Prospective Study-Viral/Immune Correlates Pediatric HIV

简介(由申请人提供)：程雅琪是加州大学洛杉矶分校儿科传染病专家和临床讲师，儿科学助理教授。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员，专门研究儿科HIV-1感染。这位候选人在团契期间开始对接受高效抗逆转录病毒治疗(HAART)的儿童艾滋病毒患者的免疫重建感兴趣。她发起了一项对细胞和体液免疫反应的前瞻性评估，以应对召回抗原(破伤风助剂/甲型肝炎)。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)肽图技术来扩大该项目，以评估拟议研究人群中的横截面患者。她在HAART(无法检测到的病毒载量+HIV病毒血症)的儿童和青少年中检测到82%的HIV特异性CTL反应。在HAART病毒抑制时间延长的儿童HIV患者中也检测到自体中和抗体(ANAB)反应。这项拟议的职业发展计划将包括由Yvonne Bryson和Otto Yang担任导师的密切指导的以患者为导向的研究，对临床人群进行结构化的实验室评估，以及加州大学洛杉矶分校K30翻译研究计划的教学课程。目的：我们对接受HAART治疗的两个特征良好的儿童HIV患者的保护性免疫相关因素和病毒遏制进行了前瞻性分析。我们假设，儿童HIV疾病进展的差异与宿主免疫压力的差异直接相关，包括HIV特异性细胞免疫反应(CDS CTL和CD4 Help)、ANAB反应和病毒多样性，并将通过HAART的启动而改变。研究对象：队列I是接受HAART治疗的一组慢性HIV-1感染的儿童/青少年。队列II是一组新诊断的围产期感染HIV-1的婴儿，前瞻性地随机接受早期或延迟的HAART，随访超过5年。HIV特异的细胞和体液免疫反应可能会因HAART在队列I中的病毒学反应的水平和持久性而有所不同。在队列II中，早期使用HAART可能包含病毒复制、影响病毒多样性并保护免疫系统。HIV细胞和体液免疫反应在早期和延迟治疗组之间以及疾病进展情况下可能有所不同。

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.