PROJECT ABSTRACT I am a Professor of Medicine trained in infectious diseases (ID) and HIV epidemiology, who has developed a nationally recognized clinical translational research program focused on understanding the associations of HIV and HCV infection with adipose tissue changes, and metabolic and inflammatory perturbations, and their effects on long-term organ injury (liver, bone, and vascular). My current supported research includes: 1) a R01 that establishes a longitudinal multisite cohort of ~1500 women with HIV and/or HCV infection, and those with neither infection to determine the effects of HIV, HCV, and gonadal aging on liver steatosis and fibrosis progression using FibroScan®; 2) a second R01 and a Merck investigator-initiated award that examines the effects of HCV cure and: a) latent HIV reservoirs, immune activation, and liver fibrosis and b) novel biomarkers of kidney injury in persons treated with direct acting antiviral agents; 3) a second Merck award that examines the association of plasma levels of integrase strand inhibitors (INSTIs) with body composition changes; and 4) a U01 whose core goal is to study the long-term progression of HIV in U.S. men and women from the Multicenter AIDS Cohort Study (MACS) and the Women’s Interagency HIV Study (WIHS). My research grants leverage the infrastructure of the WIHS, which in 2019 became the MACS-WIHS Combined Cohort Study (MWCCS). For the new research to be supported by the K24 renewal, I will augment our current sample of women with ~3000 MWCCS men who will undergo FibroScan® beginning in 2020 to: 1) examine how health-related disparities (socioeconomic, behavioral and mental health conditions, i.e. income, education, region/neighborhood of residence, healthcare access, food security, and depression), biologic sex including gonadal aging, and ancestry informative markers influence steatosis and fibrosis progression; 2) investigate the biologic and immune pathways associated with steatosis and fibrosis progression using objective measurement of visceral adiposity, sex hormone levels, gut and oral microbiome analysis, plasma and hair INSTI levels obtained in the MWCCS; 3) determine how steatosis and fibrosis affects extrahepatic outcomes (cardiac, neurocognition, bone). The proposed studies will expand my research portfolio and extend the depth of my mentoring program to include mentees from an array of new disciplines (e.g. socio-behavioral sciences, endocrinology, pharmacology, and microbiology, in addition to mentees in ID, hepatology, and cardiology), and mentees from underrepresented minority (URM) groups who can effectively contribute to the HIV communities most at risk today. The MWCCS provides mentees with ready access to a rich research platform to build their careers in patient-oriented research. I plan additional training in professional and diversity leadership and how to build a structured and sustainable mentoring program in order to develop early and mid-career investigators (especially URM investigators) in HIV research, and to ensure that they will ultimately become skilled mentors themselves.

PROJECT NARRATIVE With over half of men and women living with HIV now over the age of 50 years and new HIV infections mainly in minority populations, it will be of critical importance to understand the influence of health disparities (socioeconomic and behavioral conditions by biologic sex and race/ethnicity) and biologic processes (gonadal aging, adiposity, immune perturbation) on fatty liver disease and its clinical sequelae (cardiac, neurocognitive, and bone injury) in persons with HIV and HCV infection in the current era of anti‐viral treatment. I propose to expand my research program by building collaborations with mentees across a range of disciplines (e.g. hepatology, endocrinology, cardiology, neuropsychology, immunology, pharmacology) and prioritizing mentorship of underrepresented minority investigators who can effectively contribute to the HIV communities most at risk today. Together they will enrich my research program and develop the next generation of clinical investigators in high priority HIV research.