the safety of zidovudine plus interferon-alpha in hiv-infected children

Conditions: HIV Infections

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.

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.

Eligibility criteria:
inclusion criteria concurrent medication: recommended: * prophylaxis for pneumocystis carinii pneumonia. allowed: * aerosol ribavirin for short-term treatment of acute respiratory syncytial virus (rsv). * immunization according to the current recommendations of the advisory committee for immunization practice. * ivig. systemic ketoconazole, acyclovir, or oral nystatin for acute therapy. patients must have the following: * hiv infection. patients with proven resistance to azt are also eligible. prior medication: allowed: * aerosol ribavirin. required: cohort c treatment: * stable prescribed dose of zidovudine (azt) \>= 90 mg/m2 for at least 6 weeks prior to study entry. exclusion criteria co-existing condition: patients with the following conditions or symptoms are excluded: aids or class p-2b, d, or e symptomatic infection. concurrent medication: excluded: * hepatotoxic or neurotoxic drugs, immunosuppressants, or antiseizure medication. ketoconazole, fluconazole, and acyclovir for prophylaxis. immunomodulators (other than ivig). experimental drugs. cohort a patients: * azt for clinical indications. prior medication: excluded: * other antiretroviral agents (including didanosine (ddi), dideoxycytidine (ddc), or soluble cd4) within 1 month of study entry. systemic ribavirin administered for retroviral therapy within 2 months of study entry. * immunomodulating agents including interferon, isoprinosine, interleukin-2, or lymphocyte transfusions within 4 weeks of study entry. * rbc transfusion within 4 weeks prior to study entry. alcohol or drug abuse.

Keywords: drug therapy, combination aids-related complex zidovudine interferon type i