Johns Hopkins University

Johns Hopkins University

Inclusion/Exclusion CriteriaPopulation Overview

Principal Investigator: Gregory Kirk (
Co-Principal Investigator: John McDyer (

HIV-infected persons appear to be at higher risk for chronic obstructive pulmonary disease (COPD), although the clinical manifestations and underlying mechanisms of HIV-associated COPD remain unclear. The ongoing Study of HIV Infection in the Etiology of Lung Disease (SHIELD) cohort has recruited >2,000 participants to prospectively evaluate how HIV infection may enhance susceptibility to COPD. SHIELD data suggest that poorly controlled plasma HIV viremia accelerates lung function decline. Further, HIV-associated COPD is characterized by CD4+ T cell depletion occurring to a greater extent in the lung mucosa than in the periphery. Based on these findings, our central hypothesis is that the development and clinical manifestations of HIV- associated COPD are driven, at least in part, by HIV viral replication, CD4+ T cell depletion and CD8+ T cell immune activation in the lung mucosa, and this immune dysregulation is associated with specific clinical phenotypes.

Our multidisciplinary team of investigators provides clinical and research expertise in HIV, pulmonary diseases, and immunology, and have an established track record of productive collaboration in HIV and COPD. SHIELD provides an ideal study population and research infrastructure to perform these clinical and mechanistic studies. In summary, this proposal directly addresses critical gaps in our understanding of the clinical spectrum and consequences of HIV-associated COPD and will identify key biologic mechanisms contributing to the disease. Findings will inform the clinical management and development of interventions targeting HIV- associated COPD, and may also inform broader strategies for COPD in non-HIV infected populations.

Specific Aims
(1) To characterize phenotypes of HIV-associated compared to HIV-negative COPD, and to define the clinical and patient-reported consequences of these phenotypes.
(2) To test the hypothesis that the presence and severity of HIV-associated COPD is correlated with progressive lung mucosal CD4+ T cell depletion.
(3) To test the hypothesis that lung mucosal CD4+ T cells are depleted and dysregulated in HIV-associated COPD due to HIV replication.
(4) To test the hypothesis that there is increased lung CD8+ T cell activation in HIV-associated COPD due to the loss of CD4+ T cell regulatory mechanisms.

Study Design: Longitudinal and cross-sectional
Available Biospecimens: Plasma, serum, BAL (cellular), PBMC (viable, pellets)