To evaluate the safety and determine the pharmacokinetic disposition of stavudine (d4T) alone and in combination with didanosine (ddI), and whether concurrent administration alters the disposition of either drug. To compare d4T versus d4T plus ddI with respect to short and long term changes from baseline in plasma HIV RNA concentrations. To determine the relationship, if any, between drug exposure and viral burden. In a pilot study of d4T and ddI given to eight children with advanced HIV for 24 weeks, the three children with baseline counts greater than 50 cells/micro liter experienced a 20% increase in their CD4+ lymphocyte counts. Based on these results, controlled trials of the same regimen for children with less advanced HIV disease should be undertaken.

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

Further Study Details: 

Expected Total Enrollment:  198

In a pilot study of d4T and ddI given to eight children with advanced HIV for 24 weeks, the three children with baseline counts greater than 50 cells/micro liter experienced a 20% increase in their CD4+ lymphocyte counts. Based on these results, controlled trials of the same regimen for children with less advanced HIV disease should be undertaken.

Eligible subjects receiving d4T will be assigned in an open manner to Arm 1, and subjects who have been receiving zidovudine (AZT) will be assigned in a randomized, double blind manner to Arms 2 and 3. Each subject will receive study drug for 48 weeks as follows: Arm 1 - d4T plus ddI, Arm 2 - d4T alone, Arm 3 - d4T plus ddI.

Ages Eligible for Study:  6 Months   -   10 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Patients must:

• Be on-study, on-treatment in ACTG 240, or receiving AZT monotherapy by prescription for at least 6 months immediately preceding enrollment.
• Have laboratory evidence of HIV-1 infection < 18 months - 2 positive viral tests >= 18 months - 2 positive viral tests or 2 or more positive tests for HIV antibody
• Have parent or legal guardian willing to sign a consent.

Prior Medication: Required:

• On-study, on-treatment in ACTG 240 (D4T or AZT) or receiving AZT monotherapy by prescription for at least six months immediately preceding this trial.

Exclusion Criteria

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

• Intractable diarrhea or vomiting.
• Current clinical or laboratory Grade 3 or worse toxicities.

Concurrent Medication: Excluded:

• Concurrent use of antiretroviral agents other than those provided by the study, immunomodulators (other than IVIG or corticosteroids), or other investigational drugs except for those in ACTG 254 and ACTG 219.
• Chemotherapy for active malignancy.

Patients with any of the following prior conditions are excluded:

• Reached an ACTG 240 defined endpoint, or are permanently off ACTG 240 study treatment.
• Prescription AZT recipients may not have received > 6 weeks of d4T or ddI previously.
• Subjects who have had chemotherapy for active malignancy.

Prior Medication: Excluded:

• Prescription AZT recipients may not have received > 6 weeks of d4T or ddI previously.

California
      Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles,  California,  905022004,  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
Colorado
      Children's Hosp of Denver, Denver,  Colorado,  802181088,  United States
Connecticut
      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
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  United States
      Cook County Hosp, 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
Michigan
      Children's Hosp of Michigan, Detroit,  Michigan,  48201,  United States
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States
      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
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
      North Shore Univ Hosp, Great Neck,  New York,  11021,  United States
      Schneider Children's Hosp, New Hyde Park,  New York,  11040,  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
      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
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  United States
Pennsylvania
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States
South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States
Texas
      Children's Med Ctr of Dallas, Dallas,  Texas,  75235,  United States
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  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 327
Record last reviewed:  April 1997
Last Updated:  April 7, 2005
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000851
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08