title: Immunoreconstitution after ritonavir therapy in children with human immunodeficiency virus infection involves multiple lymphocyte lineages.
abstract: OBJECTIVE
  To evaluate lymphocyte reconstitution after protease inhibitor therapy in children with human immunodeficiency virus (HIV) infection.
  
  
  METHODS
  Forty-four HIV-infected children receiving ritonavir monotherapy followed by the addition of zidovudine and didanosine were evaluated during a phase I/II clinical trial. The cohort had a median age of 6.8 years and advanced disease (57% Centers for Disease Control and Prevention stage C, 73% immune stage 3) and was naive to protease inhibitor therapy.
  
  
  RESULTS
  After 4 weeks of therapy, there was a significant increase in CD4(+) and CD8(+) T cells. CD4(+) T cells continued to increase, whereas CD8(+) T cells returned to baseline by 24 weeks. Unexpectedly, there was a significant increase in B cells. Changes in CD4(+) T-cell subsets revealed an initial increase in CD4(+) CD45RO T cells followed by a sustained increase in CD4(+) CD45RA T cells. Children <6 years of age had the highest increase in all lymphocyte populations. Significant improvement in CD4(+) T-cell counts was observed even in those children whose viral burden returned to pre-therapy levels.
  
  
  CONCLUSIONS
  Early increases in lymphocytes after ritonavir therapy are a result of recirculation, as shown by increases in B cells and CD4(+) CD45RO and CD8(+) T cells. Children exhibited a high potential to reconstitute CD4(+) CD45RA T cells even with advanced disease and incomplete viral suppression.
authors.affiliation: Department of Pediatrics and Department of Pathology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Sleasman
authors.forename: R P
authors.initials: RP
authors.lastname: Nelson
authors.forename: M M
authors.initials: MM
authors.lastname: Goodenow
authors.forename: D
authors.initials: D
authors.lastname: Wilfret
authors.forename: A
authors.initials: A
authors.lastname: Hutson
authors.forename: M
authors.initials: M
authors.lastname: Baseler
authors.forename: J
authors.initials: J
authors.lastname: Zuckerman
authors.forename: P A
authors.initials: PA
authors.lastname: Pizzo
authors.forename: B U
authors.initials: BU
authors.lastname: Mueller
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes; D018414:CD8-Positive T-Lymphocytes; D002648:Child; D002675:Child, Preschool; D016049:Didanosine / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D017493:Leukocyte Common Antigens; D016131:Lymphocyte Subsets; D019438:Ritonavir / Q000627:therapeutic use*; D019562:Viral Load; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D015215:Zidovudine; D017493:Leukocyte Common Antigens; D016049:Didanosine; D019438:Ritonavir