Immunophenotypic analysis of HIV-infected children: Alterations within the first year of life, changes with disease progression, and longitudinal analyses of lymphocyte subsets

Perinatal infection with human immunodeficiency virus (HIV) results in tremendous activation of the pediatric immune system. An important component of understanding the pathogenesis of this disease is to characterize and quantify antigenic indicators of activation within the peripheral lymphocyte population. We measured T-lymphocyte activation and maturation antigens in a cohort of 112 HIV-infected children treated with antiretroviral therapy according to the current standard of care. Changes in expression of CD95, HLA-DR, and CD45RO were evident in 22 HIV-infected children younger than 1 year of age. A comparison of phenotypic profiles of children in mild, moderate, and severe immune categories revealed perturbations of CD28, CD38, CD45RA, CD45RO, CD95, and HLA-DR. Finally, a novel analysis of 56 HIV-infected children based on the repeated collection of data over time (median of seven observations over 33 months) demonstrated a strong negative correlation between the percentage CD4 and the percentage of CD45RO, CD95, and HLA-DR on both CD4 and CD8 cells. Our data implicate persistent immune activation, beginning within the first year of life, as a major driving force in the pathogenesis of perinatally acquired HIV disease.