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.
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.
McKinney
R E
RE
Department of Pediatrics and Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Johnson
G M
GM
Stanley
K
K
Yong
F H
FH
Keller
A
A
O'Donnell
K J
KJ
Brouwers
P
P
Mitchell
W G
WG
Yogev
R
R
Wara
D W
DW
Wiznia
A
A
Mofenson
L
L
McNamara
J
J
Spector
S A
SA
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*
D019380:Anti-HIV Agents; D015704:CD4 Antigens; D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D016049:Didanosine