A Randomized, Open-Label, Phase III, International Study of Subcutaneous Recombinant IL-2 in Patients With HIV-1 Infection and CD4+ Cell Counts 300/mm^3 or Greater: Evaluation of Subcutaneous Proleukin in a Randomized International Trial
Overview
- Phase
- Phase 3
- Intervention
- Recombinant interleukin-2 (rIL-2)
- Conditions
- HIV Infections
- Sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)
- Enrollment
- 4150
- Locations
- 248
- Primary Endpoint
- New or Recurrent HIV Disease Progression Event Including Death
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to see if it is effective to give HIV positive patients recombinant interleukin-2 (rIL-2) in addition to anti-HIV therapy. Patients will be followed over a minimum of 4 years to study the long-term effects of rIL-2 on their HIV disease progression.
Anti-HIV therapy has been very successful in treating HIV positive patients and in keeping viral load (level of HIV in the blood) low. However, anti-HIV drugs cannot completely rid the body of the virus, and the immune system is never completely restored in HIV positive patients. Doctors hope that giving patients recombinant interleukin-2 (rIL-2) in addition to their anti-HIV therapy will help improve their immune systems and keep them healthier over a longer period of time. rIL-2 is a hormone naturally produced by the body during an immune response to a microbial infection.
Detailed Description
Much progress has been made in implementing potent antiretroviral therapy that is able to maximally suppress viral replication. However, these drug combinations do not result in viral eradication and, for many patients, virologic and immunologic control cannot be maintained. Even among patients with apparent virologic control, a "ceiling effect" seems to exist with failure of CD4 cell counts to rise on average more than 100 to 150 cells/mm\^3, at least during the first 2 years of therapy. The incomplete recovery of immune function after initiation of therapy remains an obstacle in the management of HIV. Preservation of immune function by direct expansion of CD4 lymphocytes with rIL-2 could represent a significant additional treatment strategy. It also has been speculated recently that rIL-2 in combination with potent antiretroviral therapy may be a useful approach for purging HIV from the latently infected CD4 cells. It is hoped that intervention with rIL-2 therapy in combination with antiretroviral therapy at an early stage of HIV infection can prevent CD4 T-cell depletion and result in fewer AIDS-defining illnesses than with antiretroviral therapy alone. Patients are randomized to receive subcutaneous (SC) rIL-2 therapy or no rIL-2 therapy. All patients must be taking a regimen of combination antiretroviral treatment, with the choice of therapy at the discretion of the treating clinician. Antiretroviral medications are not provided by this study. Recombinant IL-2 is given SC for 5 consecutive days every 8 weeks for at least 3 cycles unless toxicities or other contraindications develop. After the first three cycles, additional cycles are given at the discretion of each patient's physician, with a general goal of maintaining the patient's CD4 cell count at twice the baseline level or at 1,000 cells/mm\^3 or above for as long as possible. Patients in the no rIL-2 group receive no injections. Patients in both treatment groups are seen every 4 months for follow-up data collection to monitor viral load and CD4 cell counts. All patients are followed for a minimum of 4 years. During the trial, patients in the no SC rIL-2 group are not given rIL-2 at any point. However, at the end of the study, if rIL-2 is found to be effective in reducing the rate of disease progression \[AS PER AMENDMENT 12/15/00: (new and recurrent events)\], including death, all patients are offered rIL-2.
Investigators
Eligibility Criteria
Inclusion Criteria
- •HIV positive
- •Have a CD4 cell count of 300 cells/mm3 or more within 45 days of study entry
- •Are on combination anti-HIV therapy or are beginning anti-HIV therapy at the time of study entry
- •Are at least 18 years old
Exclusion Criteria
- •Have received IL-2 before
- •Have cancer requiring chemotherapy
- •Have evidence of active clinical disease within the past year for any AIDS-defining illness or certain other conditions such as herpes zoster or Chagas disease. (This study has been changed. Previously, patients were ineligible if they had a history of any AIDS-defining illness or certain other conditions.)
- •Have used certain medications, such as corticosteroids or drugs affecting the immune system, in the 45 days before study entry
- •Have a nervous system disorder requiring antiseizure medication
- •Have an autoimmune or inflammatory disease such as inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), psoriasis, optic neuritis, or any autoimmune/inflammatory diseases with potentially life-threatening complications
- •Are pregnant or breastfeeding
Arms & Interventions
rIL-2
Recombinant interleukin-2 (rIL-2) therapy used with combination anti-HIV medication of choice.
Intervention: Recombinant interleukin-2 (rIL-2)
Outcomes
Primary Outcomes
New or Recurrent HIV Disease Progression Event Including Death
Time Frame: from randomization through study end - median of 7.6 years follow-up
Participants who die or experience at least one: any CDC Category C 1993 AIDS-defining events or one of the following: invasive aspergillosis, bartonellosis, Chagas disease, Herpes zoster, visceral Leishmaniasis, Hodgkin's lymphoma, non-Hodgkin's lymphoma (all cell types), microsporidiosis, nocardiosis, disseminated Penicillium marneffii, extrapulmonary Pneumocystis carinii, and Rhodococcus equi disease
Secondary Outcomes
- New or Recurrent Serious HIV Disease Progression Event Including Death(from randomization through study end - median of 7.6 years follow-up)
- Number of Participants Who Died From Any Cause(from randomization through study end - median of 7.6 years follow-up)
- Participants With a New Disease Progression Event or Death(from randomization through 15 November 2008 - median of 7.6 years follow-up)
- Absolute CD4 Cell Counts Averaged Throughout Followup(from randomization through study end - median of 7.6 years follow-up)
- Plasma HIV RNA Levels(From randomization through study end - median of 7.6 years follow-up)
- Number of Participants With Changes in Anti-retroviral Treatment (ART)(From randomization through study end - median of 7.6 years follow-up)
- Grade 4 Signs and Symptoms(From randomization through study end - median of 7.6 years follow-up)
- Pattern of Use of Prophylaxis for Opportunistic Infections(last followup visit - median of 7.6 years follow-up)
- Hepatic, Metabolic, and Cardiac Conditions(From randomization through study end - median of 7.6 years follow-up)