Methamphetamine and HIV Infection

描述(由申请人提供)：甲基苯丙胺(冰毒)的使用在人类免疫缺陷病毒(HIV)感染的患者中很常见，并有可能抑制对HIV感染的免疫反应。这项研究的总体目的是确定冰毒对艾滋病毒感染和病毒特异性免疫反应的直接影响。我们将在拟议的研究中使用一个独特的受试者群体，中国冰毒使用者，因为中国中的大多数冰毒使用者都是简单的使用者。我们假设冰毒的使用损害了特定的免疫功能，促进了艾滋病毒的复制。为了解决这一重要假说，我们将首先检验冰毒使用是否会增加从吸食艾滋病毒和正常受试者中分离出来的巨噬细胞和CD4+T细胞的HIV感染。然后，我们将确定体内冰毒暴露是否会影响HIV载量和CD4+/CD8+T淋巴细胞计数。我们还将确定体内使用冰毒对CD4+T细胞和单核细胞上HIV辅助受体(CCR5和CXCR4)表达以及血浆CC趋化因子(MIP-1、2和RANTES)水平的影响。这些互补的特定目标将为冰毒对人类免疫系统和艾滋病毒感染的病理影响提供见解。拟议的研究如果成功，将有助于更好地了解冰毒是否以及如何影响个人对艾滋病毒感染的易感性，并促进病毒复制。我们的研究也将有助于为减少吸毒人群中使用冰毒的实际指导提供合理的基础。 项目简介：该项目建议进行体外和体内研究，使用一个独特的受试者群体--中国冰毒使用者，直接研究甲基苯丙胺在上调艾滋病毒感染和特异性免疫功能受损中的作用。拟议中的研究如果成功，将提供直接证据，证明冰毒在损害宿主免疫系统和促进艾滋病毒复制方面具有辅助因素作用。

DESCRIPTION (provided by applicant): Methamphetamine (METH) use is common among human immunodeficiency virus (HIV) infected patients and has the potential to suppress immune response to HIV infection. The general aim of this study is to determine the direct impact of METH on HIV infection and viral- specific immune response. We will use a unique subject population, Chinese METH users, for the proposed study, as most METH users in China are simple users. We hypothesize that METH use impairs specific immune function and promotes HIV replication. In order to address this important hypothesis, we will first examine whether METH use increases HIV infection of macrophages and CD4+ T cells isolated from HIV- METH-using and normal subjects. We will then determine whether in vivo METH exposure affects HIV loads and CD4+/CD8+ T lymphocytes counts. We will also determine the in vivo impact of METH use on the expression of HIV coreceptors (CCR5 and CXCR4) on CD4+ T cells and monocytes and plasma levels of CC-chemokines (MIP-1, 2, and RANTES). These complementary specific aims will provide insights into METH-mediated pathological impact on human immune system and HIV infection. The proposed studies, if successful, will contribute to a better understanding about whether and how METH affects the susceptibility of an individual to HIV infection and promotes viral replication. Our studies also will facilitate a rational basis for practical guidance towards the reduction of the usage of METH among drug abusing population. Project Narrative: This project proposes both ex vivo and in vivo studies using a unique subject population, Chinese METH users, to directly address the role of methamphetamine (METH) in upregulation of HIV infection and impairment of specific immune function. The proposed studies, if successful, will provide direct evidence that METH has a cofactor role in impairing host immune system and promoting HIV replication.