NeuroAIDS in India

描述（由申请人提供）：印度的神经艾滋病病毒和宿主因素以及合并症在确定与HIV感染相关的神经系统并发症的易感性方面起着关键作用。大多数关于HIV相关神经认知障碍的研究都是在西方国家进行的，其中HIV进化枝B占主导地位。然而，在世界范围内，进化枝C更为常见，最近的病毒学研究表明，其神经毒力可能不同于进化枝B。在印度，大约有500万人感染了艾滋病毒，其中绝大多数是C型病毒。在本研究中，我们将在印度队列中解决以下目标：1）确定未接受抗逆转录病毒（ARV）治疗的HIV感染者中HIV相关神经认知功能障碍（HNCI）的患病率和性质，2）确定新启动的ARV治疗对认知功能的影响，3）评估病毒相关神经认知功能障碍（HNCI）。（env，达特）与HNCI相关的遗传学，和4）确定HNCI与宿主免疫遗传因子之间的关系（即，基因型MCP-1、CCL 3L 1拷贝数、RANTES和CCR 5/CCR 2中的多态性以定义CCR 5单倍型）。在美国HIV神经行为研究中心（HNRC）和印度浦那国家艾滋病研究所（NARI）合作的基础上，我们建议在相关研究（HPTN 052，印度国家艾滋病控制组织计划）中开始抗逆转录病毒治疗前检查300名HIV阳性个体，此后每年随访一次。我们还将招募一个HIV血清阴性对照组，以建立神经心理学规范，确定个体HIV+患者的损伤。这项研究的可行性已经证明了一个试点研究中，我们创建了马拉地语翻译的文书，培训印度的人员，并检查了60名参与者使用的方法最初在HNRC，但适应印度。该项目将有可能a）导致更好地了解印度C支HIV感染的神经系统并发症的特征和相关性，以及B）通过认知评估、基因组学和生物标志物测定领域的技术转让，增强印度现有的临床和科学专业知识。

DESCRIPTION (provided by applicant): NeuroAIDS in India Viral and host factors, as well as comorbidities, play key roles in determining susceptibility to the neurologic complications associated with HIV infection. Most studies of HIV-related neurocognitive impairment have been conducted in Western countries, where HIV clade B predominates. Worldwide, however, clade C is much more common and recent virologic studies suggest that its neurovirulence may differ from clade B. Approximately 5 million individuals are infected with HIV in India, the vast majority with clade C virus. In the present study we will address the following aims within an Indian cohort: 1) to determine the prevalence and nature of HIV-associated neurocognitive impairment (HNCI) in HIV-infected individuals who are not on antiretroviral (ARV) therapy, 2) to determine the impact of newly-initiated ARV treatment on cognitive functioning, 3) to assess the viral (env, tat) genetics associated with HNCI, and 4) to determine the relationship between HNCI and host immunogenetic factors (i.e., genotype MCP-1, CCL3L1 copy number, RANTES and polymorphisms in CCR5/CCR2 to define CCR5 haplotypes). Building upon collaboration between the HIV Neurobehavioral Research Center (HNRC) in the U.S. and the National AIDS Research Institute (NARI) in Pune, India, we propose to examine 300 HIV+ individuals prior to initiation of ARVs in linked studies (HPTN 052, India National AIDS Control Organization program) and follow them annually thereafter. We will also enroll an HIV seronegative comparison group in order to establish neuropsychological norms for determining impairment in individual HIV+ persons. The feasibility of this study has been demonstrated by a pilot study in which we created Marathi-translated instruments, trained India personnel, and examined 60 participants using methods originally developed at the HNRC but adapted to India. This project will potentially a) lead to improved understanding of the characteristics and correlates of neurologic complications of clade C HIV infection in India and b) enhance existing clinical and scientific expertise in India via technology transfer in the areas of cognitive assessments, genomics, and biomarker assays.