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: 8134496
• 负责人: CRISTIAN L ACHIM
• 金额: $ 39.8万
• 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/8134496
• 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. PUBLIC HEALTH RELEVANCE: Millions of patients are at risk of developing HIV-associated neurocognitive disorders (HAND). We have identified a unique patient cohort that could help in deciphering the risk factors associated with HAND. The overarching hypothesis is that HAND will continue to be prevalent in the long term surviving young adults on HAART and it will have a significant impact on their lives.

描述（由申请人提供）：此R 01申请建立在一个成功的R21赠款的基础上，该赠款检查了一组罗马尼亚青少年和年轻人，他们是长期的艾滋病毒幸存者，尽管经过十多年的有效治疗，但仍然表现出神经心理障碍（约10年）。50%的受试者）。这项研究下一阶段的关键特征是，这些青少年晚期和20岁出头的HIV+病例，他们在很久以前被肠胃外感染，我们有广泛的纵向生物学和治疗信息，可能会经历大脑成熟的改变，可能有神经认知和社会认知后遗症。在1989年以前，罗马尼亚向世界卫生组织报告的艾滋病病例只有13例，而到1990年底，报告的病例有1168例，其中1094例是13岁以下的儿童。在这些机构中传播的HIV的遗传特征显示，所有儿童都感染了HIV分支F1 SA#1：研究HAART长期存活的HIV+患者队列的神经医学（NM）特征，并将其与HAND特征进行比较。我们将研究过去和现在NM数据之间的关系，包括CD 4计数，VL，HAART和HAND相关元素，如：NP损伤，日常功能，风险行为，治疗依从性和精神病合并症。 SA#2：研究从儿童早期感染进化枝F的长期存活者中与HAND相关的病毒遗传因素。我们将在体外对患者病毒分离株的嗜神经性潜力进行测序和测试，并从有或没有HAND的受试者的CSF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（“脑特征序列”）。我们在罗马尼亚队列中的研究提供了一个独特的机会，使宿主免疫，病毒，治疗，共病因素和HAND之间的预后相关性，这些年轻人从小就感染艾滋病毒，通常在大脑发育的最早阶段被感染。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。 公共卫生相关性：数百万患者面临发展为HIV相关神经认知障碍（HAND）的风险。我们已经确定了一个独特的患者队列，可以帮助破译与手相关的风险因素。总体假设是，HAND将继续在HAART长期存活的年轻人中流行，并将对他们的生活产生重大影响。