HIV activation in secondary pulmonary infection

描述(由申请人提供)：我是一名临床调查员，对肺部感染的病理生物学有研究兴趣。我对通过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。这一方法卓有成效，在培训临床研究人员方面也很有效。最近由R01资助的一项研究名为“HIV相关细菌性肺炎的纵向研究”，我是该研究的联合PI。这项研究扩展了实验室调查细菌性肺炎的工作。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患者将继续发展为细菌性肺炎和其他肺部感染，这将导致肺部特有的细胞募集和激活。这一过程将促进艾滋病毒-1的复制和变异，加速艾滋病的进程。这项纵向研究是这笔赠款研究部分的主题。这个项目代表了我研究方法的延伸。这一假设将通过对以疾病替代标记物为终点的前瞻性队列进行嵌套病例对照分析来检验。 我目前在临床服务上花费了45%的精力。K24职业生涯中期研究人员奖将使我能够将患者护理责任减少到10%的努力，因此我可以将重点放在培训下一代临床调查人员上。我将能够将我可以在翻译研究中充分指导的医生数量增加两倍。K24奖项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量化技术。K24还将支持与Llana Belitskaya-Levy博士的合作，Llana Belitskaya-Levy博士是一名生物统计学家，在等级聚类和艾滋病毒突变分析方面具有专长。我们将开发新的算法来对患者进行分层，并分析纵向拨款过程中的病毒演变。K24奖项提供的支持将增强我参与转化研究项目的潜力，这些项目开发有效的、新颖的战略，以改善对患有继发性肺部感染的艾滋病毒感染患者的护理。

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.