A randomized study of combined zidovudine-lamivudine versus didanosine monotherapy in children with symptomatic therapy-naive HIV-1 infection

• Published in: The Journal of pediatrics 1998-10, Vol.133 (4), p.500-508
• Main Authors: McKinney, Ross E., Johnson, George M., Stanley, Kenneth, Yong, Florence H., Keller, Amy, O’Donnell, Karen J., Brouwers, Pim, Mitchell, Wendy G., Yogev, Ram, Wara, Diane W., Wiznia, Andrew, Mofenson, Lynne, McNamara, James, Spector, Stephen A.
• Format: Article
• Language: English
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Medical sciences; Pharmacology. Drug treatments
• ISSN: 0022-3476; 1097-6833
• 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/mm 3, and median log 10 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. (J Pediatr 1998;133:500-8)