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. 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.

Growth as a prognostic indicator in children with human immunodeficiency virus infection treated with zidovudine. AIDS Clinical Trials Group Protocol 043 Study Group.

OBJECTIVE: To assess measures of growth as prognostic indicators in response to zidovudine treatment in children with symptomatic human immunodeficiency virus infection. METHODS: We retrospectively assessed data from AIDS Clinical Trials Group Protocol 043, an open-label, phase II study of oral zidovudine therapy (180 mg/m2 per dose every 6 hours) in children with human immunodeficiency virus who have severe symptoms. Several variables were evaluated for their prognostic significance: CD4+ lymphocyte percentage; rates of weight gain and linear growth; entry weight, height, and weight-for-height z scores for age; race; gender; age; and route of transmission. RESULTS: The overall survival rate as of April 1, 1992 (4 years after study initiation), was 44%, with a median survival of 37.9 months. The risk of death was greatest in children with CD4+ lymphocyte percentages < 20% (relative risk, 3.49), but was also increased in children who had a weight-for-age z score < -2 on entry to the study (relative risk, 1.53) and in those who failed to gain weight at the 25th percentile rate or greater during the first 6 months of therapy (relative risk, 2.03). These three factors, as well as race and gender, were found to be significant predictors in a multivariate, proportional-hazards model of survival. Entry height-for-age and height growth rates did not have predictive value for survival in univariate or multivariate analyses. CONCLUSIONS: Weight-for-age and rate of weight gain are important, easily obtained, and inexpensive prognostic indicators in children with symptomatic human immunodeficiency virus treated with zidovudine. Both were less predictive of survival than the entry CD4+ lymphocyte percentage.

Effect of human immunodeficiency virus infection on the growth of young children. Duke Pediatric AIDS Clinical Trials Unit.

We retrospectively analyzed the growth of 170 children less than 25 1/2 months of age who were referred for evaluation of human immunodeficiency virus (HIV) antibody status. By the age of 4 months, the 62 HIV-infected children were significantly smaller than the 108 uninfected children in both weight-for-age and length-for-age measurements; linear growth and weight gain were proportionally decreased.

Safety and tolerance of intermittent intravenous and oral zidovudine therapy in human immunodeficiency virus-infected pediatric patients. Pediatric Zidovudine Phase I Study Group.

Thirty-five children with symptomatic human immunodeficiency virus infection were enrolled in a 12-week, three-center phase I study of intravenous and oral zidovudine therapy. At enrollment the children ranged in age from 5 months to 13 years, with a median age of 3 1/2 years. Twenty-one children (60%) had acquired immunodeficiency syndrome and 14 (40%) had the related complex; 20 children had less than 0.5 10(9) CD4+ lymphocytes per liter (less than 500 cells/mm3) at entry. Zidovudine was administered in one of three escalating dose regimens. One or two months of intravenous treatment with zidovudine every 6 hours was followed by orally administered drug on the same schedule; zidovudine was infused at 80, 120, or 160 mg/m2/dose, and the oral dose was one and one-half times the intravenous dosage. Adverse events were similar to those observed in adults. Neutropenia (absolute neutrophil count less than 0.75 10(9)/L (750 cells/mm3] occurred in nine patients. The median neutrophil count fell from 2.50 10(9)/L at entry to 1.72 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven 10(9)/L at the end of the study. Anemia requiring transfusion occurred in seven patients; the median hemoglobin level among nontransfused patients decreased from an entry value of 108 to 105 gm/L (10.8 to 10.5 gm/dl). Dosage adjustments were made in 15 patients, in 12 because of anemia or neutropenia. No patients required permanent discontinuation of zidovudine because of toxic effects. Positive effects included a faster-than-anticipated rate of weight gain, decreased hepatosplenomegaly, and lowering of the total IgG and IgM concentrations toward more normal values. Zidovudine appears to be safe and to have manageable toxic effects in children.