures; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Morbidity - disease rate; Nested Case-Control Study; Outcome; Outcome Study; Patient Selection; Patients; Pilot Projects; Pneumonia; Predictive Value; Prevention strategy; Preventive; Prospective Studies; Relative (related person); Research; Research Infrastructure; Research Personnel; Resources; Respiratory Tract Infections; Rural; San Francisco; Sensitivity and Specificity; Serum; Site; Specificity; Specimen; Symptoms; Testing; Transcript; Treatment outcome; Tuberculosis; Uganda; United States National Institutes of Health; Universities; Validation; Work; World Health Organization; antiretroviral therapy; base; cost effective; cost effectiveness; diagnostic accuracy; economic evaluation; effective intervention; follow-up; implementation science; improved; isoniazid; markov model; mortality; novel; novel marker; patient oriented; point of care; prevent; programs; public health relevance; scale up; screening; skills; tool; uptake

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.

描述（由申请人提供）：这是一份K23奖的申请，申请人是加州大学弗朗西斯科分校的肺病学家Christina Yoon博士。Yoon博士正在将自己打造成一名年轻的研究人员，从事以患者为导向的艾滋病毒/结核病临床研究。该K23奖项将为Yoon博士提供必要的支持，以实现以下目标：1）成为艾滋病毒相关结核病（TB）以患者为导向的临床研究专家; 2）在国际环境中进行结核病筛查和诊断测试的临床研究3）在临床研究中实施先进的生物统计方法; 4）对医疗干预措施进行经济评估。为了实现这些目标，Yoon博士组建了一个指导团队，由主要导师Laurence Huang博士（HIV相关呼吸道感染研究的国际专家）和两位共同导师组成：Adithya Cattamanchi博士（结核病诊断和实施科学研究专家）; Saunak Sen博士（具有统计遗传学专业知识的生物统计学家）。如果不实施结核病预防性治疗，如异烟肼预防性治疗（IPT），就无法在艾滋病毒感染者（PLHIV）中有效控制结核病。目前世卫组织推荐的用于确定IPT资格的基于ESTA的结核病筛查未能确定超过三分之二的艾滋病毒感染者有资格获得这种挽救生命和具有成本效益的干预措施。尹博士申请的目的是评估 新的生物标志物，具有很强的潜力，以改善规模扩大的IPT。前两个目标专注于C-反应蛋白（CRP）的可立即部署、廉价（<2 USD）、快速（3分钟）和易于使用的即时（POC）检测。在目标1中，Yoon博士将利用Huang博士的NIH资助的国际HIV相关肺炎研究的现有研究基础设施，扩大她目前的试点研究，再招募500名开始抗逆转录病毒治疗的艾滋病毒感染乌干达人，以比较POC CRP与WHO症状筛查对活动性结核病的诊断准确性和预测价值。在目标2中，Yoon博士将使用马尔可夫模型的决策分析来预测基于POC CRP的结核病筛查的增量成本效益。在目标3中，Yoon博士提出通过评估宿主血液转录特征是否可以进一步改善IPT患者的选择来进一步推进该领域。Yoon博士将使用Aim 1的临床数据和库存标本进行巢式病例对照研究，以评估该标记在结核病筛查背景下的高灵敏度，特异性和预测值，为该标记物未来发展为POC检测奠定必要的基础。这些研究意义重大，因为它们代表了一系列研究的第一步，这些研究可能导致改进结核病筛查方法，增加IPT的使用，并降低全球艾滋病毒感染者中的结核病发病率。这项研究将成为未来工作的基础，调查结核病筛查策略对IPT启动和临床重要结果的影响，这将在K23奖励期结束前在R 01赠款申请中提出。