HIV Dementia and Sensory Neuropathy in Uganda

描述（由申请人提供）：HIV痴呆（HIV- d）和HIV相关感觉神经病变（HIV- sn）是晚期HIV感染最常见的神经系统表现。HIV- d和HIV- sn在撒哈拉以南非洲的流行情况在很大程度上是未知的，而撒哈拉以南非洲是全球大多数HIV病例的居住地。此外，艾滋病毒亚型可能对艾滋病毒疾病进展有影响，这表明艾滋病毒亚型可能在引起神经系统疾病的能力方面有所不同。该项目将在乌干达召集一批艾滋病毒感染者：1)确定未治疗的HIV+中度晚期免疫抑制个体中HIV- d和HIV- sn的患病率及其相关危险因素；2)确定未治疗的HIV+个体的神经心理测试成绩和周围神经功能是否较基线下降；3)获得初步数据，以确定HIV亚型在HIV- d和HIV- sn的风险方面是否存在差异。以及hiv相关认知障碍和周围神经功能的进展。我们建议在撒哈拉以南非洲进行HIV-D和HIV-SN的首次大规模前瞻性研究之一。该提案将提供表征HIV-D和HIV-SN的流行和进展所需的数据，可用于未来的R01应用。目前，在CD4细胞计数在201-350细胞/ L范围内的HIV+个体中，HIV相关的认知障碍并不是HAART启动的指征。我们的建议将提供必要的数据，以确定是否应该改变撒哈拉以南非洲国家（如乌干达）中患有中度免疫抑制和轻度神经认知障碍的HIV+个体启动HAART的临床实践参数。我们将研究HIV亚型在引起HIV相关中枢神经系统和PNS功能障碍的能力方面是否存在差异。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相关神经系统疾病研究方面的培训。根据我们的初步数据，我们认为HIV- d和HIV- sn是撒哈拉以南非洲晚期HIV感染的常见并发症，也是乌干达HIV+个体发病的重要原因，如果早期发现，可以通过抗逆转录病毒治疗和对症治疗有效治疗。

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.