ACTG 736

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。有几个理论上的理由可以预测，脑脊液和大脑中的HIV-1可能在表型和基因表型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，并最终影响神经系统疾病发展的可能性。虽然HIV-1可以在HIV-1疾病的早期在脑脊液（CSF）和大脑中检测到，但脑脊液中定量病毒的重要性和预后价值尚不清楚。关于强效抗逆转录病毒治疗（PART）对CSF HIV水平的影响，仅有有限的数据可用。本研究的总体目标是：确定PART在减少脑脊液中的HIV方面是否与血浆中的HIV一样有效；确定脑脊液和血液之间病毒基因型和药物渗透的差异是否解释了PART在脑脊液室中抑制HIV能力的差异；确定脑脊液中病毒和免疫激活标记物数量的变化与神经心理表现指标之间的关系。主要的具体目的是比较血浆和脑脊液中HIV RNA对PART的抑制程度和持久性。-确定CSF HIV RNA对PART反应的强度和持久性是否与神经心理表现的改善有关。第二个目的是：评价脑脊液药物穿透的药代动力学。-确定CSF HIV RNA反应与基因型和药代动力学估计的关系。-确定CSF HIV RNA对PART反应的强度和持久性是否与CSF免疫激活标记物的改善相对应。-确定脑脊液免疫激活标记物的反应是否与神经心理表现的改善相关。-确定血液中病毒进化与脑脊液室之间的长期关系。接受PART治疗的受试者的免疫状况及认知功能障碍的发展

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