A Prospective Study of Viral and Immune Correlates in Pediatric HIV-1 Infection

简介（由申请人提供）：Natascha Ching是加州大学洛杉矶分校的儿科传染病专家和临床讲师，儿科助理教授。候选人的职业目标是成为一名独立的以患者为导向的研究人员，专门研究儿科HIV-1感染。在研究期间，该候选人对儿科艾滋病患者接受高效抗逆转录病毒治疗（HAART）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（破伤风增强剂/甲型肝炎）。基于她的初步数据，她通过学习HIV细胞毒性T淋巴细胞（CTL）肽定位的新技术来扩展该项目，以评估拟议研究人群中的患者横截面。她在82%接受HAART治疗的儿童和青少年中检测到HIV特异性CTL反应（无法检测到病毒载量+ HIV病毒血症）。自体中和抗体（ANAB）反应也可在HAART治疗中病毒长期抑制的儿童HIV患者中检测到。这一职业发展计划将包括由Yvonne Bryson和Otto Yang作为导师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转化研究项目的教学课程。目的：我们对两组接受HAART治疗的儿童HIV患者的保护性免疫相关因子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变异性直接相关，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，并将因HAART的开始而改变。研究对象：队列1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，前瞻性随机分配到早期或延期HAART治疗，随访超过5年。在队列i中，HIV特异性细胞和体液免疫反应可能根据HAART的病毒学反应的水平和持久性而变化。在队列II中，早期使用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在早期和延迟治疗组之间以及疾病进展之间有所不同。

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.