HIV activation in secondary pulmonary infection

继发性肺部感染中的 HIV 激活

• 批准号: 8111269
• 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: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8111269
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adherence; Affect; Africa South of the Sahara; Age-Years; Alveolar; Alveolar Macrophages; Alveolitis; Anti-Retroviral Agents; Autopsy; Bacterial Pneumonia; Biological Assay; Biological Models; Blood; Bronchoalveolar Lavage; CD4 Lymphocyte Count; CD8B1 gene; CXCL10 gene; California; Caring; Cell Proliferation; Cells; Cessation of life; Characteristics; Chest; Chronic Disease; Clinical; Clinical Investigator; Clinical Services; Collaborations; Data Set; Diagnosis; Disease; Drug usage; Enrollment; Epidemic; Epidemiologist; Evolution; Fever; Flow Cytometry; Frequencies; Funding; Genetic Transcription; Goals; Grant; Granulomatous; HIV; HIV Infections; HIV Seropositivity; HIV-1; Heterosexuals; Highly Active Antiretroviral Therapy; Home environment; Homosexuals; Immune; Immunity; Individual; Infection; Infectious Disease Epidemiology; Infiltration; Inflammation; Inflammatory; Injection of therapeutic agent; Interleukin-15; Kaposi Sarcoma; Laboratories; Lead; Learning; Leukocytes; Life; Liquid substance; Longitudinal Studies; Lung; Lymphatic Diseases; Mediating; Medical; Memory; Mentors; Meta-Analysis; Mid-Career Clinical Scientist Award (K24); Midcareer Investigator Award in Patient-Oriented Research; Molecular; Morbidity - disease rate; Mutation; National Heart, Lung, and Blood Institute; New York; North America; Opportunistic Infections; Pathogenesis; Patient Care; Patients; Persons; Pharmaceutical Preparations; Physicians; Plasma; Pneumocystis carinii; Pneumonia; Population; Process; Production; Prophylactic treatment; Prospective Studies; Pulmonary function tests; Questionnaires; Recruitment Activity; Regulatory T-Lymphocyte; Reporting; Research; Research Personnel; Research Subjects; Rest; Risk; Sampling; Sarcoidosis; Sentinel; Site; South Africa; Specimen; Surface; Syndrome; T-Cell Activation; T-Cell Development; T-Lymphocyte; Techniques; Tissues; Training; Translational Research; Tuberculosis; Universities; V3 Loop; Variant; Viral; Viral Load result; Virus; Western Europe; Work; antiretroviral therapy; cell motility; chemokine; cohort; cytokine; experience; improved; interest; interstitial; macrophage; men; mortality; next generation; novel strategies; peripheral blood; programs; reconstitution; respiratory; response; sex; transmission process

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. My research is supported by 2 R01 grants. "HIV/TB Interaction in the Lung" investigates the hypothesis that resting alveolar macrophages express a set of transcriptional repressers that normally inhibit HIV replication in the lung. During tuberculosis (TB), inflammatory cells are recruited to the lung, contact macrophages, and derepress the HIV-1 LTR. Soluble factors from the inflammatory cells then activate transcription. This 2-step process is necessary and sufficient for the high-level replication of HIV-1 observed in persons with TB. A second 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 second 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. 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 training in infectious diseases epidemiology and matriculate in the MPH program at Columbia University. This didactic experience will enhance my collaboration with epidemiologists and will allow me to learn the quantitative techniques required to analyze large data sets. 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，研究方向是肺部感染的病理生物学。我对支气管肺泡灌洗获得的临床样本进行分子分析，然后在模型系统中进行机制研究。这种方法在培训临床研究人员方面是卓有成效的。我的研究得到了2r01基金的支持。“肺中的HIV/TB相互作用”研究了静息肺泡巨噬细胞表达一组转录抑制因子的假设，这些转录抑制因子通常会抑制HIV在肺中的复制。在结核病（TB）期间，炎症细胞被招募到肺部，与巨噬细胞接触，并抑制HIV-1 LTR，炎症细胞中的可溶性因子随后激活转录。这两步过程对于在结核病患者中观察到的HIV-1高水平复制是必要和充分的。另一项最近由r01资助的研究，我是该项研究的共同负责人，名为“hiv相关细菌性肺炎的纵向研究”。本研究扩展了实验室研究细菌性肺炎的工作。第二项研究的假设是，接受抗逆转录病毒治疗的hiv阳性个体将继续发展为细菌性肺炎和其他肺部感染，这将导致肺部特征性的细胞募集和激活。这一过程将增强HIV-1的复制和突变，加速艾滋病的进程。纵向研究是本基金研究部分的主题。目前我有45%的精力放在临床服务上。K24面向患者研究的职业中期研究者奖将使我能够将患者护理责任减少到10%的努力，因此我可以将我的重点放在培养下一代临床研究者上。我将能够增加两倍的医生数量，我可以在转化研究中充分指导他们。K24奖的第二个目标是获得传染病流行病学方面的培训，并进入哥伦比亚大学的公共卫生硕士项目。这种教学经验将加强我与流行病学家的合作，并使我能够学习分析大型数据集所需的定量技术。K24奖提供的支持将增强我参与转化研究项目的潜力，为改善继发性肺部感染的hiv感染者的护理制定有效的新策略。