Frailty is a complication of aging resulting from a dysregulation of multiple systems leading to increased morbidity, and ultimately increased mortality. The prevalence of frailty is 3-fold higher in human immunodeficiency virus type-1 (HIV-1) infected patients than age-matched HIV-negative controls, and occurs 20 years earlier than would be expected in HIV-1-negative aging patients. Preliminary analyses of ongoing studies of frailty by our group suggest a previously unrecognized association between immune activation, immune senescence, and clinical frailty in HIV-1-infected persons treated with highly-active antiretroviral therapy (HAART). The global aim of this proposal is to understand the mechanisms of immune dysfunction in HIV-1-infected frail individuals. To evaluate the global aim, we will use stored samples from HIV-1 infected frail individuals and matched HIV-1 infected non-frail controls to 1) Determine the role of chronic cytomegalovirus (CMV) co-infection in HIV-related frailty through CMV-antigen stimulation of T-cells 2) Investigate the role of microbial gut translocation in HIV-related frailty through plasma lipopolysaccharide (LPS) and soluble activation marker CD14 (sCD14) and 3) Use microarray analysis of human T-cell genes to identify potential gene expression patterns associated with the frail phenotype in HIV-1 infected persons. The proposed research will provide the first analysis of the role of chronic CMV infection, microbial translocation, and polymorphisms in T- cells in the development of HIV-1-related frailty. The results will have significant clinical implications in efforts to diagnose, treat, and prevent frailty in HIV-1-infected and uninfected individuals.

Public Health Relevance

The proposed research will provide the first analysis of the role of chronic CMV infection, microbial translocation, and polymorphisms in T-cells in the development of HIV-related frailty. The results will have significant clinical implications in efforts to diagnose, treat, and prevent frailty in HIV-infected and uninfected individuals.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Small Research Grants (R03)
Project #
5R03AG040594-02
Application #
8309033
Study Section
Special Emphasis Panel (ZAG1-ZIJ-9 (M1))
Program Officer
Eldadah, Basil A
Project Start
2011-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2012
Total Cost
$76,500
Indirect Cost
$26,500
Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
041096314
City
Aurora
State
CO
Country
United States
Zip Code
80045
Erlandson, Kristine M; O?Riordan, Maryann; Labbato, Danielle et al. (2014) Relationships between inflammation, immune activation, and bone health among HIV-infected adults on stable antiretroviral therapy. J Acquir Immune Defic Syndr 65:290-8
Erlandson, Kristine M; Schrack, Jennifer A; Jankowski, Catherine M et al. (2014) Functional impairment, disability, and frailty in adults aging with HIV-infection. Curr HIV/AIDS Rep 11:279-90
Erlandson, Kristine M; Allshouse, Amanda A; Jankowski, Catherine M et al. (2014) Relationship of physical function and quality of life among persons aging with HIV infection. AIDS 28:1939-43
Erlandson, Kristine M; Allshouse, Amanda A; Jankowski, Catherine M et al. (2013) Association of functional impairment with inflammation and immune activation in HIV type 1-infected adults receiving effective antiretroviral therapy. J Infect Dis 208:249-59