CNS HIV ANTIRETROVIRAL THERAPY EFFECTS RESEARCH (CHARTER)

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 随着高效抗逆转录病毒疗法(HAART)的出现，人们正在观察到艾滋病毒相关神经系统疾病谱的变化。然而，目前还没有大规模的、全面的研究这些表现及其潜在的发病机制。该宪章方案旨在对艾滋病毒和HAART疗法的神经系统并发症进行观察性、非干预性研究，旨在涵盖美国6个子网站具有代表性的艾滋病毒感染患者样本。它将包括横向和纵向两个部分，并将招募艾滋病毒疾病所有阶段的患者。 假设：HAART将对CNS和PNS功能产生不同的影响，这取决于方案的类型和患者特定的因素。病毒复制和耐药性是疾病纵向表现的重要决定因素。 这项研究将： 1-确定服用HAART的患者是否比那些没有接受或已经停止抗逆转录病毒药物的患者降低了艾滋病毒感染的CNS和PNS并发症的风险。 2-确定HAART的中枢神经系统渗透情况是否与中枢神经系统内的抗病毒作用(以脑脊液HIV RNA水平衡量)和HIV相关神经疾病的风险(以认知功能衡量)有关。 3-确定晚期HIV病的神经认知损害机制是否与HIV病早期的不同。 4-衡量中枢神经系统内的艾滋病毒复制(以脑脊液艾滋病毒RNA衡量)和免疫能力(以CD4水平衡量)与综合征性艾滋病毒相关神经认知障碍的流行和发生率的关系。 5-确定HIV血浆和脑脊液中非协调性ARV耐药性的患病率。 6-确定HIV引起的周围神经病的预测因素和危险因素是否不同于d-药物ARV的神经毒性。

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. With the availability of highly active antiretroviral therapy (HAART), shifts in the spectrum of HIV-related nervous system diseases are being observed. However, there has been no large-scale, comprehensive study of these manifestations and their potential pathogenesis. The CHARTER protocol was designed as an observational, non-interventional study of the nervous system complications of HIV and HAART therapy, designed to encompass a representative sample of HIV-infected patients at 6 subsites across the United States. It will have both cross-sectional and longitudinal components, and will recruit patients in all stages of HIV disease. Hypothesis: HAART will have variable effects on CNS and PNS function, dependent upon the type of regimen and patient-specific factors. Viral replication and drug resistance are important determinants in the longitudinal manifestations of disease. This study will: 1 - To determine if patients taking HAART have reduced risk of CNS and PNS complications of HIV infection compared to those who are nanve to or have stopped prior ARV. 2- To determine if the CNS penetration profile of HAART is related to antiviral effects within the CNS (as measured by CSF HIV RNA levels) and to risk of HIV-associated neurological disease (as measured by cognitive function). 3 - To determine if the mechanism of neurocognitive damage in late stage HIV disease differs from that in earlier stages of HIV disease. 4 - To measure the relationship of HIV replication within the CNS (as measured by CSF HIV RNA) and of immune competence (as measured by CD4 levels) to the prevalence and incidence of syndromic HIV-related neurocognitive impairment. 5 - To determine the prevalence of discordant ARV resistance in HIV plasma and CSF. 6 - To determine if the predictors and risk factors for peripheral neuropathy from HIV differ from that of d-drug ARV neurotoxicity.