Defining CNS HIV Infection in Treated Patients: Foundation for Eradication

定义接受治疗的患者中枢神经系统 HIV 感染：根除的基础

• 批准号: 8411590
• 负责人: RICHARD W. PRICE
• 金额: $ 16.39万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-01-11 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8411590
• 关键词: AIDS Dementia Complex; Biological Assay; Biological Markers; Central Nervous System Diseases; Central Nervous System Infections; Cerebrospinal Fluid; Characteristics; Chronic; Clinical; Disease; Drug Combinations; Foundations; Frequencies; Future; Genetic; HIV; HIV Infections; Immune; Impairment; Incidence; Individual; Infection; Injury; Measurable; Measurement; Measures; Methods; Natural History; Nervous system structure; Neuraxis; Neurocognitive; Neurologic; Neuropsychological Tests; Patients; Penetration; Performance; Pharmaceutical Preparations; Phylogenetic Analysis; Plasma; Population; RNA; Regimen; Residual state; Sampling; Source; Techniques; Testing; Viral; Viral Load result; Viremia; Virus; antiretroviral therapy; follow-up; functional disability; genome sequencing; immune activation; nerve injury; novel; relating to nervous system; viral RNA; viral detection

DESCRIPTION (provided by applicant): The proposed studies focus on central nervous system (CNS) HIV infection and its consequences in treated patients with plasma viral suppression. In the first of two aims, we will use the ultrasensitive single copy assay (SCA) of viral RNA to define the presence and magnitude of cerebrospinal fluid (CSF) infection in a group of 'well-treated' patients and examine the impact of 'residual' CSF infection on CSF biomarkers of immunoactivation and neural injury and on neuropsychological test performance. We will also assess whether residual CSF infection relates to combination drug penetration characteristics. In the second aim, we will use sensitive single genome sequencing (SGS) methods and phylogenetic relationships to analyze the origins of viral escape and residual CSF HIV in treated patients. While antiretroviral therapy has had a remarkable impact on severe CNS HIV disease, persistent CNS infection in treated patients remains potentially important as the driver of chronic, continued CNS immunoactivation and injury, and as a viral reservoir that needs to be targeted by viral eradication strategies. The proposed studies will provide unique and essential information regarding the frequency, character and consequences of continued CNS HIV infection in 'well-treated' patients and also provide a foundation for eradication strategies targeting this infection.

描述（由申请人提供）： 拟定研究的重点是中枢神经系统（CNS）HIV感染及其对血浆病毒抑制治疗患者的影响。在第一个目标中，我们将使用病毒RNA的超灵敏单拷贝测定（SCA）来确定一组“治疗良好”患者中脑脊液（CSF）感染的存在和程度，并检查“残留”CSF感染对免疫活化和神经损伤的CSF生物标志物以及神经心理学测试性能的影响。我们还将评估残留CSF感染是否与联合药物渗透特征有关。在第二个目标中，我们将使用敏感的单基因组测序（SGS）方法和系统发育关系来分析治疗患者中病毒逃逸和残留CSF HIV的起源。虽然抗逆转录病毒治疗对严重CNS HIV疾病具有显著影响，但治疗患者的持续CNS感染仍然具有潜在的重要性，因为它是慢性持续CNS免疫活化和损伤的驱动因素，也是需要通过病毒根除策略靶向的病毒储存库。拟议的研究将提供关于“良好治疗”患者持续CNS HIV感染的频率、特征和后果的独特和重要信息，并为针对这种感染的根除策略提供基础。