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，人们对酒精滥用对艾滋病的影响知之甚少。这项提议将开发一个酒精滥用和艾滋病的非人类灵长类动物(NHP)模型，并将提供一个重要工具，帮助了解酒精对艾滋病进展的影响。这项拟议的研究将开发一个NHP模型，用于长期饮酒和艾滋病毒/艾滋病的实验分析。将要探索的模型将结合目前的口服乙醇自我给药技术和定义明确的艾滋病毒/艾滋病猴免疫缺陷病毒(SIV)-猕猴模型，以调查与慢性高剂量口服酒精摄入、SIV病毒及其组合相关的病毒、行为和中枢神经系统的后果。自动口服自我给药技术将被用于建立猕猴长期高剂量口服乙醇消费。核心体温和一般活动，即已知对乙醇影响敏感的指标，将通过遥测进行持续监测。行为观察将监测身体依赖和/或戒断的可能发展。在整个实验过程中，将定期进行免疫系统功能的分析。使用这些技术，将在基线条件、慢性酒精摄入的发展和维持以及短期戒酒期间记录体温、一般活动和免疫系统功能的行为观察和测量。长期高剂量口服酒精摄入对SIV疾病进展的影响将通过比较整个SIV疾病期间酒精消耗组和非酒精组的所有指标(体温、一般活动、免疫系统功能)来评估。尸检分析将比较酒精暴露和未接触酒精的动物中枢神经系统病理的严重程度。拟议的研究将提供有关酒精消费如何影响SIV感染过程和发展为艾滋病的重要信息。此外，拟议的研究将调查长期饮酒是否会增加SLV感染所产生的中枢神经系统病理。一旦开发出来，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。通过改变乙醇的可获得性，该模型还可以研究不同酒精暴露模式的影响，包括长期饮酒后的禁欲和/或酗酒模式。

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.