Neurobehavioral Effects of HIV & Host Genetics in China

描述（由申请人提供）：西方国家的研究表明，神经心理（NP）损伤是HIV感染的常见后果，与日常功能下降和医疗预后不良（早期死亡）有关。中国（13亿人口）的艾滋病疫情呈指数级增长。虽然宿主遗传学、治疗和辅因子（例如，其他感染）可能导致不同的神经行为结果，在中国还没有关于神经艾滋病的研究。中国政府高度重视艾滋病防治工作。在美国国家卫生研究院的支持下，中国疾病预防控制中心启动了中国艾滋病综合国际研究计划（CIPRA），并开始对中国两个主要的艾滋病风险人群进行一系列研究：注射吸毒者（IDUs）和前血浆捐献者（FPD）。 在此，我们提出了在中国的第一个研究艾滋病相关的神经行为障碍。我们将与中国疾病预防控制中心的同事合作，利用CIPRA和中国关怀（另一个CDC HIV/AIDS项目）的基础设施，在FPD和1DU人群中识别人口统计学匹配的HIV+和HIV-参与者的大样本（4组，每组n = 200）。在为期5年的研究期间，我们将阐明这些人群中HIV相关NP损伤的患病率、性质、临床意义和变化模式。我们将确定是否NP损伤的差异预测宿主的遗传特征，包括特定的HLA类型和基因编码的趋化因子受体，趋化因子和细胞因子的多态性。还将检查与丙型肝炎病毒（HCV）共病感染的影响，因为HCV是NP损伤的独立风险，在IDU和FPD人群中均高度流行。 该项目扩展了中国和美国调查人员之间的现有关系。在组织层面，美方将负责整体研究进展、培训、质量保证和数据管理，而中方将招募、跟踪和评估参与者。这项研究将为中国艾滋病的神经认知和神经精神并发症提供详细的新信息。这增加了对这些并发症的临床意义及其在中国的决定因素的理解，应更好地为受影响人群的临床管理提供信息。

DESCRIPTION (provided by applicant): Research in Western countries indicates that neuropsychological (NP) impairment is a common consequence of HIV infection and is associated with reduced everyday functioning and worse medical prognosis (early mortality). China (population 1.3 billion) is seeing an exponential growth in its HIV epidemic. Although differences in host genetics, treatment, and cofactors (e.g., other infections) may result in different neurobehavioral outcomes in China, there has been no research on neuroAIDS there. The Chinese government has placed a high priority on HIV prevention and treatment. With support of the U.S. NIH, the China CDC has initiated the China Comprehensive International Program for Research on AIDS (CIPRA), and is beginning a series of studies on two major HIV risk populations in China: injection drug users (IDUs) and former plasma donors (FPDs). Here we propose the first study of HIV related neurobehavioral disorders in China. In collaboration with colleagues at the China CDC, we will utilize the infrastructure of CIPRA and China CARES (another CDC program for HIV/AIDS) to identifiy large samples of demographically matched HIV+ and HIV- participants within the FPD and 1DU populations (4 groups, each with n=200). Over a 5-year study period, we will clarify the prevalence, nature, clinical significance, and patterns of change in HIV associated NP impairments in these groups. We will determine whether differences in NP impairment are predicted by host genetic characteristics, including specific HLA types and polymorphisms in genes encoding for chemokine receptors, chemokines, and cytokines. Effects of comorbid infection with hepatitis C virus (HCV) also will be examined, because HCV is an independent risk for NP impairment and is highly prevalent in both the IDU and FPD populations. This project extends an existing relationship between the Chinese and U.S. investigators. At an organizational level, the U.S. side will be responsible for overall study progress, training, quality assurance, and data management, while the China side will recruit, track and assess participants. The proposed research will provide detailed new information about neurocognitive and neuropsychiatric complications of HIV disease in China. This increased understanding of the clinical significance of these complications and their determinants in China should better inform clinical management of affected populations.