PACTG 219

PACTG 219

• 批准号: 7604521
• 负责人: NANCY HUTTON
• 金额: $ 3.32万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7604521
• 关键词: Address; Adherence; Adolescent; Adolescent Medicine; Adverse effects; Advisory Committees; Anti-Retroviral Agents; Caring; Charge; Child; Childhood; Chronic; Clinical; Clinical Treatment; Clinical Trials; Combined Modality Therapy; Computer Retrieval of Information on Scientific Projects Database; DNA; Data; Data Collection; Databases; Development; Disease; Early Diagnosis; Electronics; Enrollment; Ensure; Evaluation; Family; Funding; Goals; Grant; Growth; Growth and Development function; HIV; HIV Infections; HIV-1; Immune; Immunologics; Immunology; Individual; Infant; Infection; Institution; Laboratories; Long-Term Survivors; Monitor; Natural History; Newborn Infant; Newly Diagnosed; Numbers; Opportunistic Infections; Outcome; Outcome Measure; Pathogenesis; Patients; Perinatal; Pharmaceutical Preparations; Plasma Cells; Polymerase Chain Reaction; Prevention and Treatment of Opportunistic Infection; Prophylactic treatment; Protocols documentation; Quality of life; RNA; Research; Research Personnel; Resources; Site; Source; Specimen; Staging; Statistical Data Interpretation; Supportive care; Time; Treatment Protocols; United States National Institutes of Health; Update; Vertebral column; Viral; Viral Load result; Visit; Work; base; cost effective; follow-up; improved; prevent; repository; transmission process; treatment effect; virology

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 load.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。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 研究中心，而研究中心不一定是研究者所在的机构。 与特定治疗相关的长期获益和/或不良反应问题最好通过定义的数据收集来解决，以确保在个体患者数据库（IPD）中纵向收集关键生存、生长、发育以及临床和实验室信息。 该方案提供了一种机制，系统地跟踪在PACTG围产期，主要治疗和肠道感染（OI）预防治疗方案中招募的儿童的晚期结局。 这包括围产期艾滋病毒暴露和新诊断的婴儿，重点是在PACTG站点随访的围产期感染婴儿。 它还提供了一个有效的关于PACTG协议是如何执行方面的治疗，生存和生活质量的儿童感染艾滋病毒。 预计本方案中收集的纵向数据将使PACTG的研究者能够回答各种其他长期研究问题和治疗相关方案的特定假设。 例如，生长和发育（坦纳分期）是儿科和青少年医学特有的参数，其中生长和青春期发育中的HIV病毒/宿主相互作用是关键的结局指标。 HIV感染并发症研究咨询委员会（RAC）支持性治疗/生活质量委员会的依从性工作组开发了一个依从性模块，包含在PACTG 219 C，版本3.0中。 家庭和儿童坚持多种药物治疗方案的能力，已被证明是安全和有效的临床试验背景下，必须扩大和评估的儿童继续在其长期的临床护理（7-11）的联合治疗。 版本3.0的依据 自PACTG 219 C 1.0版于1993年开发并于1995年更新（2.0版）以来，对HIV感染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（HIV-1 DNA PCR）、感染的病毒学监测（HIV-1 RNA PCR）以及定量和定性免疫评价方面的重大进展。 此外，我们在预防围产期艾滋病毒传播以及使用抗逆转录病毒药物的积极组合治疗儿童艾滋病毒感染的能力方面取得了重大进展。 基于免疫的治疗、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，都有助于使儿科HIV感染成为慢性而不是快速致命的疾病。 基于这些进展，PEC对PACTG 219 C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、HIV感染并发症和支持性护理/生活质量/长期存活者），负责重新定义、更新和扩展PACTG 219 C的目标和假设。 这些工作组由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输入，已经确定了PACTG 219 C 3.0版的目标（长期随访、自然史问题）和具体的可检验假设。 (The支持性护理/生活质量/长期生存假设已纳入HIV并发症部分。） PACTG 219 C 3.0版提供了一种纵向“骨干”方案，适用于在PACTG研究中心前瞻性随访的婴儿、儿童和青少年的长期结局随访，同时保持成本效益。 PACTG 219 C实现这些目标的能力是通过以下方式实现的：（1）改进从其他PACTG方案到PACTG 219 C数据库的数据电子传输，（2）简化数据采集表（CRF），（3）提高临床获得的病毒载量和CD 4水平的可靠性，以及（4）增加临床访视和储存细胞/血浆标本的数量。 该方案还强调在个体患者数据库（IPD）中收集纵向临床、治疗、病毒学和免疫学数据。 IPD将随时间跟踪个体临床病程、病毒载量和免疫特征，并允许对治疗效果进行跨方案分析，例如持续抑制病毒载量的影响。