HIV activation in secondary pulmonary infection

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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.