The life expectancy of adults receiving antiretroviral therapy (ART) has been increasing progressively. By 2015 one-half of HIV+ people in the U.S. will be over age 50, and this number is expected to continue to rise. While there has been a growing interest in aging with HIV, there is a dearth of research on successful aging with HIV. We define successful aging as a multi-dimensional construct with physical, cognitive, and psychosocial domains, with the downstream outcome being self-perceived successful aging. The proposed study will be the first large-scale investigation examining the relationship of positive psychological factors such as resilience, hardiness, optimism, and social engagement along with laboratory-based systemic markers of biological aging and HIV disease severity to the different domains of successful aging in HIV+ individuals as compared to well- matched Non-HIV-infected Comparison subjects (NCs). Subjects will include 120 HIV+ adults and 90 NCs aged 36-65 years. The biomarkers will include: telomere length, F2-isoprostanes, inflammatory markers (high- sensitivity C-reactive protein, IL-6, d-dimer, TNF-alpha, CCL2, d-dimer and sCD14), insulin resistance, and allostatic load, and, among HIV+ individuals, indicators of HIV disease severity (plasma HIV viral load, CD4+ T-cell count, AIDS/nonAIDS). Participants in each decade (36-45, 46-55, 56-65) will be evaluated using a structured Multi-cohort Longitudinal Design (sMLD), with balanced recruitment providing 40 HIV+ and 30 HIV- subjects per decade. The sMLD enables separation of cohort effects from developmental (within-subject) aging effects, allowing us to estimate aging trajectories across the entire age range of 36-65 years. Subjects will be followed for up to 4 years, with in-person bi-annual visits for detailed assessments, and evaluated with follow- up telephone interviews and mail surveys in the years in which they are not seen in person. We will examine the longitudinal trajectories of clinical outcome measures and positive psychological factors as well as biomarkers of aging and HIV disease, and compare them to those in NC subjects.
Our first aim i s to determine whether and how trajectories of successful aging differ between HIV+ and NC groups. We will also identify predictors of successful aging trajectories in HIV+ and NC groups. This project is related to NIMH Strategic Objective #2: charting illness trajectories to determine when, where, and how to intervene with HIV+ individuals. This study is novel in its focus on multi-dimensional characterization and recognition of predictors of successful aging in HIV+ adults as well as the use of advanced statistical methodology that allows for the distinction of cohort and developmental aging effects. We anticipate that successful aging trajectories will differ between HIV+ and NC groups suggesting that successful aging paradigms established in non-HIV-infected cannot be simply be generalized to HIV-infected persons. Understanding potentially malleable protective versus risk factors at an individual level may lead to development of new interventions aimed at increasing the likelihood of successful aging among people living with HIV.

Public Health Relevance

HIV is a serious, chronic, medical disease that affects the lives of more than one million Americans, with half of these individuals being older than 50 years. The goals of the proposed study are to determine the positive psychosocial factors such as resilience, hardiness, optimism, and social engagement as well as biomarkers of aging and of severity of HIV disease that predict physical, cognitive, and psychosocial aging along with self- perceived successful aging in HIV+ individuals compared to non-HIV+ adults. Understanding factors that promote successful aging at an individual level may lead to the development of new preventive and therapeutic interventions aimed at improving quality of life and well-being in adults with HIV.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH099987-03
Application #
8786910
Study Section
Behavioral and Social Consequences of HIV/AIDS Study Section (BSCH)
Program Officer
Brouwers, Pim
Project Start
2013-01-09
Project End
2017-12-31
Budget Start
2015-01-01
Budget End
2015-12-31
Support Year
3
Fiscal Year
2015
Total Cost
$639,049
Indirect Cost
$223,443
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Moore, Raeanne C; Hussain, Mariam A; Watson, Caitlin W-M et al. (2018) Grit and Ambition are Associated with Better Neurocognitive and Everyday Functioning Among Adults Living with HIV. AIDS Behav 22:3214-3225
Marquine, María J; Flores, Ilse; Kamat, Rujvi et al. (2018) A composite of multisystem injury and neurocognitive impairment in HIV infection: association with everyday functioning. J Neurovirol 24:549-556
Moore, David J; Fazeli, Pariya L; Moore, Raeanne C et al. (2018) Positive Psychological Factors are Linked to Successful Cognitive Aging Among Older Persons Living with HIV/AIDS. AIDS Behav 22:1551-1561
Rubtsova, Anna A; Marquine, María J; Depp, Colin et al. (2018) Psychosocial Correlates of Frailty Among HIV-Infected and HIV-Uninfected Adults. Behav Med :1-11
Oppenheim, Hannah; Paolillo, Emily W; Moore, Raeanne C et al. (2018) Neurocognitive functioning predicts frailty index in HIV. Neurology 91:e162-e170
Sakoda, Marissa E; Fazeli, Pariya L; Ellis, Ronald J et al. (2017) Higher Cystatin C Levels Are Associated With Neurocognitive Impairment in Older HIV+ Adults. J Acquir Immune Defic Syndr 74:243-249
Montoya, Jessica L; Iudicello, Jennifer; Oppenheim, Hannah A et al. (2017) Coagulation imbalance and neurocognitive functioning in older HIV-positive adults on suppressive antiretroviral therapy. AIDS 31:787-795
Montoya, Jessica L; Iudicello, Jennifer; Fazeli, Pariya L et al. (2017) Elevated Markers of Vascular Remodeling and Arterial Stiffness Are Associated With Neurocognitive Function in Older HIV+ Adults on Suppressive Antiretroviral Therapy. J Acquir Immune Defic Syndr 74:134-141
Fazeli, Pariya L; Moore, David J; Franklin, Donald R et al. (2016) Lower CSF A? is Associated with HAND in HIV-Infected Adults with a Family History of Dementia. Curr HIV Res 14:324-30
Bryant, Alex K; Fazeli, Pariya L; Letendre, Scott L et al. (2016) Complement Component 3 Is Associated with Metabolic Comorbidities in Older HIV-Positive Adults. AIDS Res Hum Retroviruses 32:271-8

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