Mentoring in Sex and Gender-informed Multidisciplinary Research on Cardiometabolic Comorbidities in Persons with HIV

Emory University, Atlanta GA

Investigators

Abstract

PROJECT SUMMARY/ABSTRACT Cardiovascular disease (CVD) accounts for significant morbidity and mortality among persons living with HIV (PWH) on antiretroviral therapy (ART). Compared to HIV-seronegative individuals, PWH experience higher risk of acute myocardial infarction, sudden cardiac death, and progression of subclinical carotid atherosclerosis; further, women with HIV have a higher relative risk of CVD compared to men with HIV. Viral- induced inflammation and immune activation play a prominent role in increased CVD risk among PWH. HIV persistence due to latent reservoirs in the periphery and the gut is suspected to contribute to this inflammation. However, our understanding of the underlying pathophysiologic mechanisms of cardiometabolic diseases in PWH is limited; similarly, whether these mechanisms differ by sex has yet to be elucidated. With women accounting for >50% of an aging global HIV population, it is critical to train the next generation of HIV scientists to become leaders in sex and gender-informed HIV cardiometabolic comorbidity research. As an Associate Professor of Medicine in the Emory Division of Infectious Diseases, my NIH-funded research and successful mentorship program over the last decade has examined factors that contribute to obesity and cardiometabolic comorbidities in the setting of chronic HIV with a focus on women and sex differences. Leveraging tight collaborations with experts in high-resolution metabolomics (HRM), lipidomics, HIV persistence, and T cell immunology as well as an established longitudinal cohort of PWH with >50% representation of women and detailed HIV reservoir and subclinical CVD profiling, two new research aims are proposed: 1) Assess relationships between the metabolome, lipidome, HIV reservoir, and subclinical CVD by sex, and 2) Determine sex-specific multi-omic signatures associated with an increased risk of subclinical CVD by HIV reservoir size. Through this K24 award, my specific career objectives are to 1) enhance my knowledge of lipidomic and HRM methodologies to identify markers of CVD risk in persons with HIV (AIM 1); 2) increase my understanding of multi-omics integration analyses to uncover mechanisms driving CVD (AIM 2); 3) expand my understanding of the intersection of sex and gender science (all AIMS), and 4) improve the structure and quality of my patient-oriented research mentoring program. The proposed new research and training plan would provide essential insight into the use of HRM, lipidomic and multi-omic integrative analyses to increase our understanding of relationships between the HIV reservoir and development of CVD in PWH by sex. These new methodologic skills would enhance my current research program and career development, provide robust training opportunities for mentees, and advance the development of new preventative strategies to reduce the burden of CVD among PWH.