The Safety of Zidovudine Plus Interferon-Alpha in HIV-Infected Children
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      PRIMARY: To determine the maximum tolerated dose of interferon-alfa (IFN-A) alone and in
      combination with zidovudine (AZT); to assess the safety and tolerance of IFN-A alone and in
      combination with AZT.

      SECONDARY: To evaluate the effect of combination IFN-A and AZT on immunologic and virologic
      parameters; to determine whether the pharmacokinetic parameters of AZT are modified by the
      subcutaneous administration of IFN-A.

      AZT is effective in suppressing the progression of HIV infection in patients without symptoms
      or with AIDS or AIDS-related complex (ARC). However, use of AZT is limited by its frequent
      toxicity, which sometimes relates to the amount of drug given. Thus, a combination treatment
      of two drugs that work together may provide more effective and safer treatment. IFN-A is a
      drug that has antiviral effects and may work well with AZT.
    

Detailed description: 
      AZT is effective in suppressing the progression of HIV infection in patients without symptoms
      or with AIDS or AIDS-related complex (ARC). However, use of AZT is limited by its frequent
      toxicity, which sometimes relates to the amount of drug given. Thus, a combination treatment
      of two drugs that work together may provide more effective and safer treatment. IFN-A is a
      drug that has antiviral effects and may work well with AZT.

      The study is being conducted in three stages. In Cohort A (IFN-A alone), four patients
      receive IFN-A; subsequent four-patient cohorts receive doses escalated in increments. If 50
      percent or more of patients at any dose level experience grade 2 or better toxicity, doses in
      subsequent cohorts are escalated. If grade 3 or 4 toxicity is seen in one patient at a given
      dose level, two additional patients are enrolled at that level. Treatment is given
      subcutaneously (under the skin, with a needle), 3 times per week for 12 weeks. The MTD is
      defined as the dose level immediately below that at which 50 percent or more of patients
      experience grade 3 or 4 toxicity. In Cohort B (combination IFN-A plus AZT), patients who
      complete treatment in Cohort A continue on the same dose of IFN-A, and a low, middle, or high
      dose of AZT is added. In Cohort C, four newly assigned patients who have been on a stable
      prescribed dose of AZT of at least 90 mg/m2 for 6 weeks are treated at each of the same dose
      combinations as those in Cohort B. Treatment is given for 12 weeks. IFN-A is given
      subcutaneously 3 times a week and AZT is given orally every 6 hours. Dose levels of both
      drugs are increased until 50 percent or more of patients experience grade 3 or 4 toxicity in
      any dose level.
    

Intervention name(s): Interferon alfa-2a; Zidovudine
Intervention type(s): Drug; Drug
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Zidovudine
Primary purpose: Treatment
Keywords: Drug Therapy, Combination; AIDS-Related Complex; Zidovudine; Interferon Type I