title: Persistent subclinical immune defects in HIV-1-infected children treated with antiretroviral therapy.
abstract: OBJECTIVE
  With the introduction of combined antiretroviral therapy (cART), HIV-infected children can reach adulthood with minimal clinical complications. However, long-term HIV and cART in adults are associated with immunosenescence and end-organ damage. Long-term consequences of HIV and cART in children are currently unknown.
  
  
  METHODS
  We studied 69 HIV-infected children and adolescents under cART (0-23 years) for the occurrence of subclinical immunological aberrations in blood B and T cells, using detailed flow cytometric immunophenotyping and molecular analyses.
  
  
  RESULTS
  Children with undetectable plasma HIV viral loads for more than 1 year showed near-normal to normal CD4 T-cell numbers and near-normal numbers of most class-switched memory B cells. Furthermore, expansions of aberrant CD21 B cells contracted in patients with virus suppression. In contrast, CD8 effector T cells were increased, and CD4 memory T cells, Vγ9Vδ2 T cells and CD27IgA memory B cells were decreased and did not normalize under ART. Moreover, Vγ9Vδ2 T cells showed defects in their T-cell receptor repertoire selection.
  
  
  CONCLUSIONS
  Our results show the effectiveness of current cART to enable the build-up of phenotypically diverse B-cell and T-cell memory in HIV-infected children. However, several subclinical immune abnormalities were detected, which were partially caused by defective immune maturation. These persistent abnormalities were most severe in adolescents and therefore warrant long-term follow-up of HIV-infected children. Early identification of such immune defects might provide targets for monitoring future treatment optimization.
authors.affiliation: aDepartment of Immunology Erasmus MC, University Medical Center bDepartment of Pediatrics, Division of Infectious Diseases, Immunology and Rheumatology, Erasmus MC, University Medical Center-Sophia cDepartment of Viroscience, Erasmus MC, University Medical Center, Rotterdam, the Netherlands. *Present address: Department of Experimental Immunohematology, Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands. †Present address: Sint Franciscus Gasthuis, Rotterdam, the Netherlands.
authors.forename: Diana
authors.initials: D
authors.lastname: van den Heuvel
authors.forename: Gertjan J A
authors.initials: GJ
authors.lastname: Driessen
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Berkowska
authors.forename: Mirjam
authors.initials: M
authors.lastname: van der Burg
authors.forename: Anton W
authors.initials: AW
authors.lastname: Langerak
authors.forename: Dan
authors.initials: D
authors.lastname: Zhao
authors.forename: Halima
authors.initials: H
authors.lastname: Charif
authors.forename: Nico G
authors.initials: NG
authors.lastname: Hartwig
authors.forename: Annemarie M C
authors.initials: AM
authors.lastname: van Rossum
authors.forename: Pieter L A
authors.initials: PL
authors.lastname: Fraaij
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: Menno C
authors.initials: MC
authors.lastname: van Zelm
mesh_terms: D000293:Adolescent; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000188:drug therapy* / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D016131:Lymphocyte Subsets / Q000276:immunology*; D008297:Male; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents