TRIAL OF THE SAFETY AND IMMUNOGENICITY OF FLUMIST IN HIV-INFECTED CHILDREN

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。本研究将评价FluMist TM疫苗在HIV感染儿童中的安全性、免疫原性和疫苗病毒脱落。其次，本研究将检查安全性、免疫原性和病毒脱落如何随接种时和既往免疫抑制时的免疫状态而变化。目前的护理标准是用IAIV（Fluzone R）对艾滋病毒感染儿童进行免疫接种。为了检查FluMist TM的安全性和/或免疫原性是否与Fluzone R显著不同，研究将包含两个组，A组（n=150）接受FluMist TM，B组（n=150）接受Fluzone R。鉴于FluMist TM与Fluzone R在总体安全性和严重不良事件发生率方面预计相似，因此该研究对FluMist TM与Fluzone R进行比较的统计功效有限。对于FluMist TM与Fluzone R的比较，当疫苗效应无显著分层时，将跨分层汇总数据。然而，由于疫苗效应可能会因分层而异，因此提供了分层计算以及汇总分析。对于毒性和免疫原性，A组和B组缓解率差异的置信区间将通过精确方法单独估计。本研究将招募300例受试者。受试者将根据免疫状态分为3个分层。每组将包含100名受试者，随机分配，其中50名接受FluMist TM，另50名接受Fluzone R。由于流感疫苗的性质每年都在变化，所有受试者都需要在PACTG研究中心研究开始招募至最后一次接种日期（2004年11月19日）之间入组。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This study will evaluate the safety, immunogenicity, and shedding of vaccine virus in HIV-infected children immunized with FluMist TM. Secondarily, the study will examine how safety, immunogenity, and viral shedding vary as a function of immune status at the time of vaccination and with prior immune suppression. The current standard of care is to immunize HIV-infected children with IAIV (Fluzone R). In order to examine whether the safety and/or immunogenicity of FluMist TM differs significantly from that of Fluzone R the study will contain two arms, with Arm A (n=150) receiving FluMist TM and Arm B (n=150) receiving Fluzone R. The study will have limited statistical power for FluMist TM versus Fluzone R comparisons, given that they are expected to be similar with respect to overall safety and the rate of serious adverse events. For FluMist TM versus Fluzone R comparisons, data will be pooled across strata when there are no significant strata by vaccine effects. However, since there is a possibility that vaccine effects will vary across strata, calculations are present for with strata, as well as pooled analyses. The confidence interval around the difference between the response rates of arms A and B will be estimated separately for toxicity and immunogenicity be exact methods. The study will accrue 300 subjects. Subjects will be stratified on the basis of immunologic status into 3 strata. Each Group will contain 100 subjects, randomized such that 50 recieve FluMist TM, while the other 50 receive Fluzone R. All subjects need to be enrolled between the time the study opens to accrual at PACTG sites and the last date of vaccination (November 19, 2004) because of the changing nature of the influenza vaccines from year to year.