EVALUATION OF PHARMACOKINETICS, SAFETY, TOLERANCE, AND ACTIVITY OF COMBINATION OF ZALCITABINE AND ZIDOVUDINE IN STABLE, ZIDOVUDINE-TREATED PEDIATRIC-PATIENTS WITH HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION

A double-blind phase II trial compared zalcitabine (0.03 mg/kg/day) in combination with zidovudine (720 mg/m(2)/day) and zidovudine monother apy in 250 clinically stable, previously zidovudine-treated, human imm unodeficiency virus-infected children, The combination was well-tolera ted except for an increased incidence of neutropenia (14%) compared wi th that in children receiving monotherapy (5%), No differences were no ted for time to first AIDS-defining illness or death, neuropsychologic status, or weight Z scores, In patients in the combination arm, the C D4 cell count decline was slower (13% per year) than in patients recei ving monotherapy (25% per year) (P = .03), and quantitative peripheral blood mononuclear cell virus load remained lower at all time points ( P = .08), Deaths were fewer in patients receiving combination therapy (4) compared with those in patients receiving monotherapy (10) (P = .0 83), Thus, administration of zidovudine with zalcitabine to children w ith prior zidovudine treatment did not result in a significant increas e in toxicity compared with that resulting from zidovudine monotherapy and demonstrated improvement in immunologic and virologic surrogate m arkers.