PROJECT SUMMARY
Today, persons living with HIV (PLWH) face a disproportionate burden of chronic respiratory disease and
accelerated lung aging. Despite advances in research that have increased our understanding of lung disease
among PLWH, there are significant gaps in our knowledge of factors that impact lung health in this at-risk
population. Worldwide ambient air pollution remains a significant, but modifiable, contributor to chronic
respiratory morbidity and disease development. While translational studies suggest that HIV increases
susceptibility to cigarette smoke, whether this applies to long-term ambient air pollution exposure has not been
studied. To date, the impact of long-term air pollution exposure on lung aging in HIV remains unknown. The
Study of HIV Infection in the Etiology of Lung Disease (SHIELD), a prospective cohort of 2600 individuals with
or at-risk for HIV in Baltimore, MD, provides an ideal platform to efficiently answer questions about the impact of
the environment on lung aging for PLWH. Building on the existing SHIELD cohort, we aim to determine if
long-term ambient air pollution is a driver of accelerated lung aging in a high-risk population, and if
PLWH are more susceptible to the respiratory health effects of pollutant exposure.
The proposed research will uniquely characterize the interaction between the environment, HIV, and lung aging.
We will add refined measures of long-term ambient air pollution with enhanced precision, in-depth CT
phenotyping to capture early lung disease, and molecular markers of biologic aging and susceptibility to
exposures, while leveraging longitudinal lung function data from a well-defined cohort of PLWH. We propose
three aims to study the impact of long-term exposures on multidimensional (physiologic, radiographic, and
biologic) lung aging among PLWH. (Aim 1) To determine the association between long-term ambient pollutant
exposure and physiologic lung aging (trajectory of lung function decline) and health related quality of life for
PLWH and comparable HIV-uninfected participants; (Aim 2) To define the impact of long-term pollutant exposure
on CT measures of radiographic lung aging (small airways disease, air trapping, emphysema) among PLWH;
(Aim 3) To determine the association between long-term pollutant exposure and accelerated “biologic” aging,
measured via the epigenetic clock, a molecular marker of biologic responses and susceptibility to pollutant
exposure. In all aims we will examine how HIV and markers of HIV control increase susceptibility to air pollution.
This proposal will provide mentored training in the implementation of an environmental cohort study, the
complexities of HIV-lung disease research, advanced biostatical methods, novel CT analysis techniques for lung
phenotyping, and the application of epigenetic markers to describe biologic responses and susceptibility to
exposures. The career development plan includes expert mentorship, formal coursework, and hands-on
experience to facilitate Dr. Raju in achieving his career goal of becoming an independent physician scientist with
expertise at the intersection of environmental health disparities, HIV, and lung health research.