PRIMARY: To compare the relative safety and tolerance of oral zidovudine (AZT) versus oral stavudine (d4T) in symptomatic HIV-infected children. SECONDARY: To compare the clinical, virologic, and immunologic responses between the two treatment groups, and to obtain pharmacokinetic data for both drugs. At present, AZT is considered the drug of choice for initial treatment of most children with HIV infection, although disease progression or drug intolerance is associated with its long-term use. In preliminary studies in children, d4T, another HIV inhibitor, has been well tolerated, although an optimum dose has not been determined.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Stavudine  Drug: Zidovudine	Phase II

Further Study Details: 

Expected Total Enrollment:  230

At present, AZT is considered the drug of choice for initial treatment of most children with HIV infection, although disease progression or drug intolerance is associated with its long-term use. In preliminary studies in children, d4T, another HIV inhibitor, has been well tolerated, although an optimum dose has not been determined.

Patients are randomized to receive either oral AZT or oral d4T. Treatment continues until the last patient enrolled has received 52 weeks of therapy, or until the study is terminated.

Ages Eligible for Study:  3 Months   -   6 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Concurrent Medication: Recommended:

• PCP prophylaxis.

Allowed:

• Immunoglobulin.
• Erythropoietin, G-CSF, and GM-CSF.
• Corticosteroids.
• Ethionamide or isoniazid for TB if no alternative is available.
• Pyridoxine (up to 50 mg/day) as vitamin supplement.

Patients must have:

• Symptomatic HIV infection.
• No more than 6 weeks of prior antiretroviral or immunomodulator therapy (other than steroids and IVIG).
• Consent of parent or guardian.

NOTE:

• Coenrollment on another ACTG protocol not involving antiretroviral therapy is permitted.

Prior Medication: Allowed:

• Maternal immunomodulator or antiretroviral therapy (including during pregnancy).
• Antiretroviral therapy prior to 2 months.
• Up to 6 weeks of prior antiretroviral therapy or specific immunomodulator therapy (other than corticosteroids and IVIG).

Exclusion Criteria

Co-existing Condition: Patients with the following symptoms or conditions are excluded:

• Current grade 3 or worse neuropathy / lower motor neuropathy.
• Other grade 3 or worse clinical or laboratory toxicities.
• Known intolerance to either AZT or d4T.

Concurrent Medication: Excluded:

• Chemotherapy for active malignancy.

Patients with the following prior conditions are excluded:

• History of grade 3 or worse neuropathy/lower motor neuropathy.

Prior Medication: Excluded:

• More than 6 weeks of prior antiretroviral or immunomodulator therapy.
• Antiretroviral or immunomodulator therapy within 7 days prior to study entry. Ongoing drug or alcohol abuse.

Alabama
      Univ of Alabama at Birmingham Schl of Med / Pediatrics, Birmingham,  Alabama,  35294,  United States
California
      UCSF / Moffitt Hosp - Pediatric, San Francisco,  California,  941430105,  United States
      UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla,  California,  920930672,  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
      Martin Luther King Jr Gen Hosp / UCLA Med Ctr, Los Angeles,  California,  900593019,  United States
      Long Beach Memorial (Pediatric), Long Beach,  California,  90801,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
Colorado
      Children's Hosp of Denver, Denver,  Colorado,  802181088,  United States
Connecticut
      Yale Univ Med School, New Haven,  Connecticut,  06504,  United States
      Univ of Connecticut / Farmington, Farmington,  Connecticut,  06032,  United States
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States
      Children's Hosp of Washington DC, Washington,  District of Columbia,  200102916,  United States
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States
Georgia
      Emory Univ Hosp / Pediatrics, Atlanta,  Georgia,  30306,  United States
Illinois
      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
Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States
Maryland
      Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore,  Maryland,  21201,  United States
Massachusetts
      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
Michigan
      Children's Hosp of Michigan, Detroit,  Michigan,  48201,  United States
New Jersey
      UMDNJ - Robert Wood Johnson Med School / Pediatrics, New Brunswick,  New Jersey,  089030019,  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
      Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl, Camden,  New Jersey,  08103,  United States
New York
      King's County Hosp Ctr / Pediatrics, Brooklyn,  New York,  11203,  United States
      Harlem Hosp Ctr, New York,  New York,  10037,  United States
      SUNY - Brooklyn, Brooklyn,  New York,  11203,  United States
      Cornell Univ Med College, New York,  New York,  10021,  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
      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
      State Univ of New York at Stony Brook, Stony Brook,  New York,  117948111,  United States
      Lincoln Hosp Ctr, Bronx,  New York,  10451,  United States
      Beth Israel Med Ctr / Pediatrics, New York,  New York,  10003,  United States
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  United States
      Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States
Ohio
      Cincinnati Children's Hosp / Univ Hosp, Cincinnati,  Ohio,  452292899,  United States
      Columbus Children's Hosp, Columbus,  Ohio,  432052696,  United States
Pennsylvania
      Children's Hosp of Philadelphia, Philadelphia,  Pennsylvania,  191044318,  United States
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States
Rhode Island
      Rhode Island Hosp / Brown Univ, Providence,  Rhode Island,  02903,  United States
South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States
Tennessee
      Saint Jude Children's Research Hosp of Memphis, Memphis,  Tennessee,  381052794,  United States
Texas
      Children's Med Ctr of Dallas, Dallas,  Texas,  75235,  United States
      Hermann Hosp / Univ Texas Health Science Ctr, Houston,  Texas,  77030,  United States
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States
Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States
Puerto Rico
      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

Study chairs or principal investigators

Kline M,  Study Chair
Van Dyke R,  Study Chair

Study ID Numbers:  ACTG 240
Record last reviewed:  March 1995
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000789
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08