Predictors of immunologic long-term nonprogression in HIV-infected children: Implications for initiating therapy - 18/08/11
, Charlotte Mao, MD b, Manhattan Charurat, PhD c, Leslie Serchuck, MD d, Marc Foca, MD e, Karen Hayani, MD f, Edward L. Handelsman, MD g, Clemente Diaz, MD h, Kenneth McIntosh, MD b, William T. Shearer, MD, PhD afor the Women and Infants Transmission Study
Reprint requests: Mary E. Paul, MD, Texas Children's Hospital, 6621 Fannin St F.C. 330.01, Houston, TX 77030.Houston, Tex, Boston, Mass, Baltimore and Bethesda, Md, New York and Brooklyn, NY, Chicago, Ill, and San Juan, Puerto Rico
Abstract |
Background |
Early markers that predict immunologic long-term nonprogression in infants with perinatally acquired HIV infection might assist in subsequent antiretroviral treatment decisions.
Objectives |
We sought to identify early markers of immunologic long-term HIV disease nonprogression.
Methods |
We analyzed immunologic and virologic characteristics at 1 and 2 months of age in HIV-infected children who were enrolled in the Women and Infants Transmission Study and born before 1995, comparing immunologic long-term nonprogressors (ILTNPs; n=10) with non-ILTNPs (n=127). ILTNPs were children who survived to 8 years or older with CD4 percentages of 25% or greater and counts of 500 cells/mm3 or more without receiving highly active antiretroviral therapy. Non-ILTNPs were defined as all other HIV-infected children. Receiver operating characteristic curve analysis was used to assess combined sensitivity and specificity for each of these characteristics and to determine potential threshold values to discriminate between ILTNPs and non-ILTNPs.
Results |
Characteristics in the first 2 months of life associated with ILTNP status in univariate analysis included higher CD4 percentages, lower CD8+ percentages, lower CD8+HLA-DR+ percentages, and lower HIV-1 RNA PCR values. In receiver operating characteristic analysis CD8+HLA-DR+ percentage had the best combined sensitivity and specificity for discriminating between ILTNPs and non-ILTNPs. CD8+HLA-DR+ percentages of 5% or less predicted ILTNP status with 80% sensitivity and 80% specificity. In multivariate analysis CD8+HLA-DR+ percentage of 5% or less remained a significant predictor of ILTNP status after adjusting for CD3+CD4+ percentage and HIV-1 RNA PCR value (odds ratio, 15.4; 95% CI, 1.9-124.7).
Conclusion |
CD8+ HLA-DR+ T-lymphocyte percentage of less than 5% at 1 to 2 months of age might be predictive for ILTNP status but should not be used at this time to make treatment-deferral decisions. Immune activation in HIV-infected infants might herald more disease progression. Further study of the use of this subpopulation in early infancy to predict ILTNP status is warranted.
Le texte complet de cet article est disponible en PDF.Key words : Human immunodeficiency virus, perinatal, immunologic long-term nonprogression, CD8+ T lymphocyte
Abbreviations used : Az, HAART, ILTNP, LTNP, OR, PCP, QA, ROC, WITS
Plan
| Principal investigators, study coordinators, program officers, and funding include the following: Clemente Diaz, Edna Pacheco-Acosta (University of Puerto Rico, San Juan, Puerto Rico; U01 AI 34858); Ruth Tuomala, Ellen Cooper, and Donna Mesthene (Boston/Worcester Site, Boston, Mass; 9U01 DA 15054); Phil LaRussa, Jane Pitt, and Alice Higgins (Columbia Presbyterian Hospital, New York, NY; U01 DA 15053); Sheldon Landesman, Edward Handelsman, and Gail Moroso (State University of New York, Brooklyn, NY; HD-3-6117); Kenneth Rich and Delmyra Turpin (University of Illinois at Chicago, Chicago, Ill; U01 AI 34841); William Shearer, Susan Pacheco, and Norma Cooper (Baylor College of Medicine, Houston, Tex; U01 HD 41983); Joana Rosario (National Institute of Allergy and Infectious Diseases, Bethesda, Md); Robert Nugent, (National Institute of Child Health and Human Development, Bethesda, Md); Vincent Smeriglio, Katherine Davenny (National Institute on Drug Abuse, Bethesda, Md); and Bruce Thompson (Clinical Trials and Surveys Corp, Baltimore, Md; N01 AI 85339). Scientific Leadership Core: Kenneth Rich, (PI), Delmyra Turpin (study coordinator; 1 U01 AI 50274-01). Additional support has been provided by local Clinical Research Centers as follows: Baylor College of Medicine, Houston, Tex (NIH GCRC RR00188) and Columbia University, New York, NY (NIH GCRC RR00645). |
Vol 115 - N° 4
P. 848-855 - avril 2005 Retour au numéro
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