ACTG 219

行动219

• 批准号: 7378758
• 负责人: NANCY HUTTON
• 金额: $ 7.22万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7378758
• 关键词: ACTG; 219

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. The issue of long-term benefits and/or adverse effects related to specific treatments can be addressed best by defined data collection to ensure that key survival, growth, development, and clinical and laboratory information is collected longitudinally in an individual patient database (IPD). This protocol provides a mechanism to systematically track late outcomes among children enrolled in PACTG perinatal, primary therapy, and Opportunistic Infection (OI) prophylaxis treatment protocols. This includes perinatally HIV-exposed and newly diagnosed infants with emphasis on perinatally infected infants who are followed at PACTG sites. It also provides an effective over view of on how PACTG protocols are performing with regard to treatment, survival, and quality of life for children infected with HIV. It is anticipated that the longitudinal data gathered in this protocol will enable investigators in the PACTG to answer a variety of other long-term research questions and hypotheses specific to treatment-related protocols. For example, growth and development (with Tanner staging) are parameters unique to pediatric and adolescent medicine, where HIV viral/host interactions in growth and pubertal development are critical outcome measures. The Adherence Working Group of the Supportive Care/Quality of Life Committee in the Complications of HIV Infection Research Advisory Committee (RAC) has developed an adherence module that is included in PACTG 219C, Version 3.0. The ability of families and children to adhere to multiple drug regimens that have been demonstrated to be safe and effective in the clinical trials context must be extended and evaluated as the children continue on combination therapy during their long term clinical care (7-11). Rationale for Version 3.0 Since the development of PACTG 219C, Version 1.0, in 1993 and an update in 1995 (Version 2.0), there have been dramatic developments in the understanding of the pathogenesis of HIV infection. The developments include major advances in the early diagnosis of the infection status of the perinatally exposed newborn (HIV-1 DNA PCR), virological monitoring of infection (HIV-1 RNA PCR), and quantitative and qualitative immune evaluation. In addition, there have been major advances in our ability to prevent perinatal HIV transmission, as well as to treat HIV infection in children using aggressive combinations of antiretroviral drugs. Immune based therapies, better prevention and treatment of opportunistic infections, and improved supportive care/quality of life, have all contributed to making pediatric HIV infection a chronic rather than rapidly fatal disease. Based on these advances, the PACTG 219C protocol team was reformed and expanded by the PEC to develop Version 3.0. Four ad hoc working groups (Perinatal Transmission, Primary Therapy, Complications of HIV Infection, and Supportive Care/Quality of Life/Long-Term Survivors) were established and given the charge to redefine, update, and expand the objectives and hypotheses of PACTG 219C. These working groups, with representation and input from the Statistical and Data Analysis Center (SDAC), as well as the Adolescent, Immunology, and Virology Scientific Committees, have identified objectives (long-term follow-up, natural history questions) and specific, testable hypotheses for Version 3.0 of PACTG 219C. (The supportive Care/Quality of Life/Long-Term Survivor hypotheses have been included under the Complications of HIV section.) Version 3.0 of PACTG 219C provides a longitudinal 'backbone' protocol appropriate for the follow-up of long-term outcomes in infants, children, and adolescents prospectively followed at PACTG sites while remaining cost effective. The ability of PACTG 219C to meet these goals is made possible by: (1) improved electronic transfer of data from other PACTG protocols into the PACTG 219C data base, (2) simplified data collection forms (CRFs), (3) the improved reliability of clinically obtained viral load and CD4 levels, and (4) the increase in the number of clinical visits and repository cell/plasma specimens. This protocol also emphasizes the gathering of longitudinal clinical, treatment, virologic, and immunologic data in an individual patient database (IPD). The IPD will track individual clinical courses, viral load, and immune profile over time, and will allow for cross-protocol analyses of treatment effects such as the impact of sustained suppression in viral

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。与特定治疗相关的长期益处和/或不良反应的问题最好通过明确的数据收集来解决，以确保关键的生存、生长、发育以及临床和实验室信息在个人患者数据库(IPD)中纵向收集。该方案提供了一种机制，系统地跟踪参加PACTG围产期、初级治疗和机会性感染(OI)预防治疗方案的儿童的晚期结局。这包括围产期接触艾滋病毒的婴儿和新诊断的婴儿，重点是围产期感染的婴儿，并在PACTG地点进行跟踪。它还提供了关于PACTG方案在感染艾滋病毒儿童的治疗、生存和生活质量方面执行情况的有效概述。预计在该方案中收集的纵向数据将使PACTG的研究人员能够回答针对治疗相关方案的各种其他长期研究问题和假说。例如，生长和发育(包括Tanner分期)是儿科和青少年医学特有的参数，其中艾滋病毒病毒/宿主在生长和青春期发育中的相互作用是关键的结果衡量标准。支持护理/生活质量委员会在艾滋病毒感染并发症研究咨询委员会(RAC)的坚持工作组开发了一个遵守模块，该模块包括在PACTG 219C，3.0版中。家庭和儿童坚持在临床试验中被证明是安全有效的多种药物方案的能力必须随着儿童在其长期临床护理期间继续接受联合治疗而得到扩展和评估(7-11)。3.0版的基本原理自1993年开发PACTG 219C 1.0版和1995年更新(2.0版)以来，对艾滋病毒感染的发病机制的理解有了巨大的发展。这些进展包括围产期暴露新生儿感染状况的早期诊断(艾滋病毒-1 DNA聚合酶链式反应)、感染的病毒学监测(艾滋病毒-1核糖核酸聚合酶链式反应)以及定量和定性免疫评估方面的重大进展。此外，我们在预防围产期艾滋病毒传播以及使用积极的抗逆转录病毒药物组合治疗儿童艾滋病毒感染方面取得了重大进展。以免疫为基础的治疗、更好地预防和治疗机会性感染以及改善支持性护理/生活质量，所有这些都有助于使儿童艾滋病毒感染成为一种慢性疾病，而不是迅速致命的疾病。在这些进展的基础上，PEC对PACTG 219C协议团队进行了改革和扩展，以开发3.0版。成立了四个特设工作组(围产期传播、初级治疗、艾滋病毒感染并发症和支持性护理/生活质量/长期幸存者)，负责重新定义、更新和扩展PACTG 219C的目标和假设。这些工作组在统计和数据分析中心(SDAC)以及青少年、免疫学和病毒学科学委员会的代表和投入下，确定了PACTG 219C版本3.0的目标(长期跟踪、自然史问题)和具体的、可检验的假设。(支持性护理/生活质量/长期生存者假设已包括在艾滋病毒并发症部分。)PACTG 219C版本3.0提供了一种纵向“主干”方案，适用于对在PACTG站点进行前瞻性跟踪的婴儿、儿童和青少年的长期结果进行跟踪，同时保持成本效益。PACTG 219C之所以能够实现这些目标，是因为：(1)改进了从其他PACTG协议到PACTG 219C数据库的数据电子传输，(2)简化了数据收集表格(CRF)，(3)提高了临床获得的病毒载量和CD4水平的可靠性，以及(4)临床就诊次数和存储细胞/血浆样本的增加。该方案还强调在个人患者数据库(IPD)中收集纵向的临床、治疗、病毒学和免疫学数据。IPD将随着时间的推移跟踪个人的临床病程、病毒载量和免疫状况，并将允许对治疗效果进行跨方案分析，例如持续抑制病毒的影响。