The purpose of this study is to determine the safety of a drug called interleukin-2 (IL-2) given with anti-HIV therapy in children with HIV infection. This study will also determine the best dose of IL-2 to give children. IL-2 is an important substance produced by the body's white blood cells that helps the body fight infection. People with HIV infection do not produce enough IL-2. It is hoped that IL-2 treatment will help boost the immune system in people with HIV infection. It has not been studied very much in children and doctors need to know what doses are safe to give.

Condition	Treatment or Intervention	Phase
HIV Infections	Vaccine: Diphtheria & Tetanus Toxoids & Acellular Pertussis Vaccine Adsorbed  Vaccine: Diphtheria and Tetanus Toxoids Adsorbed  Vaccine: Tetanus and Diphtheria Toxoids Adsorbed  Drug: Bacteriophage phi X 174  Drug: Aldesleukin	Phase I

Further Study Details: 

Expected Total Enrollment:  84

One of the challenges in effective combination therapy in HIV-infected patients is the ability to achieve immune reconstitution. IL-2 is hypothesized to restore and/or preserve the immune system when added to potent antiretroviral regimens. This study will evaluate restoration of immune functions of CD4 cells and will also determine the best way to deliver IL-2 in a safe and effective way.

Part I: Patients add a 5-day course of subcutaneous IL-2 every 8 weeks for up to 48 weeks (6 cycles) to their HAART therapy. Three dose levels of IL-2 are administered. [AS PER AMENDMENT 5/3/01: It is strongly recommended, but not required, that] the first and second cycles of IL-2 are given in the hospital on an inpatient basis. The parent or patient is trained to give the injections and has the option of administering subsequent injections at home. Patients are monitored for CD4 and CD8 cell count and viral load. Enrollment into Part 1 begins at the lowest dose level; assuming no serious toxicities (Grade 3 or higher) occur, patients are enrolled into higher dose levels. The highest tolerated dose is established. Part 2: After the highest tolerated dose is established in Part 1, additional patients are randomized to receive HAART alone (Arm 1), HAART with high-dose IL-2 (Arm 2), or HAART with low-dose IL-2 (Arm 3). High-dose IL-2 is given twice daily at the highest dose tolerated in Part 1 for 5 days every 8 weeks for 6 cycles. Low-dose IL-2 is given once a day every day for 48 weeks. For Arms 2 and 3 [AS PER AMENDMENT 5/3/01: (except patients in the pharmacokinetic substudy), it is strongly recommended, but not required, that] IL-2 is given the first week on an inpatient basis by hospital personnel. As in Part 1, there is the option of administering the remaining injections at home. Intensive toxicity monitoring, routine lymphocyte subsets, and quantitative HIV RNA are performed on all patients at specified time points during the study. The first 12 patients in Arms 2 and 3 have pharmacokinetic testing with frequent blood samples drawn at intervals, some of which require staying up to 12 hours at the clinic. Diphtheria/tetanus immunizations and bacteriophage phi X174 immunizations are administered to all patients to determine antibody responses.

Ages Eligible for Study:  2 Years   -   18 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

A child may be eligible for this trial if he/she:

• Is HIV-positive.
• Is 2 to 18 years old (consent of parent or guardian required if under 18).
• Has received 12 or more weeks of anti-HIV drug therapy, consisting of at least 3 drugs. This combination may include a nucleoside reverse transcriptase inhibitor (NRTI), a nonnucleoside reverse transcriptase inhibitor, or a protease inhibitor, or 3 NRTIs. Combinations of NRTIs may not include abacavir (ABC). Patients may have taken ABC if it was not in combination with 2 other NRTIs. (This reflects a change in the requirement for anti-HIV therapy.)
• Has a plasma HIV RNA level of less than 10,000 copies/ml.
• Has evidence of a weakened immune system (based on CD4 cell counts and absolute CD4 percentage less than 25 percent). (This reflects a change in how a weakened immune system is defined.)
• Has a parent or guardian who is willing to comply with study requirements.
• Has symptoms of HIV infection.

Exclusion Criteria

A child will not be eligible for this study if he/she:

• Has an active opportunistic (AIDS-related) infection.
• Is pregnant.
• Is taking certain medications, such as steroids or other drugs that affect the immune system, within 6 weeks prior to study entry.
• Is taking ABC.
• Is taking certain antibodies.
• (Exclusion criteria reflect changes.)

California
      UCSF / Moffitt Hosp - Pediatric, San Francisco,  California,  941430105,  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
District of Columbia
      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States
      Children's National Med Ctr, Washington,  District of Columbia,  20010-2970,  United States
Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States
      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States
      University of South Flordia, St. Petersburg,  Florida,  33701,  United States
Illinois
      Chicago Children's Memorial Hosp, Chicago,  Illinois,  606143394,  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
New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States
      Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl, Newark,  New Jersey,  07103,  United States
New York
      North Shore Univ Hosp, Great Neck,  New York,  11021,  United States
      Schneider Children's Hosp, New Hyde Park,  New York,  11040,  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
      Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York,  New York,  10032,  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

Savita Pahwa,  Study Chair

Study ID Numbers:  ACTG 402; PACTG 402
Record last reviewed:  February 2005
Last Updated:  April 7, 2005
Record first received:  July 14, 2000
ClinicalTrials.gov Identifier:  NCT00006066
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08