Predictors of immunologic long-term nonprogression in HIV-infected children: Implications for initiating therapy

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.