HIV activation in secondary pulmonary infection

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。最近有一项由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。本研究的假设是，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。这个项目是我研究方法的延伸。该假设将通过以疾病替代标志物为终点的前瞻性队列的嵌套病例对照分析来验证。

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.