Variation in Neurocognitive Impairment of HIV Ugandan Children by HIV Subtype

描述(申请人提供)：撒哈拉以南非洲地区越来越多的艾滋病毒感染儿童现在从抗逆转录病毒治疗中受益，但目前世卫组织和国家抗逆转录病毒(ARV)启动指南将免疫功能应激障碍(CD4%和机会性感染的发生)作为开始治疗的指征。在撒哈拉以南非洲，艾滋病毒造成的神经发育延迟的程度存在相互矛盾的数据。在撒哈拉以南非洲地区高频率的共病以及不同的艾滋病毒亚型如何影响疾病进程方面存在不确定性。值得注意的是，疟疾等并存疾病众所周知会影响儿童的发展，除非加以考虑，否则可能会扭曲艾滋病毒和神经认知障碍之间的联系。对于HIV感染的儿童，由于CD4%过高而推迟治疗，尚不清楚什么可以预测重大的神经发育并发症，或者一旦表现出来，这种损害是否可以通过ARV治疗完全可逆。目前的应用利用了位于乌干达坎帕拉的Makerere大学/加州大学旧金山分校联合疟疾研究项目的现有儿科队列和基础设施，以及乌干达和美国的神经医学、行为和实验室专业知识，以研究在疟疾共同发生的背景下推迟抗逆转录病毒治疗的神经发育后果。我们将在病毒基因特异性水平和HIV DNA病毒载量(两者都是从干血斑点(DBS)确定的)和对过去疟疾暴露的估计作为HIV相关神经发育延迟的新预测因子来评估HIV亚型组成。此外，据我们所知，这将是第一次尝试在一项研究下使用统一的工具来分析和对比艾滋病毒和疟疾相关的神经认知功能障碍。当这些研究完成后，我们将对HIV神经认知障碍的决定因素有更好的理解，无论是在治疗初期还是在治疗患者中。此外，我们将拥有必要的初步数据和工具，以进行明确的前瞻性研究，其中包括关于疟疾合并感染、病毒亚型和其他生物标记物的信息，以规划解决感染艾滋病毒的非洲儿童神经发育延迟的干预性研究。这些研究具有相关性，因为它们有可能改变发展中国家的儿童艾滋病毒治疗模式，并减轻个人和社会神经发育障碍的负担。艾滋病毒感染会影响成人和儿童的大脑功能。在这项研究中，我们将试图确定乌干达有多少艾滋病毒可以改变儿童的大脑发育，可以用什么来预测哪个孩子会出现这种并发症，以及抗艾滋病毒治疗是否可以阻止这种情况。

DESCRIPTION (provided by applicant): Increasing numbers of HIV infected children in Sub-Saharan Africa now benefit from treatment with antiretroviral therapy but current WHO and national guidelines for antiretroviral (ARV) initiation stress impairment of immune function (CD4% and the occurrence of opportunistic infections) as indications for starting treatment. There are conflicting data on the magnitude of the neuro-developmental delay due to HIV in sub- Saharan Africa. Uncertainty exists on how the high frequency of co-morbidities and how different HIV subtypes prevalent in sub-Saharan Africa might impact disease course. Of note co-morbidities such as malaria are well known to impact child development and unless accounted for, may distort associations between HIV and neurocognitive impairment. For HIV infected children deferring therapy because of high CD4%, it is not known what might predict significant neuro-developmental complications or whether, once manifest, whether such impairment is fully reversible with ARV therapy. The current application utilizes existing pediatric cohorts and infrastructure at the Makerere University/UCSF Joint Malaria Study project in Kampala, Uganda and neuro- medical, behavioral and laboratory expertise in Uganda and in the U.S. to study the neuro-developmental consequences of deferred ARV therapy in the background of co- incident malaria. We will assess HIV subtype composition at the viral gene specific level and HIV DNA viral load, (both determined from dried blood spots (dbs)) and estimates of past malaria exposure as novel predictors of HIV related neuro-developmental delay. Additionally, this will be, to our knowledge, the first attempt to analyze and contrast HIV and malaria related neurocognitive dysfunction using uniform tools under one study. When these studies are complete we will have an improved understanding of the determinants of HIV neurocognitive impairment in both treatment na¿ve and on treatment patients. Furthermore, we will have the necessary preliminary data and tools to pursue definitive, prospective studies that include information on malaria co-infection, viral subtype and other biomarkers in planning interventional studies that address neuro- developmental delay in HIV infected African children. These studies are relevant because they have the potential to alter pediatric HIV treatment paradigms in the developing world and to ameliorate the burden of individual and societal neuro- developmental disability. HIV infection can affect the brain function of adults and children. In this study, we will try to determine how much HIV in Uganda can alter the brain development in children what can be used to predict which child will have this complication and whether anti-HIV treatment prevents this.