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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
2K24AI108516-06
Application #
10083072
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Chiou, Chen-Chia Christine C
Project Start
2013-07-15
Project End
2025-06-30
Budget Start
2020-07-25
Budget End
2021-06-30
Support Year
6
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94118
Glesby, Marshall J; Hanna, David B; Hoover, Donald R et al. (2018) Abdominal fat depots, insulin resistance, and incident diabetes mellitus in women with and without HIV infection. AIDS 32:1643-1650
Sharma, Anjali; Ma, Yifei; Tien, Phyllis C et al. (2018) HIV Infection Is Associated With Abnormal Bone Microarchitecture: Measurement of Trabecular Bone Score in the Women's Interagency HIV Study. J Acquir Immune Defic Syndr 78:441-449
Kardashian, Ani; Ma, Yifei; Scherzer, Rebecca et al. (2017) Sex differences in the association of HIV infection with hepatic steatosis. AIDS 31:365-373
Reid, Michael; Price, Jennifer C; Tien, Phyllis C (2017) Hepatitis C Virus Infection in the Older Patient. Infect Dis Clin North Am 31:827-838
Price, Jennifer C; Dodge, Jennifer L; Ma, Yifei et al. (2017) Controlled attenuation parameter and magnetic resonance spectroscopy-measured liver steatosis are discordant in obese HIV-infected adults. AIDS 31:2119-2125
Imp, Brandon M; Rubin, Leah H; Tien, Phyllis C et al. (2017) Monocyte Activation Is Associated With Worse Cognitive Performance in HIV-Infected Women With Virologic Suppression. J Infect Dis 215:114-121
Reid, Michael; Ma, Yifei; Scherzer, Rebecca et al. (2017) Higher CD163 levels are associated with insulin resistance in hepatitis C virus-infected and HIV-infected adults. AIDS 31:385-393
Price, Jennifer C; Ma, Yifei; Scherzer, Rebecca et al. (2017) Human immunodeficiency virus-infected and uninfected adults with non-genotype 3 hepatitis C virus have less hepatic steatosis than adults with neither infection. Hepatology 65:853-863
Seang, Sophie; Lake, Jordan E; Tian, Fang et al. (2016) Oral Glucose Tolerance Testing identifies HIV+ infected women with Diabetes Mellitus (DM) not captured by standard DM definition. J AIDS Clin Res 7:
Swanson, Sophia; Ma, Yifei; Scherzer, Rebecca et al. (2016) Association of HIV, Hepatitis C Virus, and Liver Fibrosis Severity With the Enhanced Liver Fibrosis Score. J Infect Dis 213:1079-86

Showing the most recent 10 out of 19 publications