Impact of HIV infection on early responses to TB exposure

HIV 感染对结核病暴露早期反应的影响

基本信息

批准号：
10379927
负责人：
Sara Auld
金额：
$ 14.96万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-04-01 至 2024-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10379927
关键词：
Acceleration Address Adult Affect Alveolar Macrophages Anti-Inflammatory Agents Apoptosis Area Award Biological Assay Biometry Bronchoscopy CD4 Lymphocyte Count Cause of Death Cells Characteristics Clinical Clinical Investigator Clinical Research Communicable Diseases Communities Data Defect Development Plans Disease Eligibility Determination Epidemic Epidemiology Exposure to Functional disorder Funding Future Goals HIV HIV Infections HIV Seronegativity HIV Seropositivity HIV/TB Household Human Immune System Diseases Immunologic Deficiency Syndromes Immunologics Immunologist Immunology Impairment Incidence Individual Inflammatory Inflammatory Response Infrastructure Interferon Type II Interleukin-10 Interleukin-2 International Intervention K-Series Research Career Programs Kenya Knowledge Lung Lung immune response Macrophage Mediating Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Methodology NIH Office of AIDS Research Natural Immunity Outcome Participant Patients Persons Phenotype Positioning Attribute Prospective Studies Prospective cohort Public Health Pulmonary Tuberculosis Pulmonology Regression Analysis Research Research Project Grants Resources Risk Scientist Site T cell response T-Lymphocyte T-Lymphocyte Subsets TNF gene Techniques Testing Time Training Translating Tuberculin Test Tuberculosis United States National Institutes of Health Universities Work adaptive immunity antiretroviral therapy career development clinical epidemiology co-infection cohort collaborative environment comorbidity cytokine design experience improved indexing infection risk insight lung injury mortality multidisciplinary pathogen prevent programs progression risk prospective public health research recruit research and development response screening secondary analysis statistics translational immunology translational study

项目摘要

Project Summary/Abstract This K23 proposal outlines a 5-year career development plan and research strategy that will enable Sara Auld, MD, MSc, to build on her background in global TB/HIV research and clinical epidemiology and gain critical training in prospective clinical research, advanced biostatistics, and T cell and pulmonary immunology. To achieve independence as a clinical investigator with a unique niche as a practicing pulmonologist and an expertise in the epidemiologic and immunologic consequences of TB-HIV coinfection, Dr. Auld requires further training in: 1) recruitment and management of prospective cohorts, specifically the conduct of clinical studies in resource-limited international settings; 2) advanced statistics, including multilevel regression analyses capable of adjusting for household and individual-level characteristics; and 3) translational immunology, with a focus on T cell and pulmonary immune responses to TB exposure. Dr. Auld has outlined a plan of didactic coursework and assembled a multidisciplinary mentorship team. Her primary mentor is Dr. Neel Gandhi, an expert in clinical epidemiology and the conduct of global TB/HIV research. Her co-mentors are Dr. Cheryl Day, a translational immunologist with an expertise in human T cell immunology in TB/HIV coinfection, Dr. Lance Waller, a biomedical statistician with decades of experience in public health research, and Dr. David Guidot, a renowned pulmonary clinician scientist with a robust research program exploring HIV-mediated lung injury and alveolar macrophage dysfunction. With the support of this K23 award, Dr. Auld will address the question of how HIV infection impacts the response to TB exposure. She will first leverage data generated by the screening protocols of the Emory/NYU TB Research Unit (TBRU; U19 AI111211) to determine how HIV affects the acquisition of TB infection among household contacts of TB patients in Kisumu, Kenya (Aim 1). Next, levels of pro-inflammatory, anti- inflammatory, and regulatory cytokines generated by TB-specific T cells, and the phenotype of those cells will be compared for household contacts with and without HIV (Aim 2). Finally, pulmonary immune responses to TB will be compared for people with and without HIV using research bronchoscopy in a separate cohort in Atlanta, GA (Aim 3). Knowledge gained from this study will translate into interventions to decrease the risk of TB infection and improve long-term outcomes for people with HIV. This research responds directly to the 2016 priority areas of the NIH Office of AIDS Research, which considers HIV-associated comorbidities such as TB to be a high priority topic. Emory University provides an exceptional intellectual and collaborative environment for this research. By building upon her prior research experience and training, the well-established TBRU research program in western Kenya, and methodologic training via coursework and expert mentorship, Dr. Auld is well positioned to accomplish the proposed aims and, ultimately, to apply for an R01 award focused on exploring the pulmonary response to TB exposure in a setting with a high burden of TB/HIV coinfection.

项目概要/摘要该 K23 提案概述了 5 年职业发展计划和研究策略，将使 Sara Auld，医学博士、理学硕士，以她在全球结核病/艾滋病毒研究和临床流行病学方面的背景为基础，并获得了前瞻性临床研究、高级生物统计学、T 细胞和肺部免疫学方面的关键培训。实现作为一名临床研究者的独立性，作为一名执业肺科医生和一名具有独特地位的临床研究者 Auld 博士需要进一步了解 TB-HIV 合并感染的流行病学和免疫学后果方面的专业知识培训：1）前瞻性队列的招募和管理，特别是临床研究的进行资源有限的国际环境； 2) 高级统计，包括多级回归分析能力针对家庭和个人层面的特征进行调整； 3）转化免疫学，重点是 T 细胞和肺部对结核病暴露的免疫反应。奥尔德博士概述了教学课程计划并组建了一支多学科的指导团队。她的主要导师是尼尔·甘地博士，一位临床流行病学和全球结核病/艾滋病毒研究的开展。她的共同导师是 Cheryl Day 博士，转化免疫学家，在结核病/艾滋病毒合并感染的人类 T 细胞免疫学方面拥有专业知识，兰斯博士 Waller 是一位拥有数十年公共卫生研究经验的生物医学统计学家，David Guidot 博士是一位著名的肺部临床科学家，拥有强大的研究项目，探索艾滋病毒介导的肺损伤和肺泡巨噬细胞功能障碍。在 K23 奖项的支持下，Auld 博士将解决 HIV 感染如何影响人类健康的问题。对结核病暴露的反应。她将首先利用埃默里大学/纽约大学筛选协议生成的数据结核病研究单位（TBRU；U19 AI111211）确定艾滋病毒如何影响结核病感染肯尼亚基苏木结核病患者的家庭接触者（目标 1）。其次，促炎、抗炎水平结核病特异性 T 细胞产生的炎症和调节性细胞因子，这些细胞的表型将比较感染和未感染艾滋病毒的家庭接触者（目标 2）。最后，肺部免疫反应将使用研究性支气管镜检查在一个单独的队列中对感染和未感染艾滋病毒的人进行结核病比较佐治亚州亚特兰大（目标 3）。从这项研究中获得的知识将转化为干预措施，以降低风险结核病感染并改善艾滋病毒感染者的长期结果。这项研究直接回应了 2016 年美国国立卫生研究院艾滋病研究办公室的优先领域，该办公室将结核病等与艾滋病毒相关的合并症视为成为一个高度优先的主题。埃默里大学为学生提供了卓越的智力和协作环境这项研究。基于她之前的研究经验和培训，完善的 TBRU 研究 Auld 博士在肯尼亚西部的项目以及通过课程作业和专家指导进行的方法培训方面表现出色定位于实现拟议目标，并最终申请专注于探索的 R01 奖项在结核病/艾滋病毒双重感染负担较高的环境中，肺部对结核病暴露的反应。

项目成果

期刊论文数量（23）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Closing the book on Category II: time for individualized regimens for patients with recurrent tuberculosis.

结束第二类书籍：为复发性结核病患者制定个体化治疗方案的时间到了。

DOI：
发表时间：
2018
期刊：
影响因子：
0
作者：
Auld, Sara C;Gandhi, Neel R;Shah, N Sarita
通讯作者：
Shah, N Sarita

Convergence of non-communicable diseases and tuberculosis: a two-way street?

非传染性疾病与结核病的融合：一条双向路？

DOI：
发表时间：
2018-11-01
期刊：
影响因子：
0
作者：
Magee, M J;Salindri, A D;Gujral, U P;Auld, S C;Bao, J;Haw, J S;Lin, H;Kornfeld, H
通讯作者：
Kornfeld, H

HIV and the tuberculosis "set point": how HIV impairs alveolar macrophage responses to tuberculosis and sets the stage for progressive disease.

HIV 和结核病“设定点”：HIV 如何损害肺泡巨噬细胞对结核病的反应并为疾病进展奠定基础。

DOI：
发表时间：
2020-09-23
期刊：
影响因子：
3.3
作者：
Auld, Sara C;Staitieh, Bashar S
通讯作者：
Staitieh, Bashar S

Fibrinolysis Shutdown and Thrombosis in a COVID-19 ICU.

COVID-19 ICU 中的纤溶关闭和血栓形成。

DOI：
发表时间：
2021-03-01
期刊：
影响因子：
0
作者：
Creel;Auld, Sara C;Caridi;Barker, Nicholas A;Friend, Sarah;Gaddh, Manila;Kempton, Christine L;Maier, Cheryl L;Nahab, Fadi;Sniecinski, Roman
通讯作者：
Sniecinski, Roman

Lung Function After Coronavirus Disease 2019: Some Answers, More Questions.

2019 年冠状病毒病后的肺功能：一些答案，更多问题。