This application addresses broad Challenge Area (05) Comparative Effectiveness Research and specific Challenge Topic, 05-AI-101: Accelerated Aging in Treated vs. Untreated HIV/AIDS. With the advent of HAART, life expectancy for HIV-infected persons may now extend for decades. As growing numbers of HIV-infected persons in the US are surviving into older ages, a shifting spectrum of disease towards age-associated non- AIDS conditions has been documented and an accelerated aging process has been hypothesized. Proposed is systematic investigation of the epidemiology and mechanisms of declines in physical function and of the development of frailty, recognized phenotypes for the aging process. Using longitudinal data collected in the AIDS Linked to the IntraVenous Experience (ALIVE) study for up to 7 years, we will define trajectories and identify demographic, behavioral, and clinical correlates of physical function decline and a frailty-related phenotype. Utilizing our extensive biological repository and building on prior mechanistic work which identified selected inflammatory genes involved in frailty, we will evaluate circulating inflammatory markers and inflammatory gene expression levels in participants with or without physical function declines using a nested case-control study design. We emphasize the evaluation of HAART, particularly the comparative effect of treatment interruptions or incomplete virologic suppression versus continuous or suppressive therapy respectively, in predicting decrements or improvements in physical function. The community-recruited ALIVE cohort represents an urban, predominantly African American population of both genders with significant risk factors for chronic diseases. Importantly, ALIVE includes at risk HIV-uninfected participants, providing an epidemiologically-appropriate comparison group to permit HIV-related effects on aging phenotypes to be separated from background effects among high-risk persons. Our proposal, which largely supports the immediate hiring of new personnel, represents an efficient, value-added research investment by performing highly focused investigations on participants nested within an existing HIV cohort. Results from these studies will inform the HIV research community on the rates of, predictors and mechanisms involved in physical function declines, which may eventually allow earlier identification and intervention to prevent accelerated aging among HIV-infected persons.

Public Health Relevance

This application addresses broad Challenge Area (05) Comparative Effectiveness Research and specific Challenge Topic, 05-AI-101: Accelerated Aging in Treated vs. Untreated HIV/AIDS.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
NIH Challenge Grants and Partnerships Program (RC1)
Project #
1RC1AI086053-01
Application #
7814138
Study Section
Special Emphasis Panel (ZRG1-BBBP-L (58))
Program Officer
Huebner, Robin E
Project Start
2009-09-24
Project End
2011-08-31
Budget Start
2009-09-24
Budget End
2010-08-31
Support Year
1
Fiscal Year
2009
Total Cost
$498,606
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Public Health
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Piggott, Damani A; Muzaale, Abimereki D; Varadhan, Ravi et al. (2017) Frailty and Cause-Specific Hospitalization Among Persons Aging With HIV Infection and Injection Drug Use. J Gerontol A Biol Sci Med Sci 72:389-394
Kirk, Gregory D; Dandorf, Stewart; Li, Huifen et al. (2017) Differential Relationships among Circulating Inflammatory and Immune Activation Biomediators and Impact of Aging and Human Immunodeficiency Virus Infection in a Cohort of Injection Drug Users. Front Immunol 8:1343
Pavasini, Rita; Guralnik, Jack; Brown, Justin C et al. (2016) Short Physical Performance Battery and all-cause mortality: systematic review and meta-analysis. BMC Med 14:215
Piggott, Damani A; Varadhan, Ravi; Mehta, Shruti H et al. (2015) Frailty, Inflammation, and Mortality Among Persons Aging With HIV Infection and Injection Drug Use. J Gerontol A Biol Sci Med Sci 70:1542-7
Leng, Sean X; Dandorf, Stewart; Li, Huifen et al. (2015) Associations of Circulating Soluble Tumor Necrosis Factor-? Receptors 1 and 2 with Interleukin-6 Levels in an Aging Cohort of Injection Drug Users with or at High Risk for HIV Infection. AIDS Res Hum Retroviruses 31:1257-64
Greene, Meredith; Covinsky, Kenneth; Astemborski, Jacquie et al. (2014) The relationship of physical performance with HIV disease and mortality. AIDS 28:2711-9
Salter, Megan L; Lau, Bryan; Mehta, Shruti H et al. (2013) Correlates of elevated interleukin-6 and C-reactive protein in persons with or at high risk for HCV and HIV infections. J Acquir Immune Defic Syndr 64:488-95
Piggott, Damani A; Muzaale, Abimereki D; Mehta, Shruti H et al. (2013) Frailty, HIV infection, and mortality in an aging cohort of injection drug users. PLoS One 8:e54910
Estrella, Michelle M; Kirk, Gregory D; Mehta, Shruti H et al. (2012) Vitamin D deficiency and persistent proteinuria among HIV-infected and uninfected injection drug users. AIDS 26:295-302
Salter, Megan L; Lau, Bryan; Go, Vivian F et al. (2011) HIV infection, immune suppression, and uncontrolled viremia are associated with increased multimorbidity among aging injection drug users. Clin Infect Dis 53:1256-64

Showing the most recent 10 out of 12 publications