A Study of Didanosine Use Alone or in Combination With Zidovudine in Infants Exposed to or Infected With HIV

Overview

To determine the pharmacokinetics, safety, and efficacy of didanosine (ddI) alone or in combination with zidovudine (AZT) in HIV-infected infants. PER AMENDMENT 4/8/97: Part A study objectives are completed. Part B objectives: To assess the safety, toxicity, and tolerability and to compare anti-HIV activity, as measured by change in log10 RNA, of the two study arms. Early treatment of HIV-infected infants with antiretroviral agents may prevent the early and rapid decline of CD4 count and immunologic function. Combination therapy may be preferred over monotherapy, since resistance to a single agent can develop rapidly. Currently, there is little information on ddI monotherapy in young infants less than 90 days and no information on the use of combination therapy in this population.

Early treatment of HIV-infected infants with antiretroviral agents may prevent the early and rapid decline of CD4 count and immunologic function. Combination therapy may be preferred over monotherapy, since resistance to a single agent can develop rapidly. Currently, there is little information on ddI monotherapy in young infants less than 90 days and no information on the use of combination therapy in this population. In Part A, a cohort of patients younger than 28 days (was less than 120 days; amended 6/20/95) of age receives open-label ddI monotherapy for 1 week before initiation of AZT/ddI combination therapy. After pharmacokinetic data are obtained, an additional cohort of patients receives ddI at a higher dose. An age-adjusted dose for ddI is determined for use in Part B. (NOTE: As of 2/13/95, Part A has completed accrued for infants 29 to 120 days of age.) Part B patients less than 90 days of age (was less than 180 days of age; amended 6/20/95) are randomized, on a double-blind basis, to receive ddI or AZT/ddI. All patients continue treatment until 12 months after the last patient on Part B is enrolled. PER AMENDMENT 4/8/97: Part A of this protocol is closed with accrual objectives met. Part B of the study will remain open for patient accrual until 6/2/97. Part B is designed as a 2-arm, randomized, double-blind study to assess safety, toxicity and tolerability as well as anti-HIV activity of ddI or AZT/ddI.