The primary goal of this project is to determine the effect of chronic heavy alcohol use on event-related potential and EEG coherence measures on functional CNS morbidity of HIV disease. Chronic heavy alcohol use may affect HIV CNS effects on treatment seeking and treatment adherence) or result in a reduced treatment response which would cause increased CNS morbidity. It can also have direct and specific effects on the CNS independent of the progression of the overall HIV disease process. Both of these mechanisms and their effect will be evaluated in a cross-sectional study of HIV+ and HIV- chronic heavy drinkers and light/non-drinkers with longitudinal follow-up at two years. Our synergistic model of HIV infection and alcohol use predicts that the CNS morbidity in individuals who are HIV+ and are chronic heavy alcohol users will be greater than the sum of that in individuals who are HIV+ light/non-drinkers and that in individuals who are HIV-chronic heavy drinkers. We hypothesize that this synergy will occur as a result of behavioral effects of heavy alcohol use on treatment seeking, treatment adherence, nutrition, or risk behaviors (which could lead to repeated inoculations with new viral strains) or biological effects of heavy alcohol user (e.g., possible effects on the metabolism and bioavailability of treatment medications). We will: (1) determine whether chronic heavy alcohol using HIV+ individuals have greater CNS morbidity as measured by electrophysiological testing than do light/non-drinking HIV+ individuals, 92) determine whether HIV+ heavy drinking individuals' CNS morbidity as measured by electrophysiological testing has a greater rate of progression or a lesser treatment response compared to HIV+ light/non-drinking individuals, (3) determine whether the effects of chronic heavy alcohol use and HIV infection on electrophysiological measurements of CNS morbidity at baseline and over the follow-up period are additive or, exceeding additive effects, (4) within the context of the Program Project Grant, test hypotheses both about the mechanisms underlying CNS information processing disabilities and about the impact of these disabilities of clinically important outcomes. We will recruit and study four groups of subjects: 120 chronic heavy alcohol drinking HIV+ individuals, 120 light/non-drinking HIV+ individuals, 60 chronic heavy drinking HIV-individuals, and 60 light/non- drinking HIV-individuals. We will examine the integrity and speed of various information processing operations involving cortico-cortical and subcortical-cortical connections and/or cortical/subcortical regions. Information processing abilities will be assess by electroencephalographic (EEG) measures of cortical connectivity and event-related potential (ERP) indices of the activation of semantic networks and of the brain's orienting response to novel stimuli.
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