HIV Clade on Cognitive and Neurological Disorders Brazil

描述（由申请方提供）：HIV-1引起神经认知和神经系统疾病，这些疾病代表了一个公共卫生问题，因为它们给HIV感染患者、其护理人员和医疗保健系统造成了巨大负担。最近的报道表明，进化枝C病毒可能具有降低的神经侵袭能力，因为进化枝C分离物携带编码变体达特蛋白的tat序列，该变体蛋白在体外显示与进化枝B达特相比在单核细胞趋化性方面有缺陷。缺陷的达特趋化因子基序被假设为C-特异性的基础上，从几个国家的分离株，并可以解释在这些国家中的一些报告的艾滋病毒脑受累的发病率较低。然而，没有研究直接比较感染HIV-1分支C和B的个体的神经认知功能。因此，在C分支流行的地区，痴呆症的报告率较低，可能是由于确定偏差，合并感染的患病率差异或其他因素。本申请建议在巴西南部对HIV-1进化枝对神经认知和神经系统疾病的影响进行横断面比较。加州大学圣地亚哥分校的研究人员在神经艾滋病临床研究方面拥有丰富的经验，他们将支持巴西巴拉那州库里蒂巴的研究人员，他们负责照顾大量感染C或B分支的患者。在这种情况下，可以比较分支特异性效应，同时控制潜在的混杂因素，如种族，社会人口特征，HIV感染和合并感染的风险因素。UCSD研究人员将培训和指导临床评估工具的管理和解释，并将技术转移到巴西研究中心。

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.