HIV Clade on Cognitive and Neurological Disorders Brazil

描述(申请人提供)：艾滋病毒-1引起神经认知和神经障碍，这是一个公共卫生问题，因为它们给艾滋病毒感染者、他们的照顾者和医疗保健系统带来了巨大的负担。最近的一份报告表明，C分支病毒可能具有降低的神经侵袭能力，因为C分支分离株携带编码一种变异的TAT蛋白的TAT序列，体外实验表明，与B分支TAT相比，TAT蛋白在单核细胞趋化方面存在缺陷。根据几个国家的分离株，有缺陷的TAT趋化因子基序被假设为C分支特异的，这可以解释其中一些国家报告的艾滋病毒脑参与的较低流行率。然而，还没有研究直接比较感染HIV-1 C和B分支的人的神经认知功能。因此，在C分支流行的地区，痴呆率较低的报道可能是由于确定偏差、合并感染的不同流行程度或其他因素。这项申请建议对艾滋病毒-1分支对巴西南部神经认知和神经障碍的影响进行横断面比较。在神经艾滋病临床研究方面拥有丰富经验的UCSD调查人员将为巴西巴拉那州库里蒂巴的调查人员提供支持，他们照顾大量感染C或B分支的患者。在这种情况下，可以比较特定分支的影响，同时控制潜在的混杂因素，如种族、社会人口特征、艾滋病毒感染的风险因素和联合感染。加州大学圣地亚哥分校的调查人员将培训和指导临床评估仪器的管理和解释，并将技术转移到巴西现场。

DESCRIPTION (provided by applicant): HIV-1 causes neurocognitive and neurological disorders that represent a public health problem as they result in a substantial burden to patients living with HIV infection, their caregivers, and the healthcare system. A recent report suggests that clade C viruses may possess a reduced capacity for neuroinvasion because clade C isolates bear tat sequences coding for a variant Tat protein shown in vitro to be defective in monocyte chemotaxis as compared to clade B Tat. The defective Tat chemokine motif is hypothesized to be clade C-specific based on isolates from several countries and could explain the lower prevalence of HIV brain involvement reported in some of these countries. However, no study has directly compared neurocognitive function among individuals infected with HIV-1 clades C and B. Thus, lower reported rates of dementia in regions where clade C is prevalent may result from ascertainment bias, differential prevalence of co-infections or other factors. This application proposes to perform a cross-sectional comparison of the influence of HIV-1 clade on neurocognitive and neurological disorders in southern Brazil. UCSD investigators, who have extensive experience in NeuroAIDS clinical research, will support investigators in Curitiba, Parana, Brazil, who care for large numbers of patients infected with either clade C or B. In this setting, clade-specific effects can be compared while controlling for potential confounding factors such as ethnicity, sociodemographic characteristics, risk factors for HIV infection and co-infections. UCSD investigators will train and guide the administration and interpretation of the clinical assessment instruments, transfer technology to the Brazilian site.