I am an internist trained in infectious disease and HIV epidemiology, whose research is focused on HIV and HCV infections. Since joining the faculty at the University of California, San Francisco (UCSF) in 2000, I have developed a nationally recognized clinical translational research program focused on understanding the associations of HIV infection and HCV infection with adipose tissue changes, and metabolic and inflammatory perturbations, including hepatic steatosis (or fatty liver disease). My currently supported research includes: 1) an R01 that establishes a cohort of mainly 300 men with HIV and HCV monoinfection, HIV/HCV coinfection and those with neither infection to determine the effects of visceral adiposity, HIV, HCV and their metabolic and inflammatory consequences on fatty liver disease (VAHH Study); and 2) a U01 in a large prospective cohort of women with and at risk for HIV (Women's Interagency HIV Study [WIHS]) that has a core goal to determine the contribution of HIV, host immune mechanisms, behavioral and cardiovascular risk factors to organ injury. Data from the Study of Fat Redistribution and Metabolic Change in HIV infection (FRAM) also is available to me. Within this framework, I propose to expand my research agenda to: (1) investigate the contribution of HIV, HCV, and their metabolic and inflammatory consequences to long term outcomes including liver disease progression measured using novel non-invasive techniques, as well as osteoporosis and vascular disease; (2) determine sex differences in the association of HIV, HCV, and their metabolic and inflammatory consequences with long term outcomes (by pooling the detailed outcomes data collected from WIHS women and VAHH and FRAM men and women) and how the menopausal transition may further alter these relationships in women compared to men; and (3) use the results to define sex-specific mechanisms that will enable interventional studies that take into account sex effects in the pathogenesis of these outcomes in HIV-infected and HCV-infected persons. With access to the broad range of rigorously collected measurements from these three cohorts (including measurement of liver fibrosis by ultrasound based transient elastography, hepatic steatosis and visceral adipose tissue by MRI, bone mineral density by Dual Energy X-Ray Absorptiometry scans, and carotid intima media thickness by ultrasound), I propose to expand my mentoring program to mentees with an interest in HIV and HCV infections from a multitude of disciplines including infectious diseases, hepatology, endocrinology and metabolism, cardiology, and radiology. The ability to bring in mentees from disciplines outside of infectious diseases will further enrich my research program. I plan to also seek additional training in professional leadership and how to build a structured and sustainable mentoring program in order to develop the next generation of clinical investigators in HIV and HCV research, and to ensure that they will ultimately become skilled mentors themselves.

Public Health Relevance

As the proportion of U.S. HIV-infected men and women over the age of 50 years increases to over 50% by the year 2015, it will be of critical importance to understand the influence of HIV infection, HCV infection, the menopausal transition and their associated immune and metabolic perturbations to changes in the trajectory of liver, bone, and vascular injury. Dr. Tien proposes to expand her research program to investigate long term organ injury by building collaborations with mentees across a range of disciplines (e.g. hepatology, endocrinology, and cardiology) and seeking additional training in mentoring and professional leadership development. Together they will enrich her research program and develop the next generation of clinical investigators in high priority HIV and HCV 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 #
5K24AI108516-03
Application #
8875588
Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
Chiou, Chen-Chia (Christine) C
Project Start
2013-07-15
Project End
2016-06-30
Budget Start
2015-07-01
Budget End
2016-06-30
Support Year
3
Fiscal Year
2015
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

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