ACTG 219

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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