HIV Dementia and Sensory Neuropathy in Uganda

乌干达的艾滋病毒痴呆症和感觉神经病

• 批准号: 7684134
• 负责人: NED C SACKTOR
• 金额: $ 12.12万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-08 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7684134
• 关键词: AIDS Dementia Complex; AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Affect; Africa South of the Sahara; Age; Alzheimer' s Disease; Anti-Retroviral Agents; Behavioral; CD4 Lymphocyte Count; Cells; Clinic; Clinical; Cognitive; Collaborations; Communicable Diseases; Country; Data; Dementia; Development; Dideoxynucleosides; Disease Progression; Drug usage; Early Diagnosis; Elderly; Epidemic; Epidemiology; Exposure to; Frequencies; Functional disorder; Future; HIV; HIV Infections; HIV diagnosis; HIV-1; Highly Active Antiretroviral Therapy; Immunosuppression; Impaired cognition; Impairment; Individual; Infection; Life; Longitudinal Studies; Measures; Morbidity - disease rate; Motor; Nervous System Physiology; Neurocognitive; Neurologic; Neurologic Manifestations; Neuropathy; Neuropsychological Tests; Patients; Performance; Peripheral Nerves; Peripheral Nervous System; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Plasma; Prevalence; Prospective Studies; Public Health; RNA; Research Infrastructure; Resources; Risk; Risk Factors; Scientist; Symptoms; Tanzania; Training; Treatment Protocols; Uganda; United States; Vascular Dementia; Virulence; antiretroviral therapy; base; clinical practice; cohort; high risk; nervous system disorder; neurovirulence; prevent; public health relevance; research study; sensory neuropathy

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.

描述（由申请人提供）：HIV痴呆（HIV-D）和HIV相关感觉神经病（HIV-SN）是晚期HIV感染最常见的神经系统表现。撒哈拉以南非洲是全球大多数艾滋病毒病例的居住地，该地区的艾滋病毒丁型和艾滋病毒SN型流行率在很大程度上未知。此外，HIV亚型可能对HIV疾病进展有影响，这表明HIV亚型可能在引起神经系统疾病的能力方面有所不同。该项目将在乌干达聚集一批艾滋病毒阳性者：1）确定在具有中度晚期免疫抑制的未经治疗的HIV+个体中HIV-D和HIV-SN的患病率和与HIV-D和HIV-SN相关的风险因素，2）确定未经治疗的HIV+个体的神经心理学测试表现和外周神经功能是否从基线下降，和3）获得初步数据以确定HIV亚型在HIV-D和HIV-SN的风险以及HIV相关的认知障碍和外周神经功能的进展方面是否不同。我们提出了在撒哈拉以南非洲进行的第一个大规模的HIV-D和HIV-SN前瞻性研究。该提案将提供描述HIV-D和HIV-SN的流行和进展所需的数据，这些数据可用于未来的R 01应用。HIV相关的认知功能障碍目前不是HIV+个体（CD 4计数在201-350个细胞/L范围内）开始HAART治疗的指征。我们的提案将提供必要的数据，以确定是否应该改变撒哈拉以南非洲国家（如乌干达）在中度免疫抑制和轻度神经认知障碍的HIV+个体中启动HAART的临床实践参数。我们的建议将检查HIV亚型是否可能在引起HIV相关CNS和PNS功能障碍的能力方面存在差异。该提案还将为乌干达坎帕拉的艾滋病毒临床医生-科学家提供艾滋病毒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，在撒哈拉以南非洲，HIV-D和HIV-SN是经常未被识别的晚期HIV感染并发症，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进行有效治疗。 公共卫生相关性：艾滋病毒痴呆症（HIV-D）和艾滋病毒相关感觉神经病（HIV-SN）在撒哈拉以南非洲的流行病学在很大程度上是未知的，全球大多数艾滋病毒病例居住在那里。该项目将在乌干达聚集一批艾滋病毒阳性者：1）确定在具有中晚期免疫抑制的未经治疗的HIV+个体中HIV-D和HIV-SN的患病率和与HIV-D和HIV-SN相关的风险因素，2）确定未经治疗的HIV+个体的神经心理学测试表现和外周神经功能是否从基线下降，以及3）获得初步数据以确定HIV亚型在HIV-D和HIV-SN的风险方面是否不同。