Alcohol Use and AIDS: An SIV/Macaque Model

描述（申请人提供）：据报道，多达40%的艾滋病患者患有酒精中毒；然而，人们对酗酒对艾滋病的影响知之甚少。这一建议将建立一个酒精滥用和艾滋病的非人类灵长类动物模型，并将提供一个重要的工具来帮助了解酒精对艾滋病进展的影响。拟议的研究将开发一个NHP模型，用于慢性、长期饮酒和艾滋病毒/艾滋病的实验分析。该模型将结合当前口服乙醇自给药技术和定义明确的猴免疫缺陷病毒(SIV)-猕猴HIV/AIDS模型，研究慢性大剂量口服乙醇、SIV病毒及其组合对病毒、行为和中枢神经系统的影响。自动口服自给药技术将用于建立猕猴慢性大剂量口服乙醇消耗量。核心体温和一般活动，这些已知对乙醇的影响很敏感的指标，将通过遥测技术持续监测。行为观察将监测身体依赖和/或戒断的可能发展。免疫系统功能检测将在整个实验过程中定期进行。使用这些技术，在基线条件下，慢性乙醇摄入的发展和维持以及短期戒酒期间，将记录温度、一般活动、行为观察和免疫系统功能的测量。长期大剂量口服乙醇对SIV疾病进展的影响将通过比较摄入乙醇组和不摄入乙醇组在SIV疾病期间的所有测量（体温、一般活动、免疫系统功能）来评估。死后分析将比较乙醇暴露和未接触乙醇的动物中枢神经系统病理的严重程度。拟议的研究将为乙醇消费如何影响SIV感染的过程和艾滋病的进展提供重要信息。此外，拟议的研究将调查慢性饮酒是否会增加SlV感染引起的中枢神经系统病理。一旦发展起来，这个模型可以很容易地扩展到研究酒精对许多系统的影响，包括免疫系统功能、认知和行为过程，以及更详细地分析酒精对艾滋病毒/艾滋病的影响。通过改变乙醇的可用性，该模型还可以研究不同酒精暴露模式的影响，包括长期饮酒后的戒酒和/或“狂欢”饮酒模式。

DESCRIPTION (provided by applicant): 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.