HIV Dementia and Sensory Neuropathy in Uganda

描述(申请人提供)：HIV痴呆(HIV-D)和HIV相关感觉神经病(HIV-SN)是晚期HIV感染最常见的神经学表现。在全球大多数艾滋病毒病例居住的撒哈拉以南非洲地区，艾滋病毒-D和艾滋病毒-SN的流行情况在很大程度上是未知的。此外，艾滋病毒亚型可能对艾滋病毒疾病的进展有影响，这表明艾滋病毒亚型可能在导致神经系统疾病的能力方面有所不同。该项目将在乌干达汇集一组艾滋病毒+个体：1)确定未经治疗的、患有中度晚期免疫抑制的艾滋病毒-D和艾滋病毒-SN的患病率和与艾滋病毒-SN相关的风险因素；2)确定未经治疗的艾滋病毒-D和艾滋病毒-SN个体的神经心理测试成绩和周围神经功能是否在基线水平上下降；3)获得初步数据，以确定艾滋病毒亚型在艾滋病毒-D和艾滋病毒-SN的风险以及与艾滋病毒相关的认知损害和周围神经功能的进展方面是否有所不同。我们提出了撒哈拉以南非洲第一个关于HIV-D和HIV-SN的大规模前瞻性研究之一。这项提案将提供必要的数据，以描述艾滋病毒-D和艾滋病毒-SN的流行和进展情况，这些数据可用于未来的R01应用。艾滋病毒相关性认知障碍目前不是艾滋病毒阳性患者启动抗逆转录病毒治疗的指征，这些患者的CD_4细胞数在201-350个/L之间。我们的提案将提供必要的数据，以确定在撒哈拉以南非洲国家，如乌干达，是否应该改变在中度免疫抑制和轻度神经认知障碍的HIV+患者中启动HAART的临床实践参数。我们的提案将研究HIV亚型是否可能在导致HIV相关的CNS和PNS功能障碍方面有所不同。该提案还将为乌干达坎帕拉的艾滋病毒临床医生和科学家提供艾滋病毒相关神经疾病研究方面的培训。根据我们的初步数据，我们认为，在撒哈拉以南非洲，艾滋病毒-D和艾滋病毒-SN往往是晚期艾滋病毒感染的未被认识到的并发症，是乌干达艾滋病毒+患者发病的一个重要原因，如果及早发现，可以通过抗逆转录病毒治疗和对症治疗有效地治疗。 公共卫生相关性：全球大多数艾滋病毒病例居住的撒哈拉以南非洲地区的艾滋病毒痴呆症(艾滋病毒-D)和艾滋病毒相关感觉神经病(艾滋病毒-SN)的流行病学在很大程度上是未知的。该项目将在乌干达汇集一组艾滋病毒感染者：1)确定未经治疗的中晚期免疫抑制艾滋病毒感染者中艾滋病毒-D和艾滋病毒-SN的患病率和相关风险因素；2)确定未经治疗的艾滋病毒-D和艾滋病毒-SN患者的神经心理测试成绩和周围神经功能是否较基线有所下降；以及3)获得初步数据，以确定艾滋病毒亚型在感染艾滋病毒-D和艾滋病毒-SN的风险方面是否有所不同。

DESCRIPTION (provided by applicant): HIV dementia (HIV-D) and HIV-associated sensory neuropathy (HIV-SN) are the most common neurological manifestations of advanced HIV infection. The prevalence of HIV-D and HIV-SN in Sub- Saharan Africa where the majority of HIV cases reside globally is largely unknown. In addition, HIV subtype may have an impact on HIV disease progression, suggesting the possibility that HIV subtypes may differ with respect to their ability to cause neurological disease. The project will assemble a cohort of HIV+ individuals in Uganda: 1) to determine the prevalence of and risk factors associated with HIV-D and HIV-SN among untreated HIV+ individuals with moderate advanced immunosuppression, 2) to determine whether untreated HIV+ individuals decline from baseline in neuropsychological test performance, and peripheral nerve function, and 3) to obtain preliminary data to determine whether HIV subtypes differ with respect to the risk of HIV-D and HIV-SN, and progression of HIV-associated cognitive impairment and peripheral nerve function. We propose one of the first large scale prospective studies of HIV-D and HIV-SN in Sub-Saharan Africa. This proposal will provide the data necessary to characterize the prevalence and progression of HIV-D and HIV-SN, which could be used for future R01 applications. HIV-associated cognitive impairment is currently not an indication for HAART initiation in HIV+ individuals with a CD4 count in the 201-350 cells/¿L range. Our proposal will provide the data necessary to determine if clinical practice parameters for the initiation of HAART among HIV+ individuals with moderate immunosuppression and mild neurocognitive impairment should be changed in countries within Sub-Saharan Africa such as Uganda. Our proposal will examine whether HIV subtypes may differ with respect to their ability to cause HIVassociated CNS and PNS dysfunction. The proposal will also provide training for the HIV clinician-scientists in Kampala, Uganda in research studies of HIV-associated neurological disease. Based upon our preliminary data, we believe that HIV-D and HIV-SN are frequently unrecognized complications of advanced HIV infection in Sub-Saharan Africa, and are a significant cause of morbidity in HIV+ individuals in Uganda, which if identified early, can be treated effectively with antiretroviral therapy and symptomatic therapies. PUBLIC HEALTH RELEVANCE: The epidemiology of HIV dementia (HIV-D) and HIV-associated sensory neuropathy (HIV-SN) in Sub-Saharan Africa where the majority of HIV cases reside globally is largely unknown. The project will assemble a cohort of HIV+ individuals in Uganda: 1) to determine the prevalence of and risk factors associated with HIV-D and HIV-SN among untreated HIV+ individuals with moderate-advanced immunosuppression, 2) to determine whether untreated HIV+ individuals decline from baseline in neuropsychological test performance, and peripheral nerve function, and 3) to obtain preliminary data to determine whether HIV subtypes differ with respect to the risk of HIV-D and HIV-SN.