ACTG 736

ACTG 736

• 批准号: 7378788
• 负责人: JUSTIN CHARLES. MCARTHUR
• 金额: $ 0.11万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378788
• 关键词: ACTG; 736

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. There are several theroetical reasons to expect that HIV-1 in CSF and the brain may be phentopypically and genotypically distinct from viruses in blood, and that these differences may impact the response to therapy and ultimately the likelihood that neurologic disease will develop. Although HIV-1 can be detected in cerebrospinal fluid (CSF) and the brain early in the course of HIV-1 disease, the importance and prognostic value of quantifying virus in the CSF remains unclear. Only limited data are availabe regarding the effect of potent antiretroviral therapy (PART) on CSF HIV levels. The overall goals of this study are: to determine if PART is as effective in reducing HIV in the CSF as it is in plasma; to dteremine whether differences in viral genotype and drug penetration between CSF and blood account for differences in ability of PART to suppress HIV in the CSF compartmetn: to determine the relationship between changes in teh amount of virus andimmune activation markers in CSF and measures of neuropsychological performance. The Primary specific aims are to compare the magnitude and durability of suppression of HIV RNA in the plasma and CSF in response to PART. - to determine if the magnitude and durability of CSF HIV RNA response to PART is associated with improved neuropsychological performance. The secondary aims are to: evaluate the pharmacokinetics of CSF drug penetration. - to determine the association of CSF HIV RNA response with genotype and pharmacokinetic estimates. - to determine if the magnitude and durability of CSF HIV RNA response to PART corresponds with improvement in CSF immune activation markers. - to determine if the response in CSF immune activation markers correlates with improvement in neuropsychological performance. - to determine the long-term relationship between viral evolution in blood and CSF compartmetns. The immune status, and development of cognitive impairment in subjects receiving PART

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。有几个理论理由可以预期，脑脊液和大脑中的HIV-1可能在表型和基因上与血液中的病毒不同，这些差异可能会影响对治疗的反应，并最终影响神经疾病发展的可能性。虽然在HIV-1病程的早期就可以在脑脊液和脑中检测到HIV-1，但定量检测脑脊液中的病毒的重要性和预后价值仍不清楚。关于有效的抗逆转录病毒治疗(部分)对脑脊液艾滋病毒水平的影响，只有有限的数据可用。本研究的总体目标是：确定PART在降低脑脊液中的HIV含量方面是否与在血浆中一样有效；确定PART在脑脊液中抑制HIV的能力差异是否与脑脊液和血液中病毒基因型和药物渗透率的差异有关；确定脑脊液中病毒和免疫激活标志物的变化与神经心理功能指标之间的关系。主要的具体目标是比较部分反应对血浆和脑脊液中HIV RNA抑制的幅度和持久性。-确定脑脊液HIV RNA对部分反应的幅度和持久性是否与神经心理表现的改善有关。次要目的是：评价脑脊液药物渗透的药代动力学。-确定脑脊液HIV RNA反应与基因型和药代动力学估计的关系。-确定部分脑脊液HIV RNA反应的大小和持久性是否与脑脊液免疫激活标志物的改善相对应。-确定脑脊液免疫激活标志物的反应是否与神经心理表现的改善有关。-确定血液中的病毒进化与脑脊液隔膜之间的长期关系。受试者的免疫状态及认知功能障碍的发展