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

J Pediatr. 1998 Oct;133(4):500-8. doi: 10.1016/s0022-3476(98)70057-5.


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.

Study design: 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Anti-HIV Agents / therapeutic use*
  • CD4 Antigens / immunology
  • Child
  • Child, Preschool
  • Didanosine / therapeutic use*
  • Disease Progression
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • HIV Infections / complications
  • HIV Infections / drug therapy*
  • HIV Infections / mortality
  • HIV-1*
  • Humans
  • Lamivudine / therapeutic use*
  • Male
  • Neurodegenerative Diseases / etiology
  • Polymerase Chain Reaction / methods
  • RNA, Viral / immunology
  • Survival Rate
  • Zidovudine / therapeutic use*


  • Anti-HIV Agents
  • CD4 Antigens
  • RNA, Viral
  • Lamivudine
  • Zidovudine
  • Didanosine