Interleukin-2 Plus Anti-HIV Therapy in HIV-Infected Children With Weakened Immune Systems
Condition: HIV Infections
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Diphtheria & Tetanus Toxoids & Acellular Pertussis Vaccine Adsorbed; Diphtheria and Tetanus Toxoids Adsorbed; Tetanus and Diphtheria Toxoids Adsorbed; Bacteriophage phi X 174; Aldesleukin
Intervention type(s): Biological; Biological; Biological; Drug; Drug
Intervention MeSH terms: Aldesleukin
Primary purpose: Treatment
Keywords: Injections, Subcutaneous; Interleukin-2; Dose-Response Relationship, Drug; Drug Therapy, Combination; Immunocompromised Host; CD4 Lymphocyte Count; Anti-HIV Agents