title: Long-term effects of protease-inhibitor-based combination therapy on CD4 T-cell recovery in HIV-1-infected children and adolescents.
abstract: BACKGROUND
  There is limited evidence about longer-term effects of combination antiretroviral therapy that includes protease inhibitors (PIs) on the immunological status of HIV-1-infected children. Better understanding might help to resolve questions on when to initiate treatment.
  
  
  METHODS
  The change in percentage of CD4-positive T lymphocytes (CD4%) was investigated in 1012 previously treated HIV-1-infected children (aged 0-17 years) who were enrolled in research clinics in the USA before 1996 and followed up to 2000. 702 started PI-based combination therapy. Data analyses ignored subsequent treatment changes.
  
  
  RESULTS
  Among the 1012 children, the median CD4% increased from 22% to 28% between 1996, when PIs were first prescribed, and 2000. For the 702 who started PI-based therapy, the mean CD4% increase after 3 years was largest among participants with the greatest immunosuppression (15.7%, 10.6%, 5.1%, and 2.0% for participants with CD4% before therapy of <5%, 5-14%, 15-24%, and >25%; p<0.0001). After adjustment for pre-PI CD4%, the mean increase was largest among the youngest participants (9.2%, 8.0%, and 4.3% for ages <5 years, 5-9 years, and >10 years; p=0.001). However, only a minority of significantly immunocompromised participants (33%, 26%, and 49% of those with pre-PI CD4% of <5%, 5-14%, or 15-24%) achieved CD4% values above 25%, whereas 84% of those with pre-PI values above 25% maintained such values.
  
  
  CONCLUSIONS
  Although PI-based therapy was associated with substantial improvements in CD4%, initiation before severe immunosuppression and at younger ages may be more effective for recovery or maintenance of normal CD4%. Randomised investigation of when to start combination therapy in children, particularly infants, is needed.
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, MA, Boston 02115, USA
authors.forename: Chang-Heok
authors.initials: CH
authors.lastname: Soh
authors.forename: James M
authors.initials: JM
authors.lastname: Oleske
authors.forename: Michael T
authors.initials: MT
authors.lastname: Brady
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Spector
authors.forename: William
authors.initials: W
authors.lastname: Borkowsky
authors.forename: Sandra K
authors.initials: SK
authors.lastname: Burchett
authors.forename: Marc D
authors.initials: MD
authors.lastname: Foca
authors.forename: Edward
authors.initials: E
authors.lastname: Handelsman
authors.forename: Eleanor
authors.initials: E
authors.lastname: Jiménez
authors.forename: Wayne M
authors.initials: WM
authors.lastname: Dankner
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
mesh_terms: D000293:Adolescent; D000367:Age Factors; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D017320:HIV Protease Inhibitors