Long Term Effects of Chronic HIV Infection on the Developing Brain

慢性艾滋病毒感染对发育中的大脑的长期影响

• 批准号: 8469915
• 负责人: CRISTIAN L ACHIM
• 金额: $ 35.07万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-16 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8469915
• 关键词: 13 year old; Acquired Immunodeficiency Syndrome; Adolescent; Age; Anti-Retroviral Agents; Behavior; Behavior Therapy; Biological; Brain; CD4 Lymphocyte Count; Characteristics; Child; Childhood; Chronic; Code; Comorbidity; DNA; Data; Development; Disease; Drug resistance; Elements; Enrollment; Future; Genetic; Grant; HIV; HIV Infections; HIV Long-Term Survivors; Immune; Impairment; Individual; Infection; Institution; Laboratories; Life; Long-Term Effects; Long-Term Survivors; Machine Learning; Neurocognitive; Neurologic; Neuropsychology; Outcome; Patients; Peripheral Blood Mononuclear Cell; Phylogenetic Analysis; Plasma; Recording of previous events; Relative (related person); Reporting; Risk; Risk Behaviors; Risk Factors; Romania; Staging; Techniques; Teenagers; Time; Viral; Viral Load result; cohort; daily functioning; early childhood; effective therapy; experience; follow-up; genetic element; in vitro testing; interest; nervous system disorder; neuropsychological; neurotropic; prognostic; social cognition; treatment adherence; virus genetics; young adult

DESCRIPTION (provided by applicant): This R01 application builds upon a successful R21 grant that examined a cohort of Romanian adolescents and young adults who are long-term HIV survivors and who, despite over a decade of effective treatment, still demonstrate neuropsychological impairments (approx. 50% of subjects). The key feature of the next stage of this study is that these late teens and early 20s HIV+ cases, who were parenterally infected a long time ago, and for whom we have extensive longitudinal biological and treatment information, may experience altered maturation of the brain, with possible neurocognitive and social cognition sequelae. Prior to 1989, only 13 AIDS cases from Romania had been reported to the WHO, while by the end of 1990, 1168 cases were reported, of which 1094 were in children less than 13 years of age. Genetic characterization of the HIV circulating in these institutions revealed that all the children were infected with HIV clade F1 SA#1: Study the neuromedical (NM) characteristics of a long-term surviving cohort of HIV+ patients on HAART and compare them to the HAND features. We will examine the relationship between past and present NM data, including CD4 counts, VL, HAART and HAND-associated elements like: NP impairment, daily functioning, risk behavior, treatment adherence and psychiatric comorbidities. SA#2: Study the viral genetic factors associated with HAND in long-term survivors infected with clade F since early childhood. We will sequence and test in vitro the neurotropic potential of patient viral isolates and identify conserved viral genetic elements ('brain signature sequences') in the env (C2-V3) coding region, from HIV DNA extracted from the CSF and PBMC of subjects with or without HAND. Our study in the well-characterized Romanian cohort offers a unique opportunity to make prognostic correlations between host immune, viral, treatment, comorbid factors, and HAND in young adults who are living with HIV since childhood, most often being infected during the earliest stages of brain development. As these individuals mature, it will be important to understand the implications of neurocognitive impairment on their future behaviors.

描述（由申请人提供）：此 R01 申请建立在一项成功的 R21 拨款的基础上，该拨款检查了一群长期艾滋病毒幸存者的罗马尼亚青少年和年轻人，尽管经过了十多年的有效治疗，但仍然表现出神经心理障碍（约. 50% 的科目）。这项研究下一阶段的关键特征是，这些十几岁和二十岁出头的艾滋病毒阳性病例，他们很久以前就被肠外感染，我们对他们有广泛的纵向生物学和治疗信息，可能会经历大脑成熟度的改变，可能有神经认知和社会认知后遗症。 1989年之前，罗马尼亚只向世界卫生组织报告了13例艾滋病病例，而到1990年底，已报告了1168例病例，其中1094例是13岁以下儿童。这些机构中传播的 HIV 的遗传特征显示，所有儿童都感染了 HIV 分支 F1 SA#1：研究接受 HAART 治疗的长期存活 HIV+ 患者队列的神经医学 (NM) 特征，并将其与 HAND 特征进行比较。我们将检查过去和现在的 NM 数据之间的关系，包括 CD4 计数、VL、HAART 和 HAND 相关元素，例如：NP 损伤、日常功能、风险行为、治疗依从性和精神合并症。 SA#2：研究自幼儿期感染 F 分支的长期幸存者中与 HAND 相关的病毒遗传因素。我们将在体外对患者病毒分离株进行测序和测试其神经营养潜力，并从受试者脑脊液和 PBMC 中提取的 HIV DNA 中鉴定 env (C2-V3) 编码区中的保守病毒遗传元件（“大脑特征序列”）。或没有手。我们对罗马尼亚队列的研究提供了一个独特的机会，可以在自童年起就感染艾滋病毒的年轻人中建立宿主免疫、病毒、治疗、共病因素和 HAND 之间的预后相关性，这些年轻人通常是在艾滋病毒感染的最早阶段被感染。大脑发育。随着这些人的成熟，了解神经认知障碍对其未来行为的影响非常重要。