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.
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.
Inclusion Criteria
Concurrent Medication:
Recommended:
- PCP prophylaxis.
Allowed:
- Acetaminophen if not on a continual basis.
NOTE:
- Drugs that are metabolized by hepatic glucuronidation or that are associated with
occurrence of pancreatitis are allowed but should be used with caution.
Patients must have at least one of the following:
- Documented HIV infection.
- Been born to an HIV-infected woman and receiving AZT.
PER AMENDMENT 4/8/97:
- Number 2 above no longer required with closure of Part A of study.
- Patients must have signed, informed consent of parent or legal guardian.
PER 6/20/95 AMENDMENT, patients in Part A must be less than 28 days of age and those in
Part B must be less than 90 days of age.
PER 7/7/94 AMENDMENT, patients in Part A were less than 120 days of age and those in Part B
were less than 180 days of age.
NOTE:
- All patients must have been more than 34 weeks gestation at birth.
Prior Medication:
Allowed:
- Prior vaccine therapy.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms or conditions are excluded:
- Pancreatitis.
- Clinically unstable condition.
- Current participation on a vaccine trial or, for Part A, a perinatal trial if of
indeterminate infection status.
Concurrent Medication:
Excluded:
- Vaccine therapy.
Patients with the following prior condition are excluded:
- Pancreatitis at any time since birth.
Prior Medication:
Excluded in Part B patients only:
- More than 90 days of prior antiretroviral or immunomodulator therapy, exclusive of
therapy received in utero.
San Juan City Hosp, San Juan 009367344, Puerto Rico
Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan 009365067, Puerto Rico
Univ of Alabama at Birmingham Schl of Med / Pediatrics, Birmingham, Alabama 35294, United States
UCSF / Moffitt Hosp - Pediatric, San Francisco, California 941430105, United States
UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla, California 920930672, United States
San Francisco Gen Hosp, San Francisco, California 94110, United States
Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles, California 905022004, United States
Children's Hosp of Oakland, Oakland, California 946091809, United States
Long Beach Memorial (Pediatric), Long Beach, California 90801, United States
Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States
Children's Hosp of Denver, Denver, Colorado 802181088, United States
Univ of Connecticut / Farmington, Farmington, Connecticut 06032, United States
Howard Univ Hosp, Washington, District of Columbia 20060, United States
Children's Hosp of Washington DC, Washington, District of Columbia 200102916, United States
Univ of Miami (Pediatric), Miami, Florida 33161, United States
Univ of Florida Health Science Ctr / Pediatrics, Jacksonville, Florida 32209, United States
North Broward Hosp District, Fort Lauderdale, Florida 33311, United States
Palm Beach County Health Dept, Riviera Beach, Florida 33404, United States
Chicago Children's Memorial Hosp, Chicago, Illinois 606143394, United States
Cook County Hosp, Chicago, Illinois 60612, United States
Univ of Illinois College of Medicine / Pediatrics, Chicago, Illinois 60612, United States
Univ of Chicago Children's Hosp, Chicago, Illinois 606371470, United States
Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, United States
Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore, Maryland 21201, United States
Children's Hosp of Boston, Boston, Massachusetts 021155724, United States
Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States
Univ of Massachusetts Med School, Worcester, Massachusetts 016550001, United States
Children's Hosp of Michigan, Detroit, Michigan 48201, United States
Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark, New Jersey 071032714, United States
Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl, Newark, New Jersey 071072198, United States
Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl, Newark, New Jersey 07103, United States
Harlem Hosp Ctr, New York, New York 10037, United States
Schneider Children's Hosp, New Hyde Park, New York 11040, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Columbia Presbyterian Med Ctr, New York, New York 10032, United States
Mount Sinai Med Ctr / Pediatrics, New York, New York 10029, United States
Metropolitan Hosp Ctr, New York, New York 10029, United States
Children's Hosp at Albany Med Ctr, Albany, New York 12208, United States
SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse, New York 13210, United States
Bronx Lebanon Hosp Ctr, Bronx, New York 10457, United States
Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York, New York 10032, United States
Duke Univ Med Ctr, Durham, North Carolina 277103499, United States
Children's Hosp of Philadelphia, Philadelphia, Pennsylvania 191044318, United States
Saint Christopher's Hosp for Children, Philadelphia, Pennsylvania 191341095, United States
Med Univ of South Carolina, Charleston, South Carolina 294253312, United States
Children's Hosp of the King's Daughters, Norfolk, Virginia 23507, United States
Med College of Virginia, Richmond, Virginia 23219, United States
McKinney RE Jr. Ongoing and future trials of antiretroviral therapy in the pediatric AIDS clinical trials group (PACTG). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:173
