HIV and methamphetamine (METH) are each associated with deleterious effects on the central nervous system (CNS). Although early evidence suggests that HIV and METH may interact to amplify neural injury via common pathways involving neuroinflammation and vasculopathy, their combined effects on the CNS remain poorly understood. To foster this line of research we propose establishing the Translational Methamphetamine AIDS Research Center (TMARC), which aims to provide scientific leadership, technical support, and opportunities for training to coalesce the efforts of an interdisciplinary group of investigators to elucidate METH/HIV-induced CNS injury. Human projects will examine inhibitory deficits (PI), dysregulated reward processing, interoception, and risk taking (P2), and the effect of HIV co-receptor tropism change on neurocognitive impairment and disease progression (P3). Animal studies will complement and extend the human studies: P4 will explore cognitive and reward effects of METH in a gp120 mouse model, while P5 will explore METH effects on a CCR5 knockout gp120 mouse model with electrophysiological, neuropathological, and neurochemical methods. A third animal project will be nested within PI to enhance translation of the human studies on inhibition to animals. Supporting these Projects will be 4 scientific Cores (Clinical Assessment and Laboratory;Neuropsychiatric;Neuroimaging;Neuroscience and Animal Models) whose activities will be synergized by an Administrative Coordinating Core that includes Units on Data Management and Information Systems, Statistics, and Participant accrual and tracking. These Cores will also serve as incubators for innovative pilot work to facilitate initiation of new studies, and will also serve as a resource by providing access to cohorts, biological samples, and data to inform future studies both by TMARC-affiliated and external investigators. TMARC will also provide opportunities for trainees to develop new research ideas on the CNS effects of HIV and drugs, thereby fostering the next generation of scientists. TMARC's ultimate vision is to become a national resource for translational multidisciplinary research and training in the neuropathogenesis of HIV and substance use.

Public Health Relevance

Powerful antiviral treatments for HIV have reduced mortality, yet neurological complications remain prevalent, perhaps due to drugs of abuse such as METH amplifying HIV's effects. TMARC will provide scientific leadership, technical support, and training for translational research on the combined CNS effects of HIV infection &METH use, which are highly interconnected conditions of major public health importance.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA026306-05
Application #
8472465
Study Section
Special Emphasis Panel (ZDA1-EXL-T (11))
Program Officer
Lin, Yu
Project Start
2009-09-30
Project End
2014-05-31
Budget Start
2013-06-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2013
Total Cost
$3,175,712
Indirect Cost
$1,059,081
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
Walker, Keenan A; Brown, Gregory G (2018) HIV-associated executive dysfunction in the era of modern antiretroviral therapy: A systematic review and meta-analysis. J Clin Exp Neuropsychol 40:357-376
Stecher, Melanie; Hoenigl, Martin; Eis-Hübinger, Anna Maria et al. (2018) Hotspots of Transmission Driving the Local Hiv Epidemic in the Cologne-Bonn Region, Germany. Clin Infect Dis :
Paolillo, Emily W; Obermeit, Lisa C; Tang, Bin et al. (2018) Smartphone-based ecological momentary assessment (EMA) of alcohol and cannabis use in older adults with and without HIV infection. Addict Behav 83:102-108
Thaney, Victoria E; Kaul, Marcus (2018) Type I Interferons in NeuroHIV. Viral Immunol :
Soontornniyomkij, Virawudh; Umlauf, Anya; Soontornniyomkij, Benchawanna et al. (2018) Association of antiretroviral therapy with brain aging changes among HIV-infected adults. AIDS 32:2005-2015
Thaney, Victoria E; Sanchez, Ana B; Fields, Jerel A et al. (2018) Transgenic mice expressing HIV-1 envelope protein gp120 in the brain as an animal model in neuroAIDS research. J Neurovirol 24:156-167
Kesby, James P; Chang, Ariel; Markou, Athina et al. (2018) Modeling human methamphetamine use patterns in mice: chronic and binge methamphetamine exposure, reward function and neurochemistry. Addict Biol 23:206-218
Hoenigl, Martin; Jain, Sonia; Moore, David et al. (2018) Substance Use and Adherence to HIV Preexposure Prophylaxis for Men Who Have Sex with Men1. Emerg Infect Dis 24:
Moore, David J; Pasipanodya, Elizabeth C; Umlauf, Anya et al. (2018) Individualized texting for adherence building (iTAB) for methamphetamine users living with HIV: A pilot randomized clinical trial. Drug Alcohol Depend 189:154-160
MacDuffie, Katherine E; Brown, Gregory G; McKenna, Benjamin S et al. (2018) Effects of HIV Infection, methamphetamine dependence and age on cortical thickness, area and volume. Neuroimage Clin 20:1044-1052

Showing the most recent 10 out of 148 publications