Central auditory deficits associated with HIV infection and treatment

 描述(由申请人提供)：我们正在坦桑尼亚进行的由NIDCD资助的研究结果表明，HIV+成人和儿童的主要听力问题是在中枢神经系统。这些缺陷可能与艾滋病毒相关的神经认知障碍(HAND)的原因相同(即由于对中枢神经系统通路的影响)。这些数据还表明，中枢听觉处理的听力学测试可能是研究和跟踪艾滋病毒感染和艾滋病毒治疗对中枢神经系统影响的有用工具。但是，没有数据将中枢听觉过程的听力学测试结果与认知功能的标准测量结果联系起来。此外，目前还不清楚这些测试是否会比现有的测试更敏感，或者能更早地发现神经并发症。由于这些听力测试通常标准化程度很高，而且易于执行，它们可能会提供更好的方法来检测HIV+患者的神经功能障碍。这项拟议研究的目的是评估坦桑尼亚达累斯萨拉姆传染病中心建立的、经过充分研究的HIV+和HIV-成人和儿童队列中的中枢听觉处理(例如，间隙检测阈值、噪声中语音阈值、交错的海绵词测试结果和复杂的听觉脑干反应)。听觉测试的结果将与认知测试(T.O.V.A.和CogState电池)的结果以及炎症标志物水平(IL-6，sCD14)相关联，并随着时间的推移进行跟踪。听力学测试方案与神经认知测试结果和炎症标志物水平的组合--所有这些都是纵向跟踪的--将提供一个强大的组合，以评估随着时间的推移中枢神经并发症的出现和进展。我们的研究将使用笔记本电脑听力测试系统，其中包括：母语问卷管理，以评估自我报告的听力能力和接触噪音、药物和毒素；阈值测听，以评估整体听力；自适应间隙检测测试，以衡量时间处理；斯瓦希里语的言语噪声中测试，以评估言语感知；鼓室测试，以确定中耳状态；斯瓦希里语的交错海绵单词测试，以评估双耳语音处理。评估听觉处理的复杂听觉脑干反应措施将使用专用商业诱发电位系统(Smart-EP)进行。HIV-和HIV+的成年人和儿童将被登记，并通过以中枢听觉处理为重点的方案以及使用T.O.V.A.和CogState测试组进行的神经认知功能测试进行纵向研究。将采集血浆进行sCD14和IL-6分析。听力测试系统与坦桑尼亚有研究经验的大容量诊所的结合，将提供一个极好的环境，以确认和扩大关于艾滋病毒感染的中枢听觉处理缺陷的知识，并确定这些发现是如何相关的。 神经认知发现和炎症。

 DESCRIPTION (provided by applicant): Results from our ongoing NIDCD-funded study in Tanzania in show that the main auditory problems in HIV+ adults and children are in the central nervous system. These deficits likely develop for the same reasons as HIV associated neurocognitive disorder (HAND) (i.e. due to effects on central nervous system pathways). These data also suggest that audiological tests of central auditory processing may be useful tools to study and track the effects of HIV infection and HIV treatment on the central nervous system. But, no data exist that correlate the results of audiological tests of central auditory processes and standard measures of cognitive function. Also, it is not known if these tests would be more sensitive or provide earlier detection of neurological complications than existing tests. Since these audiological tests are often well-standardized and easy to perform, they may offer improved ways to detect neurological dysfunction in HIV+ patients. The objective of the proposed study is to assess central auditory processing (e.g. gap detection thresholds, speech-in-noise thresholds, staggered spondaic word test results, and complex auditory brainstem response) in an established, well-studied, cohort of HIV+ and HIV- adults and children at the Infectious Disease Center in Dar es Salaam, Tanzania. The results from the auditory tests will be correlated with results from cognitive testing (T.O.V.A. and Cogstate batteries) as well as inflammatory marker levels (IL-6, sCD14), and followed over time. The combination of the audiological testing protocol with neurocognitive test results and inflammatory marker levels--all followed longitudinally--will provide a powerful combination to assess the appearance and progression of central neurological complications over time. Our study will use a laptop-based hearing testing system that includes: native-language questionnaire administration to assess self-reported hearing capability and exposure to noise, drugs and toxins; threshold audiometry to assess overall hearing ability; adaptive gap detection testing to measure temporal processing; speech-in-noise testing in Kiswahili to assess speech perception; tympanometry to determine middle ear status; staggered spondaic word testing in Kiswahili to assess binaural speech processing. Complex auditory brainstem response measures to assess auditory processing will be done with a dedicated commercial evoked potential system (Smart-EP). HIV- and HIV+ adults and children will be enrolled, and studied longitudinally with both a central-auditory- processing-focused protocol and tests of neurocognitive function using the T.O.V.A. and Cogstate test battery. Plasma will be collected for analysis for sCD14 and IL-6. The combination of the hearing testing systems with the research-experienced, high-volume clinic in Tanzania, will provide an excellent environment to confirm and expand knowledge about the central auditory processing deficits in HIV infection, and ascertain how these findings are related to neurocognitive findings and inflammation.