PACTG 1047

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 儿科艾滋病临床试验小组(PACTG)1047是一项II期、双盲、安慰剂对照研究，研究四价人乳头瘤病毒(QHPV)疫苗在7岁至12岁以下感染人类免疫缺陷病毒(HIV)-1的男孩和女孩人群中的安全性和免疫原性。这种疫苗也被称为Gardasil，由默克实验室开发，目标病毒类型为6、11、16和18。在感染艾滋病毒和未感染的女性中，最常见的致癌性人乳头瘤病毒(HPV)类型是HPV 16和18。最常见的HPV类型是6和11。2006年5月18日，联邦药品管理局(FDA)的一个咨询委员会审查了默克公司申请Gardasil许可的申请。预计该疫苗将于2006年6月初获得批准。然而，在任何临床试验中，没有艾滋病毒感染儿童或具有其他免疫损害条件的儿童登记或接种单价或四价HPV疫苗。 感染艾滋病毒的妇女的宫颈癌发病率增加，因为免疫能力随着艾滋病毒疾病的进展而下降。与未感染艾滋病毒的妇女相比，感染艾滋病毒的妇女的宫颈癌范围更广，更难治愈，标准临床护理后的复发率更高。此外，艾滋病毒感染者罹患阴茎和肛门癌的风险增加，包括没有报告有过肛交经历的人。由于HPV是一种性传播感染，女性的预防也将通过其伴侣的预防来加强。因此，评估一种预防性疫苗是一项重要的科学目标，它可以保护感染艾滋病毒的女孩和男孩免受最常见的HPV感染，这些类型会导致肛门生殖发育不良和外生殖器损伤。 研究人群将包括从美国PACTG多个地点招募的120名感染HIV-1的儿童。该方案将在7岁至12岁的儿童中实施，因为这种预防性疫苗很可能会在儿童性行为活跃之前使用。预计在安全性方面，qHPV疫苗在这个年龄段的艾滋病毒感染儿童中将普遍耐受性良好。受试者将被随机选择接受研究疫苗或安慰剂，在研究的第一阶段，75%的人接受活性疫苗，25%的人接受安慰剂。由于预计免疫状况较弱的儿童与免疫系统较强的儿童的反应不同，因此将根据他们的CD4%病史和目前的CD4%将人群分为三组。 第一阶段：在满足资格标准(包括对月经女性进行实时怀孕测试)后，对疫苗/安慰剂进行3次肌肉注射(在入院时、第8周和第24周)。随后的安全性评估包括免疫后直接在诊所至少30分钟，第3天电话评估，第4、8、12、24和28周的研究访问。受试者还将被要求记录注射后的口腔温度和症状。(见附件IV，疫苗接种成绩单)如果出现任何异常或令人震惊的症状，将强烈鼓励受试者致电学习护士或Salazar医生。 第二阶段：在第96周，各组将被解盲。如果疫苗被认为是安全的和耐受性良好的，将给那些接种了活性qHPV的儿童接种第四剂。安慰剂组现在将开始积极的qHPV方案并进行随访。对于接受第四剂活性qHPV的组，安全性随访将在第97、100和108周进行。那些在96周开始活跃的qHPV患者将以同样的方式接受跟踪，直到第124周。(请参阅附录1I A及IB。)。在整个研究过程中，将通过血液和唾液样本使用ELISPOT(抗HPV CMI)、HPV抗体CLIA(竞争性Luminex免疫分析)以及Ig G和Ig A抗HPV检测来评估免疫原性。

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. Pediatric Aids Clinical Trials Group (PACTG) 1047 is a phase II, double blind, placebo controlled study of the safety and immunogenicity of Quadrivalant Human Papilloma virus (QHPV) vaccine in a population of Human Immunodeficiency Virus (HIV)-1 infected boys and girls aged 7 years to under 12 years. The vaccine, also known as Gardasilwas developed by Merck Labs with the target viral types being 6, 11, 16, and 18. The most common oncogenic Human Papillomavirus (HPV) types that cause cervical dysplasia and cancer, in both HIV-infected and uninfected women, are HPV 16 and 18. The most common types of HPV, causing genital warts, are types 6 and 11. On May 18, 2006, an advisory committee for the Federal Drug Administration (FDA) reviewed Merck's application for licensure of Gardasil¿. It is expected that the vaccine will receive approval in early June, 2006. However, no HIV-infected children, or children with other immune compromising conditions, have been enrolled or received monovalent or quadrivalent HPV vaccine in any clinical trials. The incidence of cervical cancer in HIV-infected women increases as immune competence decreases with progression of HIV disease. Cervical cancer is more extensive and more difficult to cure in HIV-infected women than in HIV-uninfected women and the recurrence rate after standard clinical care is higher. In addition, HIV-infected individuals are at increased risk for penile and anal cancer, including individuals who do not report prior anal intercourse. Because HPV is a sexually transmitted infection, prevention in women will be enhanced by prevention in their partners as well. Thus, evaluation of a prophylactic vaccine, which might protect HIV-infected girls and boys from infection with the most common HPV types that cause anogenital dysplasia and external genital lesions, is an important scientific goal. The study population will consist of 120 HIV-1 infected children recruited from multiple PACTG sites in the U.S. This protocol will be undertaken in children > 7 to < 12 years of age because it is likely that this preventative vaccine will be used before children become sexually active. It is expected that, in terms of safety, QHPV Vaccine will be generally well-tolerated in HIV-infected children in this age group. The subjects will be randomly selected to receive the study vaccine or placebo, with 75% receiving the active vaccine and 25% receiving placebo during Stage I of the study. Since it is expected that children with weaker immune status would respond differently from children with stronger immune systems, the population will be stratified into three groups based on their CD4% history and current CD4%. Stage I: After satisfying eligibility criteria including real-time pregnancy testing for menstruating females, the vaccine/placebo is given intramuscularly 3 times (at entry, week 8 and week 24). Subsequent safety assessment consists of at least 30 minutes in the clinic directly after immunization, a day 3 phone evaluation, study visits on week 4, 8, 12, 24, and 28. Subjects will also be asked to keep a record of oral temperature and symptoms following the injections. (See attached Appendix IV, the Vaccination Report Card) Subjects will be strongly encouraged to phone the study nurse or Dr. Salazar should any unusual or alarming symptoms occur. Stage II: At week 96, the groups will be unblinded. If the vaccine has been deemed safe and well tolerated, a fourth dose will be given to those children who had received active QHPV. The placebo group would now begin the regimen of active QHPV and follow up visits. For the group who receives the fourth dose of active QHPV, safety follow up will occur at weeks 97, 100 and 108. Those who begin active QHPV at 96 weeks will be followed in a likewise fashion until study week 124. (Please see attached Appendix 1I A and IB.) Throughout the course of the study, immunogenicity will be evaluated via blood and saliva samples using ELISPOT (anti-HPV CMI), HPV antibody cLIA (Competitive Luminex Immunoassay) and IgG and IgA anti-HPV testing.