Methamphetamine and AIDS in a Non-Human Primate Model

描述(由申请人提供)：俱乐部毒品被年轻人广泛使用，在同性恋社区中更受欢迎(男男性行为者；男男性接触者)。现已确定，甲基苯丙胺使用者中艾滋病毒血清阳性率较高，已知甲基苯丙胺会导致艾滋病毒阳性个人中的艾滋病毒相关性痴呆(HAD)。也有间接和暗示的迹象表明，甲基苯丙胺影响病毒复制、流行和疾病进展。测试关于甲基苯丙胺在艾滋病毒阳性人群中的作用的概念验证研究的前景是站不住脚的，因为解决这一重要问题需要不同的潜伏期和很长的时间。因此，在HIV/AIDS猕猴模型中进行精心设计的研究是非常有必要的，这将有助于在相对较短的时间内总结甲基苯丙胺滥用对慢病毒发病、神经功能障碍和疾病进展的影响。我们建议在此应用程序中解决这些问题。本申请建议(I)建立慢性甲基苯丙胺暴露的SIV-SIV/猕猴模型，并研究甲基苯丙胺滥用是否加速了猕猴艾滋病的发病，(Ii)确定慢性甲基苯丙胺暴露是否影响艾滋病SIV-SIV/猕猴模型中的病毒特异性细胞、体液和粘膜免疫反应，(Iii)确定甲基苯丙胺和SIV/SIV相互作用是否导致脑内病毒/宿主相互作用的神经病理效应增强以及多巴胺能系统的改变，以及(Iv)确定与对照动物相比，甲基苯丙胺暴露的猕猴的病毒进化是否不同。

DESCRIPTION (provided by applicant): Club drugs are extensively used by young people with more popularity among gay community (men having sex with men; MSM). It has been established that HIV seroprevalence is higher among methamphetamine users and methamphetamine is known to contribute to HIV-associated dementia (HAD) among HIV-positive individuals. There are also indirect and suggestive indications available that methamphetamine affects the virus replication, prevalence and progression of disease. The prospect of testing proof-of-concept studies regarding the role of methamphetamine in HIV positive humans is untenable because of the variable incubation periods and long time required to address this important issue. Therefore a well-designed study in the macaque model of HIV/AIDS is greatly warranted that will help conclude the effect of methamphetamine abuse on lentivirus pathogenesis, neurological disorder and disease progression in relatively short time. We propose to address these issues in this application. The application proposes to (i) establish the SIV-SHIV/macaque model of chronic methamphetamine exposure and examine whether methamphetamine abuse accelerates the onset of AIDS in macaques, (ii) determine whether chronic methamphetamine exposure affects virus-specific cellular, humoral and mucosal immune responses in SIV- SHIV/macaque model of AIDS, (iii) determine whether METH and SHIV/SIV interaction causes enhanced neuropathological effects on the virus/host interaction in the brain and alterations in dopaminergic systems, and (iv) determine whether virus evolution is different in methamphetamine-exposed macaques compared to that in the control animals.