PRIMARY: To determine safety, tolerance, and pharmacokinetics of zidovudine (AZT) and
zalcitabine (dideoxycytidine; ddC) when given in combination in clinically stable AZT-treated
children.
SECONDARY: To compare combination therapy with mono drug therapy for antiviral activity and
laboratory markers of disease progression, as determined by virologic and immunologic
determinations. To evaluate the influence of combination therapy on disease progression as
determined by evaluation of clinical criteria.
In children currently being treated with AZT, it is unknown whether the addition of another
antiretroviral agent such as ddC would help increase efficacy and tolerance. This study will
examine the possible advantages of combination AZT/ddC therapy over monotherapy with AZT
alone.
Patients are stratified according to duration of ongoing AZT therapy and are randomized to
receive AZT either alone or in combination with ddC. Patients receive therapy until the last
patient enrolled completes 32 weeks of therapy. The study may be extended for two additional
32-week periods on an optional basis.
Inclusion Criteria
Concurrent Medication:
Recommended:
- PCP prophylaxis.
Allowed:
- Intravenous and/or intramuscular immunoglobulin.
- Acyclovir (no more than 30 mg/kg/day PO).
- Ketoconazole (no more than 10 mg/kg/day).
- Nystatin.
- Aspirin, acetaminophen, nonsteroidal anti-inflammatory drugs, sedatives, and
barbiturates, not to exceed 72 hours.
- Isoniazid in combination with pyridoxine, provided there is no evidence of peripheral
neuropathy.
- Trimethoprim / sulfamethoxazole.
- Amphotericin B (no more than 1 mg/kg for 5 days/week).
- Aerosolized ribavirin for bronchiolitis.
- Hematopoietic agents.
- Other drugs with little nephro-, hepato-, or cytotoxicity.
- Nutritional support for HIV wasting syndrome or malnutrition.
Patients must have:
- HIV infection.
- Ongoing stable AZT therapy.
Exclusion Criteria
Co-existing Condition:
Patients with the following symptoms and conditions are excluded:
- Disease progression while on AZT, to the extent that the patient meets the criteria
for advanced disease protocols.
- Known allergy or sensitivity to ddC.
- Cardiomyopathy.
Concurrent Medication:
Excluded:
- Biologic modifiers other than IVIG, steroids, or hematopoietic agents.
- Investigational medications unless approved by protocol chair.
- Medications known to cause pancreatitis (unless ddC is interrupted while these
medications are given).
Patients with the following prior conditions are excluded:
- History of intolerance or toxicity to AZT.
- History of symptomatic pancreatitis.
- History of peripheral neuropathy or abnormal nerve conduction velocity test.
Prior Medication:
Excluded:
- Antiretroviral agents other than AZT within 2 weeks of study entry.
Required:
- Ongoing stable AZT therapy for more than 6 weeks duration.
San Juan City Hosp, San Juan 009367344, Puerto Rico
Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan 009365067, Puerto Rico
Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon 00956, 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
Stanford Univ School of Medicine / Pediatrics, Stanford, California 943054149, 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
UCLA Med Ctr / Pediatric, Los Angeles, California 900951752, United States
Cedars Sinai / UCLA Med Ctr, Los Angeles, California 900481804, 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
Yale Univ Med School, New Haven, Connecticut 06504, 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
Georgetown Univ Med Ctr, Washington, District of Columbia 20007, United States
Univ of Miami (Pediatric), Miami, Florida 33161, United States
Emory Univ Hosp / Pediatrics, Atlanta, Georgia 30306, 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
Boston City Hosp / Pediatrics, Boston, Massachusetts 02118, 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
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
King's County Hosp Ctr / Pediatrics, Brooklyn, New York 11203, United States
SUNY - Brooklyn, Brooklyn, New York 11203, United States
North Shore Univ Hosp, Great Neck, New York 11021, United States
Westchester Hosp, Valhalla, New York 10595, 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
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Mount Sinai Med Ctr, New York, New York 10029, 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
Albert Einstein College of Medicine, Bronx, New York 10461, 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
Lincoln Hosp Ctr, Bronx, New York 10451, United States
Children's Hosp Pact Prog / Children's Hosp of Buffalo, Buffalo, New York 14222, United States
Duke Univ Med Ctr, Durham, North Carolina 277103499, United States
Columbus Children's Hosp, Columbus, Ohio 432052696, United States
Sunnybrook Health Science Ctr, Toronto, Ontario, Canada
Children's Hosp of Philadelphia, Philadelphia, Pennsylvania 191044318, United States
Saint Christopher's Hosp for Children, Philadelphia, Pennsylvania 191341095, United States
Rhode Island Hosp / Brown Univ, Providence, Rhode Island 02903, United States
Med Univ of South Carolina, Charleston, South Carolina 294253312, United States
Children's Hospital & Medical Center / Seattle ACTU, Seattle, Washington 981050371, United States
Bakshi SS, Britto P, Capparelli E, Mofenson L, Fowler MG, Rasheed S, Schoenfeld D, Zimmer B, Frank Y, Yogev R, Jimenez E, Salgo M, Boone G, Pahwa SG. Evaluation of pharmacokinetics, safety, tolerance, and activity of combination of zalcitabine and zidovudine in stable, zidovudine-treated pediatric patients with human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 190 Team. J Infect Dis. 1997 May;175(5):1039-50.
Dankner WM, Lindsey JC, Levin MJ. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J. 2001 Jan;20(1):40-8.
