Neurocognitive Consequences of HIV/AIDS in South India

说明（由申请人提供）：人体免疫缺陷病毒（艾滋病毒）流行病在发展中国家和中低收入国家正以惊人的速度蔓延。使用高效抗逆转录病毒疗法（HAART）治疗艾滋病毒的时间往往被推迟，或许多感染者无法获得治疗，因此，这些国家中艾滋病毒相关疾病的流行率远高于高收入国家。在印度南部，许多患者经历严重的免疫抑制和神经认知和神经影像学异常的发展。针对这些异常演变的初步研究揭示了CD4细胞计数低与认知困难之间的密切关系，以及免疫系统明显抑制的患者中特定脑结构的体积与认知功能障碍之间的关联。然而，研究尚未检查严重受损的免疫系统对非痴呆患者神经认知和神经影像学异常发展的影响。该提案的目的是在印度金奈的YRG Care的临床研究人员和布朗大学艾滋病研究中心的研究人员之间建立合作研究伙伴关系，以检查与艾滋病毒相关的脑功能障碍。我们建议：1)建立调查合作并进行需求评估；2)开发和实施培训模块，重点评估认知功能、结构神经影像学异常，以及疾病活动的认知、神经影像学和实验室值的整合；3)收集试点数据，以便随后提交R01，全面研究HIV患者脑功能障碍的演变。这项初步研究将包括收集免疫系统严重受损的HIV患者的认知、结构MRI和疾病活动的实验室值。横断面和纵向分析将检查艾滋病毒对认知和大脑形态计量指标的影响。该研究将利用印度金奈YRG护理中心现有的基础设施，以及布朗CFAR建立的临床和研究基础设施。这项发展资助将在理解与艾滋病毒相关的脑部疾病方面取得重大进展。

DESCRIPTION (provided by applicant): The human immunodeficiency virus (HIV) epidemic is progressing at an alarming rate in developing and low- to middle-income countries. Treatment of HIV with highly active antiretroviral therapy (HAART) is frequently delayed or unavailable to many infected individuals, and consequently the prevalence of HIV-associated diseases is much higher in these countries compared to high-income countries. In southern India, many patients experience severe immunosuppression and development of neurocognitive and neuroimaging abnormalities. Preliminary studies focused on the evolution of these abnormalities reveal strong relationships between low CD4 cell count and cognitive difficulties, and associations between the volume of specific brain structures and cognitive dysfunction among patients with significant immune system suppression. However, studies have not examined the impact of severely compromised immune systems on the development of neurocognitive and neuroimaging abnormalities among non-demented patients. The purpose of this proposal is to establish a collaborative research partnership between clinical researchers at YRG Care in Chennai, India and researchers at the Brown University Center For AIDS Research to examine brain dysfunction associated with HIV. We propose to: 1) establish the investigative collaboration and conduct needs assessments, 2) develop and implement training modules focused on the assessment of cognitive function, structural neuroimaging abnormalities, and the integration of cognitive, neuroimaging, and laboratory values of disease activity, 3) collect pilot data for a subsequent R01 submission to comprehensively examine the evolution of brain dysfunction in patients with HIV. The pilot study will involve collection of cognitive, structural MRI and laboratory values of disease activity in HIV patients with significant immune system compromise. Cross-sectional and longitudinal analyses will examine the impact of HIV on cognitive and brain morphometric indices. The study will take advantage of the infrastructure currently available at the YRG Care in Chennai, India, and the clinical and research infrastructure established at the Brown CFAR. The developmental grant will yield significant advances in the understanding of brain disorders associated with HIV.