title: CD4(+) T-cell immunodeficiency is more dependent on immune activation than viral load in HIV-infected children on highly active antiretroviral therapy.
abstract: OBJECTIVE
  The aim of this study was to analyze the association between CD4(+) depletion and immune activation in HIV-1-infected children on highly active antiretroviral therapy (HAART).
  
  
  METHODS
  We carried out a cross-sectional study to determine the profile of several immunologic parameters in 143 children on HAART for more than 24 weeks. Children were stratified according to current immunologic status (CD4 < or =15%, 15%-25%, and > or =25%) and viral load (VL) levels (<400 copies/mL; 400-10,000 copies/mL; and >10,000 copies/mL). We also studied 23 uninfected children as healthy controls.
  
  
  METHODS
  Viral load (HIV-RNA copies per milliliter) was quantified using reverse transcriptase polymerase chain reaction molecular assay. T-cell subsets were determined by multiparametric flow cytometry.
  
  
  RESULTS
  HIV-infected children with low percentage of CD4(+) had high memory (CD45RO(+)) and low naive (CD45RA(+)) CD4(+) and CD8(+) T-cell values. Furthermore, children with CD4(+) >25% had similar memory and naive CD4(+) values as the healthy control group, whereas memory and naive CD8(+) subsets were different from the healthy control values. In these HIV-infected children, when CD4(+) was depleted, the amount of naive plus central memory CD8(+) (CD28(+)CD57(-)) cells was decreased, whereas effector CD8(+) (CD28(-)CD57(+)) cells were upregulated, and these values were always higher than healthy control values. Furthermore, children with low percentage of CD4(+) showed significant upregulation of HLA-DR(+)CD38(+) and HLA-DR(+) in both CD4(+) and CD8(+) T-cells independent of VL levels.
  
  
  CONCLUSIONS
  Our data suggest that elevated immune activation could be responsible for CD4(+) depletion rather than HIV replication because immunologic status is associated directly to immune activation and not to VL levels in HIV-infected children on HAART.
authors.affiliation: Laboratorio de Inmuno-Biología Molecular, Hospital Universitario "Virgen de Rocío," Sevilla, Spain. sresino.hgugm@salud.madrid.org
authors.forename: Salvador
authors.initials: S
authors.lastname: Resino
authors.forename: Elena
authors.initials: E
authors.lastname: Seoane
authors.forename: Maria Dolores Gurbindo
authors.initials: MD
authors.lastname: Gutiérrez
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: León
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Muñoz-Fernández
mesh_terms: D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002648:Child; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D008297:Male; D016176:T-Lymphocyte Subsets; D019562:Viral Load