There is a high incidence of chronic heavy alcohol use, which has known CNS toxicity, in populations at high risk for HIV infection. The main goal of this project is to determine the degree to which chronic alcohol use increases the CNS morbidity of HIV infection via a) direct effects, b) hastening the progression of the overall HIV disease process, or c) reducing treatment response. Our synergistic model of HIV infection and alcohol use predicts that the CNS morbidity in individuals who are HIV+ and chronic heavy alcohol users will be greater than the sum of that due to HIV infection or chronic alcohol use alone. Our goal will be achieved by using in vivo multi-slice proton magnetic resonance spectroscopic imaging (1 H MRSI) to measure the spatial and temporal patterns of brain neuron viability ( measured by N-acetylaspartate, a putative neuron maker) and gliosis (measured by choline-containing metabolites). We will measure brain region-specific /1H metabolite concentrations in four subject groups: 1) 120 HIV+ heavy chronic alcohol users, 2) 120 HIV+ light/non-drinkers, 3) 60 HIV-heavy chronic alcohol users, and 4) 60 HIV- light/non-drinkers. The two HIV+ samples will be matched for degree of systemic immunosuppression by CD4 percent, the two drinking samples will be matched on alcohol consumption.
The specific aims of this cross-section and longitudinal study are to (1) determine whether chronic heavy alcohol using HIV-infected individuals have greater CNS morbidity than light/non- drinking HIV-infected individuals, (2) determine whether chronic heavy alcohol using HIV-infected individuals have a greater rate of progression of CNS morbidity and/or a lesser treatment response than light/non- drinking HIV-infected individuals have a greater rate of progression of CNS morbidity and/or a lesser treatment response than light/non-drinking HIV-infected individuals, (3) determine whether the effects of chronic heavy alcohol use and HIV infection on CNS morbidity and progression are additive or, as predicted by our synergistic model, exceed additive effects, and (4) test hypothesis both about the mechanisms underlying CNS metabolic abnormalities and about their impact on clinically important outcomes. Measurements of /1H metabolite concentrations are expected to facilitate early detection of brain involvement in HIV disease and alcohol abuse, possibly before structural brain changes and/or any definitive impairments are clinically evident, and they may predict the later development of structural changes and clinically significant impairments. This /1H MRSI could prove important in instituting aggressive interventions early in HIV CNS disease progression. By documenting neuronal and gliotic effects of chronic heavy alcohol use among HIV+ individuals, this project will help establish the magnitude of the public health problems posed by such use. It will also provide important information on whether and how chronic heavy alcohol use compromises the efficacy of anti-retroviral therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Program Projects (P01)
Project #
5P01AA011493-04
Application #
6495555
Study Section
Project Start
2001-09-01
Project End
2002-08-31
Budget Start
Budget End
Support Year
4
Fiscal Year
2001
Total Cost
Indirect Cost
Name
Northern California Institute Research & Education
Department
Type
DUNS #
City
San Francisco
State
CA
Country
United States
Zip Code
94121
Cardenas, Valerie A; Durazzo, Timothy C; Gazdzinski, Stefan et al. (2011) Brain morphology at entry into treatment for alcohol dependence is related to relapse propensity. Biol Psychiatry 70:561-7
Van Boven, Robert W; Harrington, Greg S; Hackney, David B et al. (2009) Advances in neuroimaging of traumatic brain injury and posttraumatic stress disorder. J Rehabil Res Dev 46:717-57
Pa, Judy; Boxer, Adam; Chao, Linda L et al. (2009) Clinical-neuroimaging characteristics of dysexecutive mild cognitive impairment. Ann Neurol 65:414-23
Cardenas, V A; Meyerhoff, D J; Studholme, C et al. (2009) Evidence for ongoing brain injury in human immunodeficiency virus-positive patients treated with antiretroviral therapy. J Neurovirol 15:324-33
Studholme, Colin (2008) Dense feature deformation morphometry: Incorporating DTI data into conventional MRI morphometry. Med Image Anal 12:742-51
Gazdzinski, Stefan; Durazzo, Timothy C; Weiner, Michael W et al. (2008) Are treated alcoholics representative of the entire population with alcohol use disorders? A magnetic resonance study of brain injury. Alcohol 42:67-76
Gazdzinski, Stefan; Kornak, John; Weiner, Michael W et al. (2008) Body mass index and magnetic resonance markers of brain integrity in adults. Ann Neurol 63:652-7
Durazzo, Timothy C; Cardenas, Valerie A; Studholme, Colin et al. (2007) Non-treatment-seeking heavy drinkers: effects of chronic cigarette smoking on brain structure. Drug Alcohol Depend 87:76-82
Durazzo, Timothy C; Gazdzinski, Stefan; Meyerhoff, Dieter J (2007) The neurobiological and neurocognitive consequences of chronic cigarette smoking in alcohol use disorders. Alcohol Alcohol 42:174-85
Studholme, Colin (2007) Incorporating DTI data as a constraint in deformation tensor morphometry between T1 MR images. Inf Process Med Imaging 20:223-32

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