A Study of Ritonavir (an Anti-HIV Drug) in HIV-Positive Infants and Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The study examines the safety and effectiveness of ritonavir (an anti-HIV drug), alone and in
      combination with other anti-HIV drugs, in HIV-positive children under 2 years of age. This
      study will also determine the most effective doses of ritonavir for future pediatric HIV
      studies.

      Infants infected with HIV by their mothers experience faster disease progression than adults
      or older children. Treatment with anti-HIV drugs administered at an early age may slow
      disease progression in infant populations.
    

Detailed description: 
      As a group, vertically infected children experience more rapid disease progression than
      children infected at an older age or adults. The early administration of potent
      antiretroviral regimens might significantly impact the course of vertical HIV-1 infection.

      Infants and children are stratified by age, representative of the developmental differences
      related to drug metabolism (Group I: at least 6 months - 2 years, Group II: 3-6 months, Group
      IIIA: 1 month - 10 weeks, IIIB: 1 month - less than 3 months). Within each age group there
      will be two possible dosage cohorts. All age groups will be enrolled simultaneously into
      dosage Cohort I, at the initial drug dosage. Progression to Cohort II (at a higher or lower
      drug dosage) will be decided according to safety, tolerance or viral load in Cohort I. All
      therapy for Group I/II, whether in Cohort I or II, will be introduced as follows: single dose
      of ritonavir on Day 0, ritonavir monotherapy through Day 7 AM and combination therapy from
      Day 7 PM through Week 104. All therapy for Group IIIA & IIIB, whether in Cohort I or II, will
      be introduced as follows: single dose of ritonavir on Day 0 AM and transition to combination
      therapy Day 0 PM through Week 104. NOTE: Progression to combination therapy for Group IIIA
      infants is dependent upon the results of the single-dose ritonavir pharmacokinetics (PK). If
      the patient is no longer at least presumed to be HIV-infected, he/she will be discontinued
      from the study. Replacement infants, who will not receive the single dose of ritonavir, will
      be acquired from Group IIIB infants; new infants that are either presumed HIV infected or
      have already been shown to be HIV-infected. Clinical evaluations are conducted and blood and
      urine samples collected regularly during the treatment period in order to quantify HIV-1
      levels and determine body chemistries. Pharmacokinetic studies require additional blood
      sampling up to Week 16. [AS PER AMENDMENT 6/30/98: Pharmacokinetics data from Cohort I showed
      that the proposed Cohort II starting dose was too low. The dose for Cohort II is now
      increased. All subjects in Groups I, II, and III will begin combination therapy on Day 0 at
      the increased dose.] [AS PER AMENDMENT 3/13/00: The study has been extended for an additional
      104 weeks, provided the patient's viral load is undetectable (below 400 copies/ml) at the end
      of the initial study period. While on the treatment extension, patients must continue their
      current schedule for study drug administration and completion of study visits.]
    

Intervention name(s): Ritonavir; Lamivudine; Zidovudine
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Ritonavir; Lamivudine; Zidovudine
Primary purpose: Treatment
Keywords: Dose-Response Relationship, Drug; Drug Therapy, Combination; Zidovudine; HIV Protease Inhibitors; Ritonavir; Lamivudine; Anti-HIV Agents