An International Study to Evaluate Recombinant Interleukin-2 in HIV Positive Patients Taking Anti-retroviral Therapy (ESPRIT)

• New or Recurrent HIV Disease Progression Event Including Death [ Time Frame: from randomization through study end - median of 7.6 years follow-up ] [ Designated as safety issue: Yes ]
  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
  
  

• New or Recurrent Serious HIV Disease Progression Event Including Death [ Time Frame: from randomization through study end - median of 7.6 years follow-up ] [ Designated as safety issue: Yes ]
  Patients with at least one: progressive multifocal leukoencephalopathy, lymphoma, visceral Kaposi's sarcoma, AIDS dementia complex, toxoplasmosis, histoplasmosis, cryptococcosis, Mycobacterium avium complex, wasting syndrome, and cytomegalovirus disease.
  
  
• Number of Participants Who Died From Any Cause [ Time Frame: from randomization through study end - median of 7.6 years follow-up ] [ Designated as safety issue: Yes ]
  
• Participants With a New Disease Progression Event or Death [ Time Frame: from randomization through 15 November 2008 - median of 7.6 years follow-up ] [ Designated as safety issue: Yes ]
  Includes first new episode of: CDC Category C 1993 AIDS-defining events plus 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
  
  
• Absolute CD4 Cell Counts Averaged Throughout Followup [ Time Frame: from randomization through study end - median of 7.6 years follow-up ] [ Designated as safety issue: Yes ]
  Average of all available CD4+ cell counts measured at follow-up visits
  
  
• Plasma HIV RNA Levels [ Time Frame: From randomization through study end - median of 7.6 years follow-up ] [ Designated as safety issue: No ]
  log10 HIV-RNA averaged throughout follow-up
  
  
• Number of Participants With Changes in Anti-retroviral Treatment (ART) [ Time Frame: From randomization through study end - median of 7.6 years follow-up ] [ Designated as safety issue: No ]
  Number of participants who changed ART at least once during the study period.
  
  
• Grade 4 Signs and Symptoms [ Time Frame: From randomization through study end - median of 7.6 years follow-up ] [ Designated as safety issue: Yes ]
  Participants with at least one grade 4 sign or symptom (except those limited to a laboratory measurement), other than AIDS-defining conditions. Events were graded according to a standardized toxicity table. Events not specifically contained in the toxicity table were considered Grade 4 if they resulted in extreme limitation in activity or required significant medical intervention/therapy, hospitalization or hospice care. Grade 4 events by type are given under the adverse events section.
  
  
• Pattern of Use of Prophylaxis for Opportunistic Infections [ Time Frame: last followup visit - median of 7.6 years follow-up ] [ Designated as safety issue: No ]
  Number of participants using pneumocystis pneumonia (PCP) prophylaxis at the last attended followup visit.
  
  
• Hepatic, Metabolic, and Cardiac Conditions [ Time Frame: From randomization through study end - median of 7.6 years follow-up ] [ Designated as safety issue: Yes ]
  Number of participants experiencing a "serious non-AIDS" event defined as first serious cardiovascular, renal, or hepatic event, or non-AIDS malignancy.
  
  

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.