Safety, Tolerability, and Anti-HIV Activity of PEG-Intron in HIV-Positive Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to see if PEG-Intron is safe and tolerated when given to
      children, to see how much gets into the blood and how long it stays in the blood, and to see
      how well it works to reduce viral load (level of HIV in the blood).

      PEG-Intron is an experimental drug that works differently than other anti-HIV medications. It
      decreases the ability of HIV to infect the T cells (a special type of cell that helps fight
      infection). PEG-Intron has been approved by the Food and Drug Administration (FDA) to treat
      hepatitis C in adults, but in this study, it is being used as an investigational agent for
      the treatment of HIV/AIDS. It has not been tested in children before and experience with
      PEG-Intron in adults is limited. (This protocol has been changed to reflect FDA approval of
      PEG-Intron for treating hepatitic C in adults.)
    

Detailed description: 
      The current optimal clinical management of HIV infection involves therapy with combinations
      of nucleoside and nonnucleoside reverse transcriptase inhibitors and HIV protease inhibitors.
      These regimens, though effective, do not completely eliminate HIV and the development of drug
      resistance is a major clinical problem. Interferons have been proposed as a possible
      treatment of HIV. Interferon-alfa inhibits HIV replication in vitro, and HIV-infected
      patients appear to have reduced production of interferons. Previous short-term clinical
      studies in adults showed anti-HIV activity, although there were safety and tolerability
      problems associated with the higher dose regimens used. This study will utilize a rising
      multiple-dose design to assess the safety, tolerability, and pharmacokinetics of single and
      multiple doses of PEG-Intron in HIV-infected children.

      In a dose-escalation study, patients add weekly PEG-Intron to their antiretroviral therapy
      for up to 6 weeks. The first 2 doses are received in the clinic where parents/guardians are
      trained to administer injections, and succeeding doses are given at home.

      Patients are enrolled from 2 cohorts. An older cohort of ages 2 to 16 years receives
      PEG-Intron at the lowest drug level. If the dose is tolerated, patients are added and if
      safety criteria are met, patients are enrolled in the next higher dose level. The dose level
      will be increased similarly for up to 4 doses. An optimal dose level is chosen.

      Cohort II patients are a younger group ranging from 3 months to under 2 years of age.
      Patients initially receive the next lower PEG-Intron dose to the optimal dose identified in
      Cohort I [AS PER AMENDMENT 07/23/01: or 1 microg/kg if the optimal dose proves to be 1
      microg/kg]. If this dose is safely tolerated, additional patients are added. If this dose
      level meets safety criteria, patients are enrolled to receive the optimal dose level.
      Patients are evaluated with the same safety criteria as Cohort I. Patients in both cohorts
      who have at least a 0.5 log reduction in HIV RNA at 28 days of treatment are offered
      continued treatment for a total of 60 weeks.
    

Intervention name(s): Peginterferon alfa-2b
Intervention type(s): Drug
Intervention MeSH terms: Peginterferon alfa-2b
Primary purpose: Treatment
Keywords: Polyethylene Glycols; Interferon Alfa-2b; HIV-1; Dose-Response Relationship, Drug; Drug Therapy, Combination; Virus Inhibitors; Anti-HIV Agents; Pharmacokinetics