Prospective Study-Viral/Immune Correlates Pediatric HIV

前瞻性研究——病毒/免疫与儿童艾滋病毒相关

• 批准号: 7006410
• 负责人: NATASCHA CHING
• 金额: $ 13.06万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7006410
• 关键词: AIDS therapy; Brazil; adolescence (12-20); cellular immunity; children; chronic disease /disorder; clinical research; cytotoxic T lymphocyte; disease /therapy duration; helper T lymphocyte; host organism interaction; human immunodeficiency virus 1; human subject; human therapy evaluation; immune response; infant human (0-1 year); longitudinal human study; neutralizing antibody; patient oriented research; pediatric AIDS; virus infection mechanism; virus load; virus replication

DESCRIPTION (provided by applicant): Natascha Ching is a Pediatric Infectious Diseases specialist and Clinical Instructor, proposed Assistant Professor in Pediatrics, at the University of California, Los Angeles. The candidate's career objective is to become an independent investigator in patient oriented research, specializing in pediatric HIV-1 infection. The candidate became interested in the immune reconstitution of Pediatric HIV patients on highly active antiretroviral therapy (HAART) during fellowship. She initiated a prospective evaluation of cellular and humoral immune responses to recall antigens (tetanus booster/Hepatitis A). Based on her preliminary data, she expanded the project by learning a new technique of HIV cytotoxic T lymphocyte (CTL) peptide mapping to evaluate a cross-section of patients in the proposed study population. She detected HIV specific CTL responses in 82% of children and adolescents on HAART (undetectable viral load + HIV viremia). Autologous neutralizing antibody (ANAB) responses were also detected in pediatric HIV patients with prolonged viral suppression on HAART. This proposed career development plan will consist of closely mentored patient oriented research with Yvonne Bryson and Otto Yang as mentors, a structured laboratory evaluation of the clinical population along with a didactic curriculum in UCLA K30 translational research program. Aims: We propose a prospective analysis of the protective immune correlates and viral containment in two well-characterized cohorts of pediatric HIV patients treated with HAART. We hypothesize that differences in the progression of pediatric HIV disease are directly related to variability in host immune pressures including HIV specific cellular immune responses (CDS CTL and CD4 help), ANAB responses and viral diversity and will be altered by initiation of HAART. Subjects: Cohort I is a group of chronically HIV-1 infected children/adolescents on HAART. Cohort II is a group of newly diagnosed perinatally HIV-1 infected infants prospectively randomized to early or deferred HAART, followed over 5 years. HIV specific cellular and humoral immune responses may vary according to the level and durability of virological responses to HAART in cohort I. Early treatment with HAART may contain viral replication, effect viral diversity, and preserve the immune system in cohort II. HIV cellular and humoral immune responses may vary between early vs. deferred treatment groups and by disease progression.

描述（由申请人提供）：Natascha Ching 是加州大学洛杉矶分校儿科传染病专家和临床讲师，拟任儿科助理教授。候选人的职业目标是成为一名以患者为导向的研究的独立研究者，专门研究儿童 HIV-1 感染。该候选人在研究期间对接受高效抗逆转录病毒治疗 (HAART) 的儿童 HIV 患者的免疫重建产生了兴趣。她发起了对细胞和体液免疫反应的前瞻性评估，以回忆抗原（破伤风加强剂/甲型肝炎）。根据她的初步数据，她通过学习 HIV 细胞毒性 T 淋巴细胞 (CTL) 肽图谱新技术来扩展该项目，以评估拟议研究人群中患者的横截面。她在接受 HAART 治疗的 82% 儿童和青少年中检测到 HIV 特异性 CTL 反应（不可检测的病毒载量 + HIV 病毒血症）。在长期接受 HAART 病毒抑制的儿童 HIV 患者中也检测到了自体中和抗体 (ANAB) 反应。这项拟议的职业发展计划将包括由 Yvonne Bryson 和 Otto Yang 作为导师的密切指导的以患者为导向的研究、对临床人群的结构化实验室评估以及 UCLA K30 转化研究项目的教学课程。目的：我们建议对接受 HAART 治疗的两个特征明确的儿科 HIV 患者队列中的保护性免疫相关性和病毒遏制进行前瞻性分析。我们假设，儿科 HIV 疾病进展的差异与宿主免疫压力的变化直接相关，包括 HIV 特异性细胞免疫反应（CDS CTL 和 CD4 帮助）、ANAB 反应和病毒多样性，并将通过启动 HAART 来改变。受试者：第一组是一组接受 HAART 治疗的长期感染 HIV-1 的儿童/青少年。第二组是一组新诊断的围产期 HIV-1 感染婴儿，前瞻性随机接受早期或延迟 HAART 治疗，并随访 5 年以上。 HIV特异性细胞和体液免疫反应可能根据队列I中对HAART的病毒学反应的水平和持久性而变化。在队列II中，早期HAART治疗可能会抑制病毒复制，影响病毒多样性，并保护免疫系统。 HIV细胞和体液免疫反应可能因早期治疗组与延迟治疗组以及疾病进展而异。