       Document 0557
 DOCN  M9460557
 TI    Zidovudine and didanosine combination therapy in children with human
       immunodeficiency virus infection.
 DT    9404
 AU    Husson RN; Mueller BU; Farley M; Woods L; Kovacs A; Goldsmith JC; Ono J;
       Lewis LL; Balis FM; Brouwers P; et al; Pediatric Branch, National Cancer
       Institute, Bethesda, MD 20892.
 SO    Pediatrics. 1994 Feb;93(2):316-22. Unique Identifier : AIDSLINE
       MED/94167185
 AB    OBJECTIVE. Zidovudine and didanosine are both beneficial for the
       treatment of human immunodeficiency virus (HIV) infection in children.
       Because disease progression and toxicity often limit their long-term use
       as single agents, new approaches to using nucleoside analogues are
       necessary to improve current antiretroviral therapy. DESIGN. We
       conducted a phase I-II study to evaluate the tolerance,
       pharmacokinetics, and antiviral activity of the combination of
       zidovudine and didanosine in children with HIV infection. Sixty-eight
       children who were either previously untreated or who had manifested
       hematologic toxicity on full-dose zidovudine were enrolled. Eight dose
       combinations were studied in the previously untreated children, with
       doses of zidovudine ranging from 90 to 180 mg/m2 every 6 hours and doses
       of didanosine ranging from 90 to 180 mg/m2 every 12 hours. RESULTS.
       Fifty-four previously untreated HIV-infected children were enrolled in
       this part of the study, of whom 49 remained in the study for a minimum
       of 24 weeks. For children with previous zidovudine-related hematologic
       toxicity, three dose levels with zidovudine at 60 mg/m2 every 6 hours
       orally and didanosine ranging from 90 to 180 mg/m2 every 12 hours orally
       were used. A total of 14 children were enrolled in this part of the
       study, and 12 remained on therapy for at least 24 weeks. No evidence of
       new or enhanced toxicity was observed in either group. After 24 weeks,
       the median CD4 cell count for all patients increased from 331 to 556
       cells/mm3 (P = .01). For the previously untreated group, the median
       increase in CD4 counts was from 386 to 726 cells/mm3 (P = .003). The
       median p24 antigen concentration (in those with a detectable level at
       baseline) decreased from 95 to < 31 pg/mL (p < .001). The geometric mean
       titer of HIV in plasma decreased from 83.1 to 2.7 tissue culture
       infectious doses/mL (P = .001). CONCLUSIONS. The combination of
       zidovudine and didanosine was well-tolerated at doses as high as those
       used in single agent therapy. Potent in vivo antiviral activity was
       observed. Combination therapy with nucleoside analogues may be an
       important approach to optimizing the use of these agents in the
       treatment of HIV infection.
 DE    Adolescence  Adult  Child  Child, Preschool  Didanosine/ADMINISTRATION &
       DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC  USE  Drug Administration Schedule
       Drug Therapy, Combination  Female  Human  HIV Infections/*DRUG THERAPY
       Infant  Leukocyte Count/DRUG EFFECTS  Male  Support, Non-U.S. Gov't
       Support, U.S. Gov't, P.H.S.  Treatment Outcome  T4 Lymphocytes
       Zidovudine/ADMINISTRATION & DOSAGE/ADVERSE EFFECTS/*THERAPEUTIC  USE
       CLINICAL TRIAL  CLINICAL TRIAL, PHASE I  CLINICAL TRIAL, PHASE II
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

