CFAR Awards

M. Bradley Drummond, MD, MHS

Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine

DNA Methylation in HIV Infection: A Mechanism of COPD Pathogenesis

M. Bradley Drummond, MD, MHS - Image

Emerging data suggest an increased prevalence of chronic obstructive pulmonary disease (COPD) in the HIV-infected population, although the mechanisms underlying this association are unclear.  Epigenetic regulation of gene expression through altered DNA methylation and histone acetylation has been implicated in COPD pathogenesis. It has also been shown that HIV infection impacts epigenetic regulation with altered downstream cytokine expression. Some of these cytokines are associated with COPD.  We have found that elevated plasma HIV viral levels are independently associated with an increased risk of COPD and with lung function decline, suggesting a link between uncontrolled HIV viremia and COPD pathogenesis. 

HIV-mediated epigenetic regulation of DNA targets implicated in COPD represents a potential mechanism for increased COPD risk in HIV-infected individuals.  To understand this relationship, it is necessary to first evaluate the effect of viral suppression on global DNA methylation patterns in the lung and blood of HIV-infected individuals.  Our overall hypothesis is that HIV infection alters genome-wide methylation patterns in the blood and lung compartments of smokers, and these patterns will be impacted following virological control associated with antiretroviral (ART) therapy.  To test this hypothesis, we will assess global methylation patterns in blood and bronchoalveolar (BAL) samples previously collected from HIV-infected smokers before initiation of HAART and after demonstrating viral suppression.  In addition to informing our initial understanding of how HIV viral levels impact epigenetic regulation of genes associated with COPD pathogenesis, the data obtained from this study will provide the requisite preliminary data to justify a larger study of methylation patterns and COPD within our larger HIV and lung disease cohort (Study of HIV Infection in the Etiology of Lung Disease).