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.

National Institute of Health (NIH)
Research Project (R01)
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Behavioral and Social Consequences of HIV/AIDS Study Section (BSCH)
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Stoff, David M
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University of California San Diego
Schools of Medicine
La Jolla
United States
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