Although the prevalence of frank dementia has decreased in the era of combination antiretroviral therapies (cART), HIV-associated neurocognitive disorders (HAND) remain common and continue to negatively impact health outcomes. Older HIV-infected adults (O+) represent a growing subpopulation of the U.S. epidemic that is especially vulnerable to HAND and its adverse impact on cART adherence and HIV-related disability. Yet there are presently no neuropsychological treatments validated for management of HAND and its functional consequences (e.g., non-adherence) in O+. Prospective memory (PM) is a viable construct upon which to develop novel cognitive neurorehabilitation strategies to improve health outcomes in HAND among O+. PM is a unique and ubiquitous aspect of cognition that encompasses the complex process of """"""""remembering to remember"""""""". Over the prior grant periods we have shown that O+ are at particular risk of deficits in the strategic aspects of PM, which are strongly and independently predictive of HIV-related disability, including unemployment and cART non-adherence. Building on this foundation, our revised renewal application endeavors to translate the observational knowledge gained about PM in HIV from the prior funding period into an effective, theory-driven, PM-based intervention for HAND among O+. Specifically, this renewal will determine whether enhancing the strategic aspects of PM as guided by the influential Multiprocess Theory (McDaniel &Einstein, 2000) improves PM in the laboratory and in daily life (i.e., a naturalistic task).
Study aims will be evaluated in 200 O+ and 50 demographically comparable seronegative participants (O-), who will receive a comprehensive medical, psychiatric, and neurocognitive assessment at the UCSD HIV Neurobehavioral Research Program (HNRP). All participants will undergo a series of parallel laboratory and naturalistic experiments designed to test the hypothesis that bolstering strategic processing will significantly improve (and """"""""normalize"""""""") PM performance among O+. This revised application responds to the initial review by providing feasibility data for the naturalistic PM experiments, adding measures of daily intervening events and memory strategies, and clarifying several theoretical and logistical issues. The translational nature of tis study will also allow us to determine whether the magnitude of the PM benefits gained through supporting strategic processing among O+ in the laboratory are associated with a parallel response in the naturalistic setting in the same individuals. Findings from these treatment-focused experimental investigations are expected to serve as a springboard for a subsequent Phase I clinical trial. Accordingly, this renewal application represents a critical translational sep in converting observational cohort-based findings into novel treatments for HAND that may improve health outcomes among O+.

Public Health Relevance

HIV-associated neurocognitive disorders (HAND) are highly prevalent and negatively impact everyday functioning, yet there are no validated neurocognitive therapies aimed at improving cognition in HIV. Prospective memory (PM), which is a unique cognitive construct describing the ability of remembering to remember, is impaired in HIV, plays a vital role in everyday activities (e.g., adhering to medications), and as such, may be a viable target for neurocognitive interventions. Thus, this program of research takes a theoretically-driven approach towards improving HIV-associated PM deficits in the laboratory and naturalistic settings in order to inform the development of novel, effective neurorehabilitatio strategies for improving HAND and enhancing overall quality of life.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH073419-10
Application #
8743267
Study Section
Behavioral and Social Consequences of HIV/AIDS Study Section (BSCH)
Program Officer
Stoff, David M
Project Start
2004-12-01
Project End
2018-06-30
Budget Start
2014-07-01
Budget End
2015-06-30
Support Year
10
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Kordovski, Victoria M; Woods, Steven Paul; Verduzco, Marizela et al. (2017) The effects of aging and HIV disease on employment status and functioning. Rehabil Psychol 62:591-599
Oliveira, Michelli F; Chaillon, Antoine; Nakazawa, Masato et al. (2017) Early Antiretroviral Therapy Is Associated with Lower HIV DNA Molecular Diversity and Lower Inflammation in Cerebrospinal Fluid but Does Not Prevent the Establishment of Compartmentalized HIV DNA Populations. PLoS Pathog 13:e1006112
Faytell, Marika P; Doyle, Katie L; Naar-King, Sylvie et al. (2017) Visualisation of future task performance improves naturalistic prospective memory for some younger adults living with HIV disease. Neuropsychol Rehabil 27:1142-1155
Sheppard, David P; Iudicello, Jennifer E; Morgan, Erin E et al. (2017) Accelerated and accentuated neurocognitive aging in HIV infection. J Neurovirol 23:492-500
Woods, Steven Paul; Iudicello, Jennifer E; Morgan, Erin E et al. (2017) Household Everyday Functioning in the Internet Age: Online Shopping and Banking Skills Are Affected in HIV-Associated Neurocognitive Disorders. J Int Neuropsychol Soc 23:605-615
Pérez-Santiago, Josué; De Oliveira, Michelli F; Var, Susanna R et al. (2017) Increased cell-free mitochondrial DNA is a marker of ongoing inflammation and better neurocognitive function in virologically suppressed HIV-infected individuals. J Neurovirol 23:283-289
Doyle, Katie L; Woods, Steven Paul; McDonald, Carrie R et al. (2017) Verbal episodic memory profiles in HIV-Associated Neurocognitive Disorders (HAND): A comparison with Huntington's disease and mesial temporal lobe epilepsy. Appl Neuropsychol Adult :1-11
Avci, Gunes; Woods, Steven P; Verduzco, Marizela et al. (2017) Effect of Retrieval Practice on Short-Term and Long-Term Retention in HIV+ Individuals. J Int Neuropsychol Soc 23:214-222
Tierney, Savanna M; Sheppard, David P; Kordovski, Victoria M et al. (2017) A comparison of the sensitivity, stability, and reliability of three diagnostic schemes for HIV-associated neurocognitive disorders. J Neurovirol 23:404-421
Kordovski, Victoria M; Woods, Steven Paul; Avci, Gunes et al. (2017) Is the Newest Vital Sign a Useful Measure of Health Literacy in HIV Disease? J Int Assoc Provid AIDS Care 16:595-602

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