title: Using CD4 percentage and age to optimize pediatric antiretroviral therapy initiation.
abstract: BACKGROUND
  Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation.
  
  
  METHODS
  HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization "mild" immunosuppression and CD4% <10th percentile, were analyzed for improvement to a normal CD4% (≥10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years.
  
  
  RESULTS
  Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with "severe" immunosuppression, more children with "mild" immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or "advanced" immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in >90% recovery when initiating HAART with "mild" immunosuppression at any age or "advanced" immunosuppression at age <3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%).
  
  
  CONCLUSIONS
  Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks.
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina; Department of Epidemiology, Gillings School of Global Public Health, Division of Infectious Diseases, Department of Pediatrics, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City, Kansas City, Missouri; deyin@cmh.edu.
authors.forename: Dwight E
authors.initials: DE
authors.lastname: Yin
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts;
authors.forename: Meredith G
authors.initials: MG
authors.lastname: Warshaw
authors.affiliation: Department of Epidemiology, Gillings School of Global Public Health, Division Infectious Diseases, Department of Medicine, School of Medicine, and.
authors.forename: William C
authors.initials: WC
authors.lastname: Miller
authors.affiliation: Infections Group, Medical Research Council Clinical Trials Unit.
authors.forename: Hannah
authors.initials: H
authors.lastname: Castro
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina;
authors.forename: Susan A
authors.initials: SA
authors.lastname: Fiscus
authors.affiliation: Infections Group, Medical Research Council Clinical Trials Unit.
authors.forename: Lynda M
authors.initials: LM
authors.lastname: Harper
authors.affiliation: Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts;
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Harrison
authors.affiliation: Infectious Diseases and Microbiology Unit, Institute of Child Health, and.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Klein
authors.affiliation: Institute of Child Health and CoMPLEX, University College London, London, United Kingdom;
authors.forename: Joanna
authors.initials: J
authors.lastname: Lewis
authors.affiliation: Division of Pediatric Infectious Disease, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington; and.
authors.forename: Ann J
authors.initials: AJ
authors.lastname: Melvin
authors.affiliation: Section of Pediatrics, Imperial College London, London, United Kingdom.
authors.forename: Gareth
authors.initials: G
authors.lastname: Tudor-Williams
authors.affiliation: Division of Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina;
authors.forename: Ross E
authors.initials: RE
authors.lastname: McKinney
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000592:standards*; D018791:CD4 Lymphocyte Count / Q000379:methods; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male
chemical_list: D019380:Anti-HIV Agents
keywords: HIV; child; immunologic; reconstitution; treatment failure