This is a revised application for Project by Letendre. This Project will use a translational approach to understand the effects of METH, HIV, and HCV on the brain by using in vivo biomarkers as windows into cellular and molecular mechanisms of neuropathogenesis. We will examine six categories of biomarkers (astroglial, inflammatory, oxidative, trophic, neuronal, and viral), which correspond to the major pathogenic mechanisms outlined in our conceptual model.
The specific aims will be to identify distinct biomarker profiles that are associated with METH, HIV, and HCV; to identify the relationships between METH and HIV and two specific groups of biomarkers, fibroblast growth factors (FGFs) and interferon-inducible proteins; and to determine the relationships between biomarker profiles and key indicators of brain injury being studied in other Projects, including neurocognitive impairment, movement disorders, altered regional brain activation, and changes in glutamine-glutamate cycling. To accomplish these aims, we will examine biomarker concentrations in CSF from 425 participants from the three risk groups enrolled into this Program. We will also examine changes in biomarker profiles and CSF concentrations of interferon (IFN)-alpha in response to PEG-IFN-alpha/ribavirin treatment of HCV infection in METH+ individuals enrolled in Study 2 of Project by Heaton. In order to more specifically determine the effects of recent versus long-term abstinence from METH on biomarker profiles, an added group of 50 METH users who have used within 10 days will be enrolled specifically for this Project. These experiments are innovative because they will determine the unique biomarker signatures of METH, HIV, and HCV; measure CSF markers reflecting multiple mechanisms of injury in the same specimens; investigate recently recognized mechanisms of injury, such as FGFs; link in vivo and in vitro findings; and determine the effects of PEG-IFN-alpha and ribavirin on putative in vivo markers of neuropathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Program Projects (P01)
Project #
2P01DA012065-06A1
Application #
6947424
Study Section
Special Emphasis Panel (ZDA1-PXC-V (17))
Project Start
2005-04-01
Project End
2010-03-31
Budget Start
2005-04-01
Budget End
2006-04-30
Support Year
6
Fiscal Year
2005
Total Cost
$150,118
Indirect Cost
Name
University of California San Diego
Department
Type
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

Showing the most recent 10 out of 132 publications