HIV activation in secondary pulmonary infection

继发性肺部感染中的 HIV 激活

• 批准号: 8666385
• 负责人: Michael D. Weiden
• 金额: $ 14.75万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2015-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8666385
• 关键词: Acquired Immunodeficiency Syndrome; Algorithms; Anti-Retroviral Agents; Bacterial Pneumonia; Biological Assay; Biological Models; Biometry; Blood; Bronchoalveolar Lavage; Caring; Cells; Characteristics; Chest; Clinical; Clinical Investigator; Clinical Services; Collaborations; Data Set; Diagnosis; Disease; Enrollment; Epidemiology; Evolution; Flow Cytometry; Frequencies; Funding; Goals; Grant; HIV; HIV Seropositivity; HIV-1; Individual; Infection; Laboratories; Lead; Learning; Leukocytes; Liquid substance; Longitudinal Studies; Lung; Medical; Mentors; Mid-Career Clinical Scientist Award (K24); Midcareer Investigator Award in Patient-Oriented Research; Molecular; Mutation; New York; Pathogenesis; Patient Care; Patients; Pharmaceutical Preparations; Physicians; Plasma; Process; Production; Prospective Studies; Pulmonary function tests; Questionnaires; Regulatory T-Lymphocyte; Research; Research Subjects; Sampling; Site; Specimen; Surface; Surrogate Markers; Techniques; Testing; Training; Translational Research; V3 Loop; Viral; Viral Load result; Virus; Work; antiretroviral therapy; case control; cohort; cytokine; experience; improved; interest; longitudinal course; next generation; novel; novel strategies; peripheral blood; programs; respiratory

DESCRIPTION (provided by applicant): I am a clinical investigator with a research interest in the pathobiology of pulmonary infections. I perform molecular assays on clinical samples obtained by bronchoalveolar lavage and then conduct mechanistic studies in model systems. This approach has been productive and has been effective in training clinical investigators. A recently funded R01-supported study, for which I am a co-PI, is titled "Longitudinal Studies of HIV-Associated Bacterial Pneumonia." This study extends the work of the laboratory to investigate bacterial pneumonia. The hypothesis of this study is that HIV-positive individuals receiving antiretroviral therapy will continue to develop bacterial pneumonia and other pulmonary infections that will lead to characteristic cellular recruitment and activation in the lung. This process will enhance HIV-1 replication and mutation, accelerating the course of AIDS. The longitudinal study is the subject of the research section of this grant. This project represents an extension of my research approach. The hypothesis will be tested via nested case control analysis of a prospectively assembled cohort with surrogate markers of disease as endpoints. I currently spend 45% effort in clinical service. The K24 Midcareer Investigator Award in Patient-Oriented Research would enable me to reduce patient care responsibilities to 10% effort, so I can increase my focus on training the next generation of clinical investigators. I will be able to increase by 2-fold the number of physicians who I can adequately mentor in translational research. A second goal of the K24 award is to obtain focused training in epidemiology and biostatistics. This didactic experience will enhance my collaboration with biostatisticians and will allow me to learn the quantitative techniques required to analyze large data sets. The K24 will also support a collaboration with Dr. llana Belitskaya-Levy, a biostatistician with expertise in hierarchical clustering and HIV mutational analysis. We will develop novel algorithms to stratify patients and analyze viral evolution over the course of the longitudinal grant. The support provide by the K24 award will enhance my potential to participate in translational research programs that develop effective, novel strategies for the improved care of HIV-infected patients with secondary pulmonary infections.

描述（由申请人提供）：我是一名临床研究者，研究兴趣是肺部感染的病理生物学。我对通过支气管肺泡灌洗获得的临床样本进行分子检测，然后在模型系统中进行机制研究。这种方法是富有成效的，在培训临床研究者方面是有效的。最近一项由R 01资助的研究，我是其中的一名共同PI，名为“HIV相关细菌性肺炎的纵向研究”。“这项研究扩展了实验室研究细菌性肺炎的工作。这项研究的假设是，接受抗逆转录病毒治疗的艾滋病毒阳性个体将继续发展细菌性肺炎和其他肺部感染，这将导致肺部特征性细胞募集和激活。这一过程将增强HIV-1的复制和突变，加速艾滋病的进程。纵向研究是该基金研究部分的主题。这个项目是我研究方法的延伸。将通过以疾病替代标志物作为终点的前瞻性集合队列的巢式病例对照分析来检验该假设。 目前，我在临床服务方面投入了45%的精力。K24以患者为导向的研究中期职业研究者奖将使我能够将患者护理责任减少到10%，因此我可以更加专注于培训下一代临床研究者。我将能够增加2倍的医生，我可以充分指导他们进行转化研究。K24奖的第二个目标是获得流行病学和生物统计学方面的重点培训。这种教学经验将加强我与生物统计学家的合作，并使我能够学习分析大型数据集所需的定量技术。K24还将支持与生物统计学家llana Belitskaya-Levy博士的合作，后者在分层聚类和艾滋病毒突变分析方面具有专业知识。我们将开发新的算法来对患者进行分层，并分析纵向资助过程中的病毒进化。K24奖提供的支持将增强我参与转化研究项目的潜力，这些项目旨在开发有效的新策略，以改善继发性肺部感染的HIV感染患者的护理。