500 both laboratory and clinical benefits in adult clinical trials. 2,3 Three-drug anti- retroviral regimens containing 2 nucleo- side analog reverse-transcriptase in- hibitors and a protease inhibitor are now recommended for initial treatment of children and adults with human immu- nodeficiency virus infection. 4,5 It is nev- ertheless important to identify nucleo- side regimens useful for initial therapy of Pediatric AIDS Clinical Trials Group Protocol 300 was designed to compare the clinical efficacy of combined zidovu- dine and lamivudine against the better of A A randomized study of combined zidovudine- lamivudine versus didanosine monotherapy in children with symptomatic therapy-naive HIV-1 infection Ross E. McKinney, Jr, MD, George M. Johnson, MD, Kenneth Stanley, PhD, Florence H. Yong, MS, Amy Keller, Karen J. O’Donnell, PhD, Pim Brouwers, PhD, Wendy G. Mitchell, MD, Ram Yogev, MD, Diane W. Wara, MD, Andrew Wiznia, MD, Lynne Mofenson, MD, James McNamara, MD, Stephen A. Spector, MD, and the Pediatric AIDS Clinical Trials Group Protocol 300 Study Team didanosine monotherapy or combination ZDV/ddI, as determined by PACTG 152. 1 Combination nucleoside antiviral regimens with 3TC have demonstrated From the Department of Pediatrics and Psychiatry, Duke University Medical Center, Durham, North Carolina; Department of Pediatrics, Medical University of South Carolina, Charleston; Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts; Glaxo Wellcome, Inc, Research Triangle Park, North Carolina; Intramural Research Pro- gram, National Cancer Institute, Bethesda, Maryland; Children’s Hospital of Los Angeles, Los Angeles, California; Depart- ment of Pediatrics, Children’s Memorial Hospital, Chicago, Illinois; Department of Pediatrics, University of California, San Francisco; Department of Pediatrics, Bronx Lebanon Hospital Center, Bronx, New York; Pediatric, Adolescent, and Maternal AIDS Branch, National Institute of Child Health and Human Development, Bethesda, Maryland; Pediatric Med- icine Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland; and the Depart- ment of Pediatrics, University of California, San Diego. Financial assistance: Sites were funded through the Pediatric AIDS Clinical Trials Group of the National In- stitute of Allergy and Infectious Diseases, the Pediatric/Perinatal HIV Clinical Trials Network of the Nation- al Institute of Child Health and Human Development, and by Glaxo-Wellcome, Inc. Funding for the RNA testing was provided by Glaxo-Wellcome. Didanosine was provided by Bristol Myers Squibb, and zidovu- dine and 3TC by Glaxo-Wellcome. Submitted for publication Feb 20, 1998; revision received July 16, 1998; accepted Aug 12, 1998. Reprint requests: Ross McKinney, Jr, MD, Box 3461, Duke University Medical Center, Durham, NC 27710. Copyright © 1998 by Mosby, Inc. 0022-3476/98/$5.00 + 0 9/21/93783 AIDS Acquired immunodeficiency syndrome CDC Centers for Disease Control and Prevention CNS Central nervous system ddI Didanosine HIV-1 Human immunodeficiency virus, type 1 PACTG Pediatric AIDS Clinical Trials Group PCR Polymerase chain reaction 3TC Lamivudine ZDV Zidovudine 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 re- sults favoring ZDV/3TC. For patients concurrently randomized to all 3 treatment arms, both ZDV/3TC and ZDV/ddI recip- ients 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 laborato- ry measures, to monotherapy with ddI. (J Pediatr 1998;133:500-8)