A RANDOMIZED STUDY OF COMBINED ZIDOVUDINE-LAMIVUDINE VERSUS DIDANOSINE MONOTHERAPY IN CHILDREN WITH SYMPTOMATIC THERAPY-NAIVE HIV-1 INFECTION

Objective: The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 3 00 assessed the clinical efficacy and safety of combination zidovudine /lamivudine (ZDV/3TC) compared with either didanosine (ddI) alone or c ombination ZDV/ddI. Study design: Children with symptomatic human immu nodeficiency virus (HIV) infection, 6 weeks through 15 years of age, w ere stratified according to age and randomly assigned to receive ddI, ZDV/3TC, or ZDV/ddI. The primary endpoint was time to first progressio n 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 evalua ted, 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 p rogression 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). Wei ght and height growth rates, CD4(+) cell counts, and RNA concentration s showed results favoring ZDV/3TC. For patients concurrently randomize d to all 3 treatment arms, both ZDV/3TC and ZDV/ddI recipients had low er 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 LS clinical and labora tory measures, to monotherapy with ddI.