ACTG 736

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。有几个理论上的原因可以预期，CSF和大脑中的HIV-1可能与血液中的病毒在表型和基因型上不同，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生的可能性。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，但定量CSF中病毒的重要性和预后价值仍不清楚。关于强效抗逆转录病毒治疗（PART）对CSF HIV水平的影响，数据有限。本研究的总体目标是：确定PART在降低CSF中HIV水平方面是否与血浆中一样有效;确定CSF和血液之间病毒基因型和药物渗透的差异是否是PART抑制CSF中HIV能力差异的原因：确定脑脊液中病毒量和免疫激活标志物的变化与神经心理学指标的关系性能主要具体目的是比较PART对血浆和CSF中HIV RNA的抑制程度和持久性。- 确定CSF HIV RNA对PART反应的幅度和持久性是否与神经心理学表现改善相关。次要目的是：评价CSF药物渗透的药代动力学。- 确定CSF HIV RNA应答与基因型和药代动力学估计值的相关性。- 确定CSF HIV RNA对PART应答的幅度和持久性是否与CSF免疫活化标志物的改善相对应。- 以确定CSF免疫活化标志物中的应答是否与神经心理学表现的改善相关。- 以确定血液和CSF隔室中病毒演变之间的长期关系。接受PART的受试者的免疫状态和认知障碍的发展

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