The aim of this Program's revised renewal application is to clarify the mechanisms of methamphetamine (METH) potentiation of HIV neural injury. Given the prevalence of co-infection with hepatitis C (HCV), as well as the growing awareness of HCV as a co-factor in neural injury, the Program will examine the separate and combined effects of HIV, METH and HCV. Scientific hypotheses for the Program are based on an overall model proposing that HIV, METH and HCV can act both directly and indirectly through immune cell activation that alters the balance between neuroprotective and neurotoxic mediators, leading to injury of specific neuronal subpopulations in the neocortex and nigrostriatum. The Program utilizes a multifaceted and translational approach through six Projects (Neurocognitive, Neuromotor, fMRI, Carbon 13 Spectroscopy, Biomarkers, Neurobiology). Innovative directions include deployment of neurocognitive, neuromotor, and neuroimaging methods hypothesized to be more sensitive and specific in detecting underlying mechanisms of injury from HIV, METH, and HCV and linking these to in vivo and in vitro molecular studies. Programmatic scientific leadership, synergy, coordination, basic evaluating, and effective use of shared resources are provided by a Core served by the Executive, Participant Accrual and Retention, Data Management and Information Systems, Statistics, and Clinical Assessment Units. Through coordinated multidisciplinary research addressing the neurotoxic effects of HIV, METH and HCV at different levels of analysis we hope to achieve a more precise understanding of the nature and mechanisms of neural injury attributable to these factors. Understanding these mechanisms will provide a basis for the future development of targeted treatment interventions. The application has been strengthened by attending to reviewer concerns regarding participant recruitment and approach to confounds; by providing new preliminary data in the revised projects to support their feasibility and refine their hypotheses; and clarifying each Project's role in the Program's overall aims, as well as their synergy and interaction among themselves.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program Projects (P01)
Project #
5P01DA012065-08
Application #
7215268
Study Section
Special Emphasis Panel (ZDA1-PXC-V (17))
Program Officer
Lin, Yu
Project Start
2000-07-01
Project End
2010-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
8
Fiscal Year
2007
Total Cost
$2,173,996
Indirect Cost
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
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
Dufour, Catherine A; Marquine, María J; Fazeli, Pariya L et al. (2018) A Longitudinal Analysis of the Impact of Physical Activity on Neurocognitive Functioning Among HIV-Infected Adults. AIDS Behav 22:1562-1572
Oppenheim, Hannah; Paolillo, Emily W; Moore, Raeanne C et al. (2018) Neurocognitive functioning predicts frailty index in HIV. Neurology 91:e162-e170
Paolillo, Emily W; Gongvatana, Assawin; Umlauf, Anya et al. (2017) At-Risk Alcohol Use is Associated with Antiretroviral Treatment Nonadherence Among Adults Living with HIV/AIDS. Alcohol Clin Exp Res 41:1518-1525
Marquine, María J; Montoya, Jessica L; Umlauf, Anya et al. (2016) The Veterans Aging Cohort Study (VACS) Index and Neurocognitive Change: A Longitudinal Study. Clin Infect Dis 63:694-702
Soontornniyomkij, Virawudh; Kesby, James P; Morgan, Erin E et al. (2016) Effects of HIV and Methamphetamine on Brain and Behavior: Evidence from Human Studies and Animal Models. J Neuroimmune Pharmacol 11:495-510
Bharti, Ajay R; McCutchan, Allen; Deutsch, Reena et al. (2016) Latent Toxoplasma Infection and Higher Toxoplasma gondii Immunoglobulin G Levels Are Associated With Worse Neurocognitive Functioning in HIV-Infected Adults. Clin Infect Dis 63:1655-1660
Bharti, Ajay R; Woods, Steven Paul; Ellis, Ronald J et al. (2016) Fibroblast growth factors 1 and 2 in cerebrospinal fluid are associated with HIV disease, methamphetamine use, and neurocognitive functioning. HIV AIDS (Auckl) 8:93-9
Marquine, M J; Sakamoto, M; Dufour, C et al. (2016) The impact of ethnicity/race on the association between the Veterans Aging Cohort Study (VACS) Index and neurocognitive function among HIV-infected persons. J Neurovirol 22:442-54
Ma, Qing; Vaida, Florin; Wong, Jenna et al. (2016) Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients. J Neurovirol 22:170-8

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