Predictable declines in lung function occur with age, but the impact of aging with HIV on lung function remains largely unexplored. The Study of HIV Infection in the Etiology of Lung Disease (SHIELD) is an ongoing, prospective cohort of individuals with or at-risk for HIV that seeks to understand how HIV may impact lung function. SHIELD data indicate that HIV-infected persons have lower baseline lung function, measured as the forced expiratory volume in 1 second (FEV1), and that poorly controlled HIV plasma viremia is strongly associated with accelerated FEV1 decline over three years. We hypothesize that at older ages, HIV may accelerate the age-related decline in lung function, even among persons with well-controlled HIV disease, resulting in adverse clinical, functional and patient-reported outcomes. Further, we hypothesize that this process is driven at least in part by systemic inflammation and manifests with elastin degradation. By extending follow-up with regular interviews, spirometry, and blood collection on ~2000 well-characterized participants, SHIELD will accrue a decade of data, samples and endpoints allowing rigorous investigation of HIV, aging and lung function. We propose to systematically characterize the rates and predictors of lung function decline in our aging population of HIV-infected and comparable HIV-uninfected persons (Aim 1), to define the adverse clinical, functional, and patient-reported consequences associated with rapid lung function decline (Aim 2), and to delineate the contribution of systemic inflammation and elastin degradation to rapid lung function decline (Aim 3). Findings from the successful completion of these Aims will inform strategies for improving clinical management, developing interventions to slow lung function decline, and improving the healthy aging of persons living with HIV infection.

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HIV infection appears to accelerate the age-related decline in lung function. By extending follow-up of a large well-characterized cohort of HIV-infected and comparable HIV-uninfected persons, this proposal will significantly advance our understanding of accelerated lung aging in HIV infection, identifying key risk factors, defining related consequences, and elucidating underlying mechanisms.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Special Emphasis Panel (ZHL1)
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Caler, Elisabet V
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Johns Hopkins University
Public Health & Prev Medicine
Schools of Public Health
United States
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Shiels, Meredith S; Kirk, Gregory D; Drummond, M Bradley et al. (2018) HIV Infection and Circulating Levels of Prosurfactant Protein B and Surfactant Protein D. J Infect Dis 217:413-417
Drummond, M Bradley; Lambert, Allison A; Hussien, Amira F et al. (2017) HIV Infection Is Independently Associated with Increased CT Scan Lung Density. Acad Radiol 24:137-145
Walker-Sperling, Victoria E; Merlo, Christian A; Buckheit 3rd, Robert W et al. (2016) Short Communication: HIV Controller T Cells Effectively Inhibit Viral Replication in Alveolar Macrophages. AIDS Res Hum Retroviruses 32:1097-1099
Popescu, Iulia; Drummond, M Bradley; Gama, Lucio et al. (2016) HIV Suppression Restores the Lung Mucosal CD4+ T-Cell Viral Immune Response and Resolves CD8+ T-Cell Alveolitis in Patients at Risk for HIV-Associated Chronic Obstructive Pulmonary Disease. J Infect Dis 214:1520-1530
Leader, Joseph K; Crothers, Kristina; Huang, Laurence et al. (2016) Risk Factors Associated With Quantitative Evidence of Lung Emphysema and Fibrosis in an HIV-Infected Cohort. J Acquir Immune Defic Syndr 71:420-7
Brune, Kieran A; Ferreira, Fernanda; Mandke, Pooja et al. (2016) HIV Impairs Lung Epithelial Integrity and Enters the Epithelium to Promote Chronic Lung Inflammation. PLoS One 11:e0149679
Lambert, Allison A; Drummond, M Bradley; Kisalu, Annamarie et al. (2016) Implementation of a COPD Screening Questionnaire in an Outpatient HIV Clinic. COPD 13:767-772
Drummond, M Bradley; Kunisaki, Ken M; Huang, Laurence (2016) Obstructive Lung Diseases in HIV: A Clinical Review and Identification of Key Future Research Needs. Semin Respir Crit Care Med 37:277-88
Lambert, Allison A; Kirk, Gregory D; Astemborski, Jacquie et al. (2015) HIV Infection Is Associated With Increased Risk for Acute Exacerbation of COPD. J Acquir Immune Defic Syndr 69:68-74
Drummond, M Bradley; Huang, Laurence; Diaz, Philip T et al. (2015) Factors associated with abnormal spirometry among HIV-infected individuals. AIDS 29:1691-700

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