title: A randomized study of combined zidovudine-lamivudine versus didanosine monotherapy in children with symptomatic therapy-naive HIV-1 infection. The Pediatric AIDS Clinical Trials Group Protocol 300 Study Team.
abstract: OBJECTIVE
  The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 300 assessed the clinical efficacy and safety of combination zidovudine/lamivudine (ZDV/3TC) compared with either didanosine (ddI) alone or combination ZDV/ddI.
  
  
  METHODS
  Children with symptomatic human immunodeficiency virus (HIV) infection, 6 weeks through 15 years of age, were stratified according to age and randomly assigned to receive ddI, ZDV/3TC, or ZDV/ddI. The primary endpoint was time to first progression of HIV disease or death. Enrollment in the ZDV/ddI arm stopped after 11 months on the basis of results of PACTG Protocol 152, but blinded follow-up continued.
  
  
  RESULTS
  For the 471 children who could be evaluated, the median age was 2.7 years, median CD4 cell count was 699 cells/mm3, and median log10 HIV RNA was 5.1/mL. Median follow-up was 9.4 months. Patients receiving ZDV/3TC had a lower risk of HIV disease progression or death than those receiving ddI alone (15 vs 38 failures, P = .0006) and a lower risk of death (3 vs 15 deaths, P = .0039). Weight and height growth rates, CD4+ cell counts, and RNA concentrations showed results favoring ZDV/3TC. For patients concurrently randomized to all 3 treatment arms, both ZDV/3TC and ZDV/ddI recipients had lower risk of HIV disease progression than those who received ddI alone (P = .0026 and P = .0045).
  
  
  CONCLUSIONS
  Combination therapy with either ZDV/3TC or ZDV/ddI was superior, as determined by clinical and laboratory measures, to monotherapy with ddI.
authors.affiliation: Department of Pediatrics and Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: McKinney
authors.forename: G M
authors.initials: GM
authors.lastname: Johnson
authors.forename: K
authors.initials: K
authors.lastname: Stanley
authors.forename: F H
authors.initials: FH
authors.lastname: Yong
authors.forename: A
authors.initials: A
authors.lastname: Keller
authors.forename: K J
authors.initials: KJ
authors.lastname: O'Donnell
authors.forename: P
authors.initials: P
authors.lastname: Brouwers
authors.forename: W G
authors.initials: WG
authors.lastname: Mitchell
authors.forename: R
authors.initials: R
authors.lastname: Yogev
authors.forename: D W
authors.initials: DW
authors.lastname: Wara
authors.forename: A
authors.initials: A
authors.lastname: Wiznia
authors.forename: L
authors.initials: L
authors.lastname: Mofenson
authors.forename: J
authors.initials: J
authors.lastname: McNamara
authors.forename: S A
authors.initials: SA
authors.lastname: Spector
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015704:CD4 Antigens / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D016049:Didanosine / Q000627:therapeutic use*; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D019636:Neurodegenerative Diseases / Q000209:etiology; D016133:Polymerase Chain Reaction / Q000379:methods; D012367:RNA, Viral / Q000276:immunology; D015996:Survival Rate; D015215:Zidovudine / Q000627:therapeutic use*
chemical_list: D019380:Anti-HIV Agents; D015704:CD4 Antigens; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D016049:Didanosine