CNS HIV ANTIRETROVIRAL THERAPY EFFECTS RESEARCH (CHARTER)

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。CHARTER方案设计为HIV和HAART治疗的神经系统并发症的观察性、非干预性研究，旨在涵盖美国6个分中心的HIV感染患者的代表性样本。 它将有横向和纵向两个组成部分，并将招募艾滋病毒疾病各个阶段的患者。 假设：HAART对CNS和PNS功能有不同的影响，取决于治疗方案的类型和患者特异性因素。 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确定与那些未接受过或已停止既往ARV的患者相比，接受HAART的患者是否降低了HIV感染的CNS和PNS并发症的风险。 2确定HAART的CNS渗透特征是否与CNS内的抗病毒作用（通过CSF HIV RNA水平测量）和HIV相关神经系统疾病的风险（通过认知功能测量）相关。 3确定晚期HIV疾病的神经认知损伤机制是否与早期HIV疾病不同。 4测量CNS内HIV复制（通过CSF HIV RNA测量）和免疫能力（通过CD 4水平测量）与综合征型HIV相关神经认知损害的患病率和发生率的关系。 5确定HIV血浆和CSF中不一致的ARV耐药的流行率。 6确定HIV周围神经病变的预测因子和危险因素是否与d-药物ARV神经毒性不同。

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 determine if patients taking HAART have reduced risk of CNS and PNS complications of HIV infection compared to those who are na¿ve to or have stopped prior ARV. 2 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 determine if the mechanism of neurocognitive damage in late stage HIV disease differs from that in earlier stages of HIV disease. 4 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 determine the prevalence of discordant ARV resistance in HIV plasma and CSF. 6 determine if the predictors and risk factors for peripheral neuropathy from HIV differ from that of d-drug ARV neurotoxicity.