title: Reliability of CD4 quantitation in human immunodeficiency virus-positive children: implications for definition of immunologic response to highly active antiretroviral therapy.
abstract: Our objective was to develop data-based algorithms for definition of immunologic response to AIDS therapies in pediatric patients, taking account of T-cell subset measurement errors. The study design involved cross-protocol analysis of 2,148 enrollees in six completed Pediatric AIDS Clinical Trials Group trials. We used standard quantitation of T-cell subsets; linear modeling with mean-dependent measurement error variance was used to develop 95% tolerance limits for change in CD4%. For individuals with a CD4% of approximately 25%, the measurement error-based 95% tolerance interval ranges from 15% to 35%, whereas for individuals with a CD4% of approximately 5%, the tolerance interval ranges from 3% to 7%. When pairs of CD4% measures taken within a time interval of less than 30 days are averaged to estimate steady-state CD4%, tolerance interval width decreases by approximately 30%. A simple graphical tool that provides a data-based criterion for immunologic response over and above variation ascribable to T-cell measurement error is provided. Variability in CD4% due to measurement error is substantial, increases with level of CD4%, and complicates assessment of immunologic response to therapy. Replicates of CD4% measures could be used to improve precision of interpretation of CD4% measures.
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard University School of Public Health, Channing Laboratory, Brigham and Women's Hospital, 181 Longwood Ave., Boston, Massachusetts 02115, USA. stvjc@channing.harvard.edu
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
mesh_terms: D000465:Algorithms; D023241:Antiretroviral Therapy, Highly Active; D018791:CD4 Lymphocyte Count; D002648:Child; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000187:drug effects; D015233:Models, Statistical; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012189:Retrospective Studies