As people are now aging with HIV-infection, there is evidence that the cumulative incidence of HAND is continuing to increase 8-12. It is not currently understood why some HIV-infected individuals develop cognitive impairments while others do not. Likewise, there are no biological measures that can identify individuals with asymptomatic neurocognitive impairments (ANI) who are likely to progress to more severe forms of cognitive impairments including mild neurocognitive disorder (MND) or frank dementia (HIV associated dementia;HAD), or who is likely to spontaneously improve. The objective of this proposal is to use combinational informatics approaches to identify neural systems that are perturbed early in the course of HAND, and to determine how longitudinal changes in neural systems are related to changes in cognitive function. These combined informatics approaches will break new ground in the molecular understanding of HAND that will aid in the development new classes of neuroprotective drugs. These approaches are also likely to pinpoint a unique set of surrogate markers that may identify HIV infected individuals at a prodromal phase of HAND, when neuroprotective therapeutic intervention would have the greatest benefit. To accomplish these goals we propose to use a combinational informatics systems approach to interrogate a unique set of clinical samples that have undergone extensive analysis at multiple performance sites.

Public Health Relevance

Although combined antiretroviral therapies are able to suppress HIV replication, the cumulative prevalence of HIV-Associated Neurocognitive Disorders (HAND) has not decreased, and may be increasing. New therapies are required to protect the CNS in HIV-infected individuals. In this application we propose to better understand the molecular mechanisms that underlie the development of cognitive impairment in HIV infected individuals so that we can identify those at risk for developing cognitive impairments, and develop therapies that target neural systems perturbed in HIV infection.

Agency
National Institute of Health (NIH)
Type
Small Research Grants (R03)
Project #
1R03MH103985-01
Application #
8722779
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Brouwers, Pim
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Neurology
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Bae, Mihyun; Bandaru, Veera Venkata Ratnam; Patel, Neha et al. (2014) Ceramide metabolism analysis in a model of binge drinking reveals both neuroprotective and toxic effects of ethanol. J Neurochem 131:645-54