Project Summary
Cardiovascular disease (CVD) remains the leading cause of mortality in women, with approximately
one woman dying per minute in the US. Women living with HIV (WLHIV) are a particularly high-risk group
of women with high CVD prevalence who have long been understudied in clinical research. As compared
with uninfected women, WLHIV have a 2 to 4-fold increased CVD risk that persists later life and which is on
par with men living with HIV. Additional research on sex-specific mechanisms of HIV-associated CVD will
better inform the development of CVD prevention and treatment approaches clinically relevant to over 16
million women with HIV globally. Current CVD treatment approaches for PWH are lacking and have
focused on applying cardiology guidelines from the general non-HIV population to PWH, however
traditional risk assessments tend to underestimate CVD risk, possibly due to higher levels of chronic
inflammation recognized in PWH, and pronounced in WLHIV. Initial work performed in the Hays lab
demonstrated that nitric-oxide mediated coronary endothelial dysfunction, which contributes to
atherosclerosis and predicts adverse cardiovascular events, is present at early ages in women and men
with HIV compared to age-matched control participants without HIV. During the course of our initial work,
we identified emerging risk markers in women and men with HIV such as abnormal fat distribution and
associated inflammation, lipoprotein metabolism, and early menopause (in women) which may contribute
to early impaired CEF. However, these early studies were cross-sectional in nature, and it is unclear how
these important risk markers influence vascular health over time in women compared to men with HIV.
The goal of the Hays lab over the next few years will be to: 1) better understand contributors and sex-
specific pathways that underlie progression of heart disease in PWH with a focus on the role of ectopic fat
deposition on long term vascular endothelial health 2) to evaluate and test novel risk markers (both
targeted and untargeted markers using proteomics) for sex-specific CVD risk in PWH and 3) identify
potential treatment targets that may be rapidly translated and tested in clinical trials in PWH. For the first
two goals, we propose a longitudinal study with equal numbers of men and women with HIV across the
lifespan to test the hypothesis that a hyperinflammatory milieu characterized by abnormal fat distribution,
increased systemic inflammation and abnormal lipoprotein levels result in worsening CEF over time in
PWH. The identification of important biologic drivers of increased CV risk in PWH is critical to define new
therapeutic approaches. We will also study glucagon-like peptide-1 receptor agonists (GLP-1RA) that may
reduce ectopic fat and slow the progression of CVD in PWH. My research program will address significant
knowledge gaps regarding sex-specific factors that affect vascular health in PWH and provide data to
design future interventional studies to improve health outcomes in PWH and cardiometabolic disorders.