As many as 40% of AIDS patients have been reported to suffer from alcoholism; however, little is known about the effect of alcohol abuse on AIDS. This proposal will develop a nonhuman primate (NHP) model of alcohol abuse and AIDS and will provide an important tool to help understand alcohol's effects on the progression of AIDS. The proposed research will develop a NHP model for the experimental analysis of both chronic, long-term alcohol consumption and HIV/AIDS. The model to be explored will combine current oral ethanol self-dosing techniques with a well-defined simian immunodeficiency virus (SIV)-macaque model of HIV/AIDS to investigate the viral, behavioral, and CNS consequences associated with chronic high-dose oral ethanol consumption, SIV viruses, and their combination. Automated oral self-dosing techniques will be employed to establish chronic high-dose oral ethanol consumption in macaques. Core body temperature and general activity, measures known to be sensitive to the effects of ethanol, will be continuously monitored by telemetry. Behavioral observations will monitor possible development of physical dependence and/or withdrawal. Assays of immune system function will be performed periodically throughout the experiment. Using these techniques, temperature, general activity, and behavioral observations and measures of immune system function will be recorded during baseline conditions, the development and maintenance of chronic ethanol ingestion, and during short-term abstinence. The effects of chronic high-dose oral ethanol consumption on the progression of SIV disease will be assessed by comparing all measures (body temperature, general activity, immune system function) in groups of ethanol-consuming and ethanol-free animals throughout SIV disease. Post mortem analysis will compare the severity of CNS pathology between ethanol-exposed and ethanol-naive animals. The proposed studies will provide important information on how ethanol consumption affects the course of SIV infection and the progression to AIDS. Furthermore, the proposed studies will investigate whether chronic alcohol consumption increases the CNS pathology produced by SlV infection. Once developed this model could be readily expanded to study alcohol's effects on a number of systems, including immune system function, cognitive and behavioral processes, and more detailed analysis of alcohol's effects on HIV/AIDS. By changing the availability of ethanol, the model could also investigate the effects of different patterns of alcohol exposure, including abstinence after chronic alcohol consumption and/or patterns of 'binge' drinking.
