"CNS HIV ANTI-RETROVIRAL THERAPY EFFECTS OF RESEARCH" (CHARTER)

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。CHARTER的首要目标是采用经过验证的可靠评估方法，以确定现代抗逆转录病毒治疗方法背景下艾滋病毒感染的神经生物学和神经行为并发症的患病率和特征。这些措施包括使用联合抗逆转录病毒药物（“高度活性抗逆转录病毒治疗”或“HAART”），以及新出现的治疗方法，如程序性中断治疗、使用免疫疗法和可能提供的特定神经保护剂。此外，将对选定的“感兴趣”组进行随访，以深入了解神经生物学和神经行为结果，作为对治疗的病毒学和免疫学反应的函数，可用于渗透到中枢神经系统（CNS）的药物的可用性，以及各种抗逆转录病毒治疗方案的过去和现在的经验。为了继续推进我们对神经发病机制和早期发现的理解，以及开发可能为未来研究这些问题提供信息的信息，CHARTER建议采用特定方法纵向检查受试者亚组，这些方法可以在选定的病例中阐明代谢/脂质紊乱（以及这些对CNS/PNS的影响）、结构和功能脑成像、病毒基因组学研究和群体药代动力学研究。为了实现这些目标并解决CHARTER方案中列举的科学目标，我们的研究中心将准备开始在横断面研究中每年每个研究中心每年招募预期的67名HIV+个体，持续4年（整个6个研究中心的研究总数n= 1，600）。每年，每家临床试验机构将在纵向发病机制研究中选择约25例病例进行长期随访（6家临床试验机构研究共计n=600）。根据CHARTER方案中描述的HAART时代对纵向数据的特定需求，选择这些病例，以回答有关HIV CNS疾病的某些关键问题。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The overarching aim of CHARTER is to employ validated reliable assessment methodologies to ascertain the prevalence and characteristics of neurobiological and neurobehavioral complications of HIV infection in the context of modern anti-retroviral (ARV) treatment approaches. These include the use of combination ARV ("highly actively antiretroviral treatment" or "HAART"), as well as the emerging treatment methodologies such as programmed interruption of treatment, the use of immunotherapies, and the possible availability of specific neuroprotective agents. In addition, selected groups "of interest" will be followed longitudinaly in order to gain insights into neurobiological and neurobehavioral outcomes as a function of virologic and immunologic response to treatment, the availability of drugs to penetate into the central nervous system (CNS), and past and present experience with various antiretroviral regimens. To continue to advance our understanding into mechanisms and early detection of neuropathogenesis, as well as to develop information that may inform future research into these questions, CHARTER proposes to examine longitudinally subgroups of subjects with specific methodologies that can shed light on metabolic/lipid disturbances in selected cases (and the CNS/PNS impacts of these), structural and functional brain imaging, viral genomics studies, and studies of population pharmacokinetics. To accomplish these goals and to address the scientific aims enumerated in the CHARTER protocol, our site will be prepared to commence accrual of an anticipated 67 HIV+ individuals annually per site per year for four years into the Cross-Sectional Study (total for entire 6 site study n=1,600). Each year, each site will select approximately 25 cases for long-term follow-up in the Longitudinal Pathogenesis Study (total for 6 site study n=600). These cases will be selected on the basis of there being a specific need for longitudinal data to answer certain critical questions about HIV CNS disease in the era of HAART as described in the CHARTER protocol.