The purpose of this study is to see if it is effective to give HIV-positive patients interleukin-2 (rIL-2) in addition to anti-HIV therapy. Patients will be followed over a period of 5 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 rIL-2 plus anti-HIV therapy will help improve their immune systems and keep them healthier over a longer period of time. IL-2 is a protein found naturally in the blood that helps boost the immune system.

Condition	Treatment or Intervention	Phase
HIV Infections	Drug: Aldesleukin	Phase III

Further Study Details: 

Expected Total Enrollment:  4000

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/mm3, 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 IL-2 could represent a significant additional treatment strategy. It also has been speculated recently that IL-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 SC rIL-2 therapy or no SC rIL-2 therapy. All patients must receive combination antiretroviral treatment, with the choice of therapy at the discretion of the treating clinician. However, 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/mm3 or above for as long as possible. Patients in the no SC 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 an average of 5 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.

Ages Eligible for Study:  18 Years and above,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria

Patients may be eligible for this study if they:

• Are 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

Patients will not be eligible for this study if they:

• 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 breast-feeding.

California
      West Los Angeles VAMC, Los Angeles,  California,  90073,  United States
Colorado
      Univ Hosp Infectious Disease Clinic, Denver,  Colorado,  80204-4507,  United States
District of Columbia
      Whitman Walker Clinic, Washington,  District of Columbia,  20009,  United States
      Washington DC VA Medical Center, Washington,  District of Columbia,  20422,  United States
      George Washington Univ Med Ctr, Washington,  District of Columbia,  20037,  United States
Florida
      Miami Veterans Administration Med Ctr, Miami,  Florida,  33125,  United States
Georgia
      Atlanta VA Med Ctr, Decatur,  Georgia,  30033,  United States
Illinois
      AIDS Research Alliance - Chicago, Chicago,  Illinois,  60657,  United States
      VA Chicago Health Care System - West Side Div, Chicago,  Illinois,  60612,  United States
Maryland
      Natl Naval Med Ctr, Bethesda,  Maryland,  208995000,  United States
      Warren G Magnuson Clinical Ctr, Bethesda,  Maryland,  208924754,  United States
Michigan
      William Beaumont Hosp, Royal Oak,  Michigan,  48073,  United States
Minnesota
      Mayo Clinic, Rochester,  Minnesota,  55905,  United States
      Abbott-Northwestern Hosp / Clinic 42, Minneapolis,  Minnesota,  55404,  United States
New Jersey
      Infectious Disease Specialists of NJ, Union,  New Jersey,  07083,  United States
New York
      Columbia University, New York,  New York,  10032,  United States
Oregon
      Research & Education Group, Portland,  Oregon,  97209,  United States
Texas
      Houston Veterans Administration Med Ctr, Houston,  Texas,  77030,  United States
      Univ TX Health Science Ctr, Houston,  Texas,  77030,  United States
      South Texas Veterans Health Care System, San Antonio,  Texas,  78284,  United States
      Montrose Clinic, Houston,  Texas,  77006,  United States
Argentina
      Hosp Gen de Agudos Juan A Fernandez, Buenos Aires,  Argentina
Australia
      Royal Perth Hosp, Perth,  Australia
      Prahran Market Clinic, South Yarra,  Australia
      Holdsworth House General Practice, Darlinghurst,  Australia
      Carlton Clinic, Carlton,  Australia
      Marilyn McMurchie, MD, Darlinghurst,  Australia
      Queensland Health - AIDS Med Unit, Brisbane,  Australia
      Centre Clinic, St Kilda,  Australia
      Bourke Street Clinic, Surry Hills,  Australia
      Albion Street Clinic, Surry Hills,  Australia
      Burwood Street General Practice, Burwood,  Australia
      Gold Coast Sexual Health Clinic, Miami,  Australia
Belgium
      CHU Saint Pierre, Brussels,  Belgium
Canada
      Victoria Gen Hosp, QE II Health Sciences, Halifax,  Canada
Canada, Alberta
      Univ of Alberta/Division of Inf Dis/Dept of Med, Edmonton,  Alberta,  Canada
Canada, Ontario
      Toronto Gen Hosp, Toronto,  Ontario,  Canada
      McMaster Univ Med Centre, Hamilton,  Ontario,  Canada
      Windsor Regional Hosp, Windsor,  Ontario,  Canada
Canada, Quebec
      Montreal Chest Institute, Montreal,  Quebec,  Canada
      Centre Hospitalier Universitaire de Quebec, Ste Foy,  Quebec,  Canada
      Univ de Sherbrooke / Ctr de Recherche Clinique, Fleurimont,  Quebec,  Canada
Denmark
      Hvidovre Univ Hosp, Hvidore,  Denmark
      Odense Univ Hosp, Unknown,  Denmark
      Marselisborg Hosp, Aarus C,  Denmark
      Rigohospitalet / Dept of Infectious Diseases, Copenhagen,  Denmark
      Aalborg Hosp South, Aalborg,  Denmark
France
      Hopital Bichat - Claude Bernard, Paris,  France
      Hosp Saint-Louis, Paris Cedex IO,  France
      Centre Hosp de la Region Annecienne, ANNECY Cedex,  France
Germany
      Klinikum Der Johann Wolfgang Goethe Universitat, Frankfurt,  Germany
      Univ of Wuerzburg, Wuerzburg,  Germany
      Haven Program, Laurentian Hosp, Sudburg,  Germany
      Klinik I fir Innere Medizin der Univ zu Koln, Koln,  Germany
      Ruhr Univ, Bochum, Bochum,  Germany
      Klinikum Innenstadt, Munchen,  Germany
Ireland
      Royal Victoria Hosp, Belfast,  Ireland
Israel
      Kaplan Med Ctr, Rehovot,  Israel
Italy
      Ospedale S Raffaele, Milano,  Italy
      Ospedale Luigi Sacco Cargnel, Milano,  Italy
      Universita degli Studi di Modena e Reggio Emilia, Modena,  Italy
Japan
      International Med Ctr of Japan, Tokyo,  Japan
      Univ of Tokyo Institute of Medical Science, Tokyo,  Japan
      Osaka National Hosp, Osaka,  Japan
Morocco
      Univ Hosp Ctr of the Med School, Casablanca,  Morocco
Netherlands
      Kennemer Gasthuis, Lokatie EG, AK Harlem,  Netherlands
      St Elisabeth Zeikenhuis, Tilburg,  Netherlands
      Stichting Medisch Centrum Jan van Goyen, Amsterdam,  Netherlands
Norway
      Ulleval Hosp, Oslo,  Norway
Portugal
      Hosp De Santa Maria, Lisboa,  Portugal
Spain
      Hosp La Paz, Madrid,  Spain
      Hosp De Mostoles, Madrid,  Spain
      Hosp Carlos III, Madrid,  Spain
      Hosp Doce De Octubre, Madrid,  Spain
      Hosp Univ Germans Trias i Pujol, Barcelona,  Spain
      Hosp Universitario Morales Meseguer, Murcia,  Spain
      Hosp Juan Ramon Jimenez, Huelva,  Spain
      Hosp Ramon y Cajal, Madris,  Spain
      Hosp Univ San Carlos, Madrid,  Spain
      Hosp de la Princesa, Madrid,  Spain
      Hosp Central de Asturias, Asturias,  Spain
      Hosp Nuestra Sra De Aranzazu, Guipuzcoa,  Spain
      Hosp del Mar, Barcelona,  Spain
      Hosp Juan Canalejo, A Coruna,  Spain
Sweden
      Venhalsan Soder Hosp, Stockholm,  Sweden
Thailand
      Chulalongkorn Univ Hosp, Pathumwan,  Thailand
      Chonburi Reg Hosp, Chonburi,  Thailand
      Chiangrai Reg Hosp, Chiangrai,  Thailand
United Kingdom
      Saint Mary's Hosp, London,  United Kingdom
      Royal Free Hosp, London,  United Kingdom
      Royal Sussex County Hosp, Brighton,  United Kingdom
      Chelsea and Westminster Hosp, London,  United Kingdom
      Gartnaval Gen Hosp, Glasgow,  United Kingdom
      Western Gen Hosp, Edinburgh,  United Kingdom
      Peterborough District Hosp, Cambridgeshire,  United Kingdom
      St Bartholomews Hosp, London,  United Kingdom
      Univ College London Med School, London,  United Kingdom
      King's College Hosp, Cambewell,  United Kingdom
      General Infirmary at Leeds, Leeds,  United Kingdom
      North Manchester Gen Hosp, Manchester,  United Kingdom

Study chairs or principal investigators

Donald Abrams,  Study Chair
David Cooper,  Study Chair

Study ID Numbers:  ESPRIT 001; 00 I-0071
Record last reviewed:  February 2005
Last Updated:  April 7, 2005
Record first received:  March 10, 2000
ClinicalTrials.gov Identifier:  NCT00004978
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-04-08