The purpose of this study is to find a safe and tolerable dose of the protease inhibitor (PI) atazanavir (also known as BMS-232632 or ReyatazTM), with or without a low-dose boost of the PI ritonavir, when taken with other anti-HIV drugs in HIV-infected infants, children, and adolescents. Advancements in anti-HIV drugs for HIV-positive children and adolescents have been hard to make, in part because these patients often do not take the drugs as prescribed. Atazanavir may be a better option for these patients because it is available in the form of powder which children and adolescents may be more willing to take regularly. Using a low dose of ritonavir as a boosting agent for atazanavir may also increase the chances of virologic response of highly active antiretroviral treatment (HAART)-experienced patients. This study will try to find safe and tolerable doses of atazanavir with or without low-dose ritonavir boost in infants, children, and adolescents. For this study, patients will be enrolled in the U.S. and South Africa.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Atazanavir  Drug: Ritonavir	Phase I

Further Study Details: 

Expected Total Enrollment:  152

Advancements in HAART for HIV-infected children and adolescents are hindered by patient nonadherence. The availability of a powder formulation and the once-daily dosing schedule make atazanavir an attractive agent for improved adherence in pediatric treatment regimens. This study is designed to provide pharmacokinetic data to guide dosing recommendations for atazanavir, when given concurrently with or without low-dose ritonavir boost, in infants, children, and adolescents. During the study, the safety and tolerance of atazanavir (with or without low-dose ritonavir) will be closely monitored, and virologic efficacy data will be obtained.

There are two parts to this study. Step I is open in the U.S. and South Africa, and is further divided into two groups, Parts A and B. Part A participants will receive atazanavir only and part B participants will receive atazanavir with low-dose ritonavir boost. Patients receive atazanavir once a day with 2 other antiretroviral drugs (not provided by the study), and in part B patients only (Groups 5 to 8), atazanavir is given with a low dose of ritonavir. Patients are placed into 1 of 8 groups (Groups 1 to 4 for part A; Groups 5 to 8 for part B) with respect to age and study drug formulation. Patients in Groups 1 and 5 are infants age 3 months and 1 day (91 days) up to 2 years (less than or exactly 730 days) and take atazanavir in powder form. Patients in Groups 2, 3, 6, and 7 are children age 2 years and 1 day (731 days) or more up to 13 years. Groups 2 and 6 receive atazanavir in powder form, while Groups 3 and 7 receive the capsule form. Patients in Groups 4 and 8 are adolescents age 13 years and 1 day up to 21 years (not including the 22nd birthday) and take atazanavir in capsule form.

For each group, enrollment starts with 5 patients per group, with all patients evaluated for pharmacokinetic and safety criteria, adjusting the dose until one is found that passes both sets of criteria. Then 5 additional patients are enrolled, with enrollment continuing for each group once all patients within that group meet the pharmacokinetics criteria. Clinic visits are every 4 weeks through Week 48, then every 8 weeks until the last patient to enroll in the study has reached Week 96 of his/her treatment. At every visit, patients undergo a complete medical history and physical exam, cardiac conduction evaluation, and urine and blood collection. Patients of childbearing age have a pregnancy test performed at each visit.

Step II is open only to South African participants of Step I who have responded to treatment by the end of Step I. All such participants will be given atazanavir in capsule form at the same dose they received at the end of Step I, as well as the other antiretrovirals they were receiving during the course of Step I. Step II will continue until atazanavir is approved in South Africa and readily available by individual prescription and participants will have a study visit every 12 months.

Ages Eligible for Study:  3 Months   -   21 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

[Note: Groups 1 and 2 are no longer open to accrual.]

• Have HIV infection.
• Have a viral load (amount of HIV in the blood) of 5,000 copies/ml or more.
• Are able to take 2 NRTIs that they have never taken before.
• Take a test showing they can respond to atazanavir.
• Are able and willing to swallow the study drugs.
• Are 3 months and 1 day (91 days) to 21 years old.
• Agree to practice abstinence or use effective barrier method of birth control if they are able to become pregnant.
• Have signed consent of parent or guardian if under 18 years of age.
• Are willing to undergo complete cardiac conduction evaluation at screening.
• For Step II, are South African participants from Step I that are virologically successful by Week 96 of the last study patient enrolled in their respective part of Step I.

Exclusion Criteria

• Have hepatitis.
• Have a serious infection that requires treatment at the time of study entry.
• Are allergic to atazanavir.
• Are receiving chemotherapy for cancer.
• Have any serious conditions (other than HIV infection) at study entry that might affect the results of the study.
• Are pregnant or breast-feeding.
• Show toxicity at study entry.
• Are receiving certain drugs or treatments.
• Are receiving pentamidine (by vein) for Pneumocystis carinii pneumonia within 3 months of study entry; ongoing monthly treatment with orally-inhaled pentamidine for prophylaxis is not excluded.
• Have a history of significant cardiac abnormalities or dysfunction.
• For Part II, virologic failure or the investigator deems discontinuation appropriate based on toxicity/tolerability.

Alabama
      Univ of Alabama at Birmingham - Pediatric, Birmingham,  Alabama,  35233,  United States; Recruiting
California
      UCSF / Moffitt Hosp - Pediatric, San Francisco,  California,  941430105,  United States; Recruiting
      Children's Hosp of Oakland, Oakland,  California,  946091809,  United States; Recruiting
      UCLA Med Ctr / Pediatric, Los Angeles,  California,  900951752,  United States; Recruiting
      Long Beach Memorial (Pediatric), Long Beach,  California,  90801,  United States; Recruiting
      UCLA Med Ctr, Los Angeles,  California,  90095,  United States; Recruiting
      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States; Recruiting
      Univ of California, San Diego, San Diego,  California,  92103,  United States; Recruiting
Colorado
      Children's Hosp of Denver, Denver,  Colorado,  80218-1088,  United States; Recruiting
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States; Recruiting
      Children's Hosp of Washington DC, Washington,  District of Columbia,  200102916,  United States; No longer recruiting
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States; Recruiting
      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States; No longer recruiting
Georgia
      The Med Ctr, Columbus,  Georgia,  31901,  United States; Recruiting
Illinois
      Cook County Hosp, Chicago,  Illinois,  60612,  United States; No longer recruiting
      Womens & Childrens HIV Program, Chicago,  Illinois,  60608-1797,  United States; Recruiting
Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States; Recruiting
Maryland
      Johns Hopkins Hosp - Pediatric, Baltimore,  Maryland,  212874933,  United States; Recruiting
Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States; Recruiting
      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States; Recruiting
      Univ of Massachusetts Med School, Worcester,  Massachusetts,  016550001,  United States; Recruiting
Mississippi
      Univ of Mississippi Med Ctr, Jackson,  Mississippi,  39213,  United States; No longer recruiting
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States; Recruiting
      UMDNJ - Robert Wood Johnson Med School / Pediatrics, New Brunswick,  New Jersey,  089030019,  United States; No longer recruiting
      Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl, Newark,  New Jersey,  07103,  United States; Recruiting
New York
      Harlem Hosp Ctr, New York,  New York,  10037,  United States; Recruiting
      Schneider Children's Hosp, New Hyde Park,  New York,  11040,  United States; No longer recruiting
      NYU/Belluvue Hospital, New York,  New York,  10016,  United States; Recruiting
      Bronx Municipal Hosp Ctr/Jacobi Med Ctr, Bronx,  New York,  10461,  United States; Recruiting
      Metropolitan Hosp Ctr, New York,  New York,  10029,  United States; No longer recruiting
      SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse,  New York,  13210,  United States; Recruiting
      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10457,  United States; Recruiting
      State Univ of New York at Stony Brook, Stony Brook,  New York,  117948111,  United States; Recruiting
      Univ of Rochester Med Ctr, Rochester,  New York,  146420001,  United States; No longer recruiting
      Montefiore Medical / AECOM, Bronx,  New York,  19461,  United States; Recruiting
      The Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States; Recruiting
North Carolina
      Duke Univ Med Ctr, Durham,  North Carolina,  277103499,  United States; No longer recruiting
Pennsylvania
      Children's Hosp of Philadelphia, Philadelphia,  Pennsylvania,  191044318,  United States; Recruiting
      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States; Recruiting
South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States; No longer recruiting
Tennessee
      Saint Jude Children's Research Hosp of Memphis, Memphis,  Tennessee,  381052794,  United States; Recruiting
Texas
      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States; Recruiting
Virginia
      Children's Hosp of the King's Daughters, Norfolk,  Virginia,  23507,  United States; Recruiting
Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States; No longer recruiting
Puerto Rico
      Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan,  009365067,  Puerto Rico; Recruiting
      Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon,  00956,  Puerto Rico; No longer recruiting

Study chairs or principal investigators

Richard Rutstein, MD,  Study Chair,  Children's Hospital of Philadelphia   
Grace Aldrovandi, MD,  Study Chair,  Children's Hospital Los Angeles   
Mark W Kline, MD,  Study Chair,  Baylor College of Medicine   

Study ID Numbers:  ACTG P1020-A; PACTG P1020-A
Record last reviewed:  January 2005
Last Updated:  April 7, 2005
Record first received:  December 6, 2000
ClinicalTrials.gov Identifier:  NCT00006604
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08