CNS HIV ANTIRETROVIRAL THERAPY EFFECTS RESEARCH (CHARTER)

CNS HIV 抗逆转录病毒治疗效果研究（章程）

• 批准号: 7953662
• 负责人: Susan Morgello
• 金额: $ 6.68万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-03-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7953662
• 关键词: Antiretroviral resistance; Antiviral Agents; Clinical Research; Competence; Computer Retrieval of Information on Scientific Projects Database; Disease; Drug resistance; Funding; Grant; HIV; HIV Infections; Highly Active Antiretroviral Therapy; Impairment; Incidence; Institution; Measures; Nervous system structure; Neurocognitive; Pathogenesis; Patients; Penetration; Peripheral Nervous System Diseases; Pharmaceutical Preparations; Plasma; Prevalence; Protocols documentation; RNA; Recruitment Activity; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Source; Staging; Treatment Protocols; United States; United States National Institutes of Health; Viral; antiretroviral therapy; cognitive function; design; immune RNA; nervous system disorder; neurotoxicity; therapy design

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 随着高效抗逆转录病毒治疗 (HAART) 的出现，HIV 相关神经系统疾病谱发生了变化，但尚未对这些表现及其潜在发病机制进行大规模、全面的研究。该研究被设计为一项针对 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 个亚点的 HIV 感染患者的代表性样本。纵向组成部分，并将招募处于艾滋病毒疾病各个阶段的患者。 假设：HAART 将对 CNS 和 PNS 功能产生不同的影响，具体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 确定与未接受HAART的患者相比，接受HAART的患者是否降低了HIV感染的CNS和PNS并发症的风险曾服用或已停止先前的抗逆转录病毒药物。 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（通过脑脊液 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 HIV 疾病晚期的神经认知损伤机制是否与 HIV 疾病早期的不同。 4 测量中枢神经系统内 HIV 复制（通过脑脊液 HIV RNA 测量）和免疫能力（通过 CD4 水平测量）与 HIV 相关神经认知障碍综合征的患病率和发生率的关系。 图 5 确定了 HIV 血浆和脑脊液中不一致的抗逆转录病毒药物耐药性的发生率。 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 ARV 神经毒性不同。