Both ritonavir (RTV) and indinavir (IDV) are approved by the FDA to treat HIV, but IDV has not been approved for use in children and the doses for the combination of the two drugs has not been studied in children. The purpose of this study is to find a combination of RTV and IDV that is safe, well tolerated, and produces drug levels in the blood of children that are comparable to effective drug levels in the blood of adults. The effectiveness of the drug combination in decreasing the amount of virus in the body will also be studied. The children enrolled in this study will have high HIV viral loads despite taking anti-HIV drugs.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: indinavir sulfate  Drug: ritonavir	Phase I Phase II

Further Study Details: 

Expected Total Enrollment:  36

Combination regimens of RTV and IDV in adults offer the benefit of two potent antiretroviral agents, convenience of twice-daily dosing, unrestricted timing of meals, and fewer renal complications. There are limited, largely anecdotal data from children suggesting that initial virologic response can also be attained in children given IDV with RTV, but there are not sufficient pharmacokinetic data to define appropriate dose regimens. This study will evaluate the clinical feasibility of a combination RTV and IDV regimen for children.

Patients will be stratified on the basis of age/Tanner stage and ability to swallow intact capsules. Patients will be randomized to either Balanced Dose or Low Dose RTV treatment arms. Patients in the Balanced Dose Arm will receive RTV and IDV in approximately equal doses. The Low Dose RTV Arm will receive a dosing ratio of RTV:IDV of approximately 1:3. Patients will have scheduled study visits every 4 weeks for 6 months, then every 3 months for approximately 18 months. Study visits will consist of a medical history, physical exam, and blood and urine tests. Patients will have intensive pharmacokinetic analysis at Week 4 (or 2 weeks after a stable dose of study drugs has been reached) and Week 16. Study visits that include pharmacokinetic analysis will last 9 to 13 hours.

At each study visit, patients will be closely assessed for drug toxicity and virologic response. At the end of the study, patients with good virologic response and no evidence of toxicity may choose to enter a 48 week extension phase and continue taking the combination regimen.

Ages Eligible for Study:  2 Years   -   17 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

• HIV infection
• HIV RNA levels > 10,000 copies/ml within 30 days prior to study entry
• Anti-HIV drug therapy failure while on the same anti-HIV drugs for more than 16 weeks
• Body size above a certain limit (body surface area > 0.48 m2)
• Acceptable methods of contraception
• Consent of parent or legal guardian

Exclusion Criteria

• Unable to determine HIV genotypic resistance
• HIV resistant to IDV or RTV at study screening
• Previously received IDV and RTV at the same time
• Need treatment with any medication prohibited by the study
• Glucocorticoids for more than 14 days at study entry
• Cancer requiring chemotherapy
• Drugs affecting the immune system, other than IVIG, within 3 months of study entry
• Certain abnormal laboratory results at study entry
• Pregnant or breast-feeding
• Unable to be followed at a PACTG center during the trial

California
      UCSF / Moffitt Hosp - Pediatric, San Francisco,  California,  941430105,  United States
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States
      Univ of California, San Diego, San Diego,  California,  92103,  United States
Connecticut
      Yale Univ Med School, New Haven,  Connecticut,  06504,  United States
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States
      Univ of Florida Gainesville, Gainesville,  Florida,  32610,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  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
Massachusetts
      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
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
New York
      Harlem Hosp Ctr, New York,  New York,  10037,  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
      Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx,  New York,  10461,  United States
      Metropolitan Hosp Ctr, New York,  New York,  10029,  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
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  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
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States
Virginia
      Med College of Virginia, Richmond,  Virginia,  23219,  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

Study chairs or principal investigators

Ellen Chadwick,  Study Chair
Ram Yogev,  Study Chair
Stephen Pelton,  Study Chair
Elaine Abrams,  Study Chair

Study ID Numbers:  ACTG P1013; PACTG P1013
Record last reviewed:  August 2004
Last Updated:  April 7, 2005
Record first received:  March 10, 2001
ClinicalTrials.gov Identifier:  NCT00012519
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08