Prospective Study-Viral/Immune Correlates Pediatric HIV

描述（由申请人提供）：Natascha Ching是洛杉矶加州大学的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独立的研究人员，以患者为导向的研究，专门从事儿科HIV-1感染。候选人在研究期间对接受高效抗逆转录病毒治疗（HAART）的儿童艾滋病患者的免疫重建产生了兴趣。她启动了对回忆抗原（破伤风加强剂/甲型肝炎）的细胞和体液免疫应答的前瞻性评价。基于她的初步数据，她通过学习一种新的HIV细胞毒性T淋巴细胞（CTL）肽图谱技术来扩展该项目，以评估拟议研究人群中的患者横截面。她在接受HAART治疗的儿童和青少年中检测到82%的HIV特异性CTL应答（无法检测的病毒载量+ HIV病毒血症）。在HAART长期病毒抑制的儿童HIV患者中也检测到自身中和抗体（ANAB）反应。这项拟议的职业发展计划将包括以Yvonne布赖森和Otto Yang为导师的密切指导的患者导向研究，临床人群的结构化实验室评估沿着UCLA K30转化研究计划的教学课程。目的：我们提出了一个前瞻性分析的保护性免疫相关性和病毒遏制在两个良好的特点队列的儿童艾滋病患者接受HAART治疗。我们假设儿童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特异性细胞免疫应答（CDS-CTL和CD 4辅助）、ANAB应答和病毒多样性，并将通过HAART的启动而改变。受试者：队列I是一组接受HAART治疗的慢性HIV-1感染儿童/青少年。队列II是一组新诊断的围产期HIV-1感染婴儿，前瞻性随机分为早期或延迟HAART，随访5年以上。HIV特异性细胞和体液免疫应答可能根据队列I中HAART病毒学应答的水平和持久性而变化。早期HAART治疗可能会抑制病毒复制，影响病毒多样性，并保护队列II中的免疫系统。HIV细胞和体液免疫应答可能在早期与延迟治疗组之间以及根据疾病进展而变化。

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.