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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Recombinant interleukin-2 (rIL-2)

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.

• Study Type: Interventional
• Enrollment (Actual): 4150
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Cordoba, Argentina, 5000
    • Hosp. Rawson CRS
  • La Plata, Argentina, 1900
    • Hosp. Interzonal de Agudos San Juan de Dios CRS
  • Mendoza, Argentina, 5500
    • Hosp. Central, Immunology Dept. CRS
  • Buenos Aires
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, 1020
      • Hosp. de Clinicas Jose de San Martin, Div. Infectologia CRS
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, 1199
      • Hosp. Italiano de Buenos Aires, Infectious Diseases Section CRS
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, 1221
      • Hosp. Gen. de Agudos JM Ramos Mejia, Servicio de Inmunocomprometidos CRS
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, 1282
      • Hospital de Infecciosas F.J. Muniz CRS
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, 1425
      • Funcei Crs
    • Ciudad de Buenos Aires, Buenos Aires, Argentina, 1425
      • Hosp. Gen. de Agudos Juan A. Fernandez CRS
    • Ciudad de Buenos Aires, Buenos Aires, Argentina
      • Hosp. Gen. de Agudos 'Teodoro Alvarez' CRS
    • El Palomar, Buenos Aires, Argentina, 1706
      • Hospital Nacional Professor Alejandro Posadas CRS
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Hospital Interzonal de Agudos Oscar Alende, Sala de Infectologia CRS
  • Provincia De Santa Fe
    • Rosario, Provincia De Santa Fe, Argentina, 2000
      • Caici Crs
• Australia
  • Miami, Queensland, Australia
    • Gold Coast Sexual Health Clinic CRS
  • Australian Capital Territory
    • Canberra, Australian Capital Territory, Australia, 2601
      • Interchange General Practice CRS
    • Woden, Australian Capital Territory, Australia, 2606
      • Canberra Hosp., Canberra Sexual Health Clinic CRS
  • New South Wales
    • Burwood, New South Wales, Australia, 2134
      • Burwood Road Gen. Practice CRS
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincent's Hospital CRS
    • Darlinghurst, New South Wales, Australia, 2010
      • Taylor Square Private Clinic CRS
    • Darlinghurst, New South Wales, Australia
      • Holdsworth House Gen. Practice CRS
    • Newcastle, New South Wales, Australia, 2305
      • John Hunter Hosp., Immunology & Infectious Diseases Unit CRS
    • Surry Hills, New South Wales, Australia, 2010
      • 407 Doctors CRS
    • Surry Hills, New South Wales, Australia
      • Albion Street Ctr. CRS
  • Queensland
    • Brisbane, Queensland, Australia
      • Queensland Health - AIDS Med. Unit CRS
    • Cairns, Queensland, Australia, 4870
      • Cairns Base Hosp., Sexual Health Services CRS
    • Highgate Hill, Queensland, Australia, 4101
      • Gladstone Road Medical Ctr. CRS
    • Nambour, Queensland, Australia, 4560
      • Nambour Gen. Hosp. CRS
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hosp. CRS
    • Adelaide, South Australia, Australia, 5000
      • The Care & Prevention Programme CRS
  • Victoria
    • Carlton, Victoria, Australia
      • Carlton Clinic CRS
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hosp., Clinical Research - Infectious Diseases Unit CRS
    • Melbourne, Victoria, Australia
      • Prahran Market Clinic CRS
    • Northcote, Victoria, Australia, 3070
      • Northcote Clinic CRS
    • Parkville, Victoria, Australia, 3052
      • Royal Melbourne Hosp., Victorian Infectious Diseases Service CRS
    • St. Kilda, Victoria, Australia
      • The Ctr. Clinic INSIGHT CRS
  • Western Australia
    • Perth, Western Australia, Australia
      • Royal Perth Hospital CRS
• Austria
  • Vienna, Austria, A-1090
    • Univ. of Vienna Med. School, Div. of Allergy, Immunology & Infectious Diseases - Sued B CRS
  • Wien, Austria, A-1140
    • SMZ Baumgartner Hoehe, Immunambulanz Pavillion Wienerwald Parterre CRS
• Belgium
  • Bruxelles, Belgium
    • Ctr. Hospitalier Universitaire, St Pierre, Div. of Infectious Diseases (PL5) CRS
• Brazil
  • Sao Paulo, Brazil, 01246-900
    • Instituto de Infectologia Emilio Ribas CRS
  • Sao Paulo, Brazil, 04040-002
    • Universidade Federal de Sao Paulo,IDIPA-Instituto Paulista de Doencas Infecciosas e Parasitarias CRS
  • Sao Paulo
    • Vila Mariana, Sao Paulo, Brazil, 04121-000
      • Centro de Referencia e Treinamento em DST/AIDS - Sao Paulo CRS
• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • Univ. of Alberta Hosp., Clinical Research Office CRS
  • British Columbia
    • Victoria, British Columbia, Canada
      • Cool Aid Community Health Ctr. CRS
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Q.E. II Health Sciences Ctr., Captial District Authority, Victoria Gen. Hosp. CRS
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster Univ. Med. Ctr. Hamiton Health Sciences, SIS Clinic CRS
    • London, Ontario, Canada, N5Y 3H6
      • St. Joseph's Health Ctr. of London, HIV Care Programme CRS
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hosp., Gen. Campus CRS
    • Sudbury, Ontario, Canada, P3E 5J1
      • The HAVEN Program, Sudbury Regional Hosp., Laurentian Site CRS
    • Toronto, Ontario, Canada
      • Toronto Gen. Hosp. Infectious Diseases CRS
    • Windsor, Ontario, Canada
      • Windsor Regional Hosp., HIV Care Program CRS
  • Quebec
    • Fleurimont, Quebec, Canada, J1H 5N4
      • CHUS - Hopital Fleurimont, Centre de Recherche Clinique CRS
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneuve-Rosemont, Dept. de Microbiologie CRS
    • Montreal, Quebec, Canada, H2L 4M1
      • CHUM - Campus Notre-Dame CRS
    • Montreal, Quebec, Canada
      • Royal Victoria Hosp., Montreal Chest Institute CRS
    • Sainte-Foy, Quebec, Canada
      • Centre Hospitalier Universitaire de Quebec - CHUL, Centre de Recherche en Indectiologie CRS
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Royal Univ. Hosp. CRS
• Denmark
  • Aalborg, Denmark
    • Aalborg Hosp., Dept. of Infectious Diseases CRS
  • Aarhus, Denmark, DK-8200
    • Skejby Sygehus, Department of Infectious Diseases Q (ambulatoriet) CRS
  • Copenhagen, Denmark
    • Rigshospitalet, Department of Infectious Diseases, M5112 CRS
  • Hvidovre, Denmark
    • Hvidovre Univ. Hosp., Dept. of Infectious Diseases CRS
  • Odense, Denmark
    • Odense Univ. Hosp., Med. Dept. C CRS
• France
  • Angers, France, 49033
    • CHRU d'Angers, Service de Maladies Infectieuses CRS
  • Besancon, France, 25030
    • Hopital Saint-Jacques, Service des Maladies Infectieuses et Tropicales CRS
  • Bobigny, France, 93009
    • Hopital Avicenne, Service de Medecine B CRS
  • Clamart, France, 92141
    • Hopital Antoine Beclere Service d'Immunologie Clinique CRS
  • Colombes, France, 92701
    • Hopital Louis Mourier, Service de Medecine Interne CRS
  • Creteil, France, 94010
    • Hopital Henri Mondor, Immunopathologie Clinique CRS
  • Garches, France, 92380
    • Hopital Raymond Poincare - Vidal 2, Service des Maladies Infectieuses et Tropicales CRS
  • Le Kremlin-Bicetre, France, 94275
    • Hopital de Bicetre, Service de Medecine Interne CRS
  • Marseille, France, 13009
    • Hopital Sainte Marguerite, CISIH Hopital de Jour CRS
  • Marseille, France, 13385
    • Hopital de la Conception, Service des Maladies Infectieuses CRS
  • Montpellier, France, 34295
    • Hopital Gui de Chauliac, Service des Maladies Infectieuses et Tropicales CRS
  • Nice, France, 06202
    • Hopital de l'Archet 1, Service de Medecine Interne 2 Hematologie Clinique CRS
  • Paris, France, 75012
    • Hopital Saint-Antoine, Service de Maladies Infectieuses CRS
  • Paris, France, 75651
    • Hopital de La Salpetriere, Service de Medecine Interne CRS
  • Paris, France, 75674
    • Hopital Cochin, Service de Medecine Interne 2 CRS
  • Paris, France, 75743
    • Hopital Necker, Service des Maladies Infectieuses CRS
  • Paris, France, 75908
    • Hopital Europeen Georges Pompidou, Service d'Immunologie Clinique CRS
  • Paris, France, 75970
    • Hopital Tenon, Service de Maladies Infectieuses et Tropicales CRS
  • Paris, France
    • C.H.U. Bichat - Claude Bernard Service des Maladies Infectieuses et Tropicales CRS
  • Strasbourg, France, 67091
    • CHRU de Strasbourg (France) CRS
  • Suresenes, France, 92151
    • Hopital Foch, Service de Medecine Interne CRS
  • Pringy
    • Cedex, Pringy, France
      • Centre Hospitalier de la Region Annecienne, Service des Maladie Infectieuses CRS
• Germany
  • Berlin, Germany, 13353
    • Univ. Hosp. Charite, Dept of Infectious Diseases CRS
  • Bochum, Germany
    • Ruhr-Univ., Interdiszipl. Immunolog. Ambulanz CRS
  • Bonn, Germany, 53105
    • Medizinische Universitaetsklinik - Bonn, Immunologische Ambulanz CRS
  • Duesseldorf, Germany, 40237
    • Ctr. for HIV & Hepatogastroenterology, HIV Specialised Practice (Private Practice) CRS
  • Frankfurt, Germany, 60590
    • Johann Wolfgang Goethe Univ. Hosp., Infektionsambulanz CRS
  • Hamburg, Germany
    • IPM Study Ctr. (Hamburg) CRS
  • Heidelberg, Germany, 69115
    • Univ. Hosp. Heidelberg, Dept. of Dermatology CRS
  • Koln, Germany
    • Klinik I fur Innere Medizin der Universitat zu Koln, Studienburo fur Infektiologie u. HIV CRS
  • Munchen, Germany
    • Klinikum Innenstadt, Infektionsambulanz und Tagesklinik CRS
  • Wuerzburg, Germany
    • Univ. of Wuerzburg, Medizinische Poliklinik, Schwerpunkt Hepatologie/Infektiologie CRS
• Ireland
  • Dublin, Ireland
    • St. James' Hosp., Guide Clinic CRS
• Israel
  • Haifa, Israel, 31096
    • Rambam Med. Ctr., Immunology, Allergy & AIDS Institute, B. Rappaport Faculty of Medicine, Technion
  • Rehovot, Israel
    • Kaplan Med. Ctr., Ben Ari Institute of Clinical Immunology CRS
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Med. Ctr., Clinical Immunology Unit and AIDS Ctr. CRS
• Italy
  • Brescia, Italy, 25123
    • Civili di Brescia, 1st Division of Infectious Diseases CRS
  • Brescia, Italy, 25123
    • Civili di Brescia, Dept of Infectious & Tropical Disease, Hosp.Spedali Civili of Brescia CRS
  • Firenze, Italy, 50011
    • Ospedale S. Maria Annunziata, U.O. Malattie Infettive CRS
  • Milano, Italy
    • Ospedale San Raffaele, Centro San Luigi - Divisione Malattie Infettive CRS
  • Milano, Italy
    • Univ. of Milan, Ospedale Luigi Sacco, Institute of Infectious and Tropical Diseases CRS
  • Modena, Italy
    • Universita degli Studi di Modena e Reggio Emilia, Clinica delle Malattie Infettive e Tropicali CRS
  • Pavia, Italy, 27100
    • San Matteo Hospital - University of Pavia, Division of Infectious and Tropical Diseases CRS
  • Roma, Italy, 00185
    • Universita La Sapienza, Clinica Universita La Sapienza CRS
• Japan
  • Osaka, Japan
    • Osaka National Hosp. AIDS Ctr., Clinical Research Institute CRS
  • Tokyo, Japan
    • International Med. Ctr. of Japan CRS
  • Tokyo, Japan
    • Univ. of Tokyo, Research Hosp. of the Institute of Medical Science CRS
• Morocco
  • Casablanca, Morocco
    • Univ. Hosp. Ctr. of the Med. School of Casablanca, Infectious Diseases Unit CRS
• Netherlands
  • Amsterdam, Netherlands, 1017 JZ
    • OLVG -- locatie Prinsengracht, Dept. of Internal Medicine II CRS
  • Amsterdam, Netherlands, 1150 AZ
    • Academisch Medisch Centrum CRS
  • Amsterdam, Netherlands
    • Stichting Medisch Centrum Jan van Goyen, Dept. of Internal Medicine CRS
  • Groningen, Netherlands, 9713 GZ
    • Groningen Univ. Hosp., Department of Internal Medicine CRS
  • Haarlem, Netherlands
    • Kennemer Gasthuis, Lokatie EG CRS
  • Tilburg, Netherlands
    • St. Elisabeth Ziekenhuis CRS
• Norway
  • Oslo, Norway
    • Ulleval Hosp., Dept. of Infectious Diseases CRS
• Poland
  • Chorzow, Poland, 41-500
    • Szpital Specjalistyczny, Osrodek Diagnostyki i Terapii AIDS CRS
  • Szczecin, Poland, 71-455
    • Pomeranian Academy of Medicine (PAM), Dept. of Infectious Diseases and Hepatology CRS
  • Warsaw, Poland, 01-201
    • Wojewodzki Szpital Zakazny CRS
  • Wroclaw, Poland, 51-171
    • Wroclaw Univ., School of Med., Dept. of Infectious Diseases, Liver Diseases and AIDS CRS
• Portugal
  • Cascais, Portugal, 2775
    • Hospital de Cascais, HDDI, Departamento Medicina Interna CRS
  • Lisboa, Portugal, 1349-019
    • Hosp. de Egas Moniz, Servicio de Infecciologia e Medicina Tropical CRS
  • Lisboa, Portugal
    • Hosp. de Santa Maria, Servico de Doencas Infecciosas CRS
• Singapore
  • Singapore, Singapore, 308433
    • Tan Tock Seng Hosp., Infectious Diseases Research Ctr. CRS
• Spain
  • A Coruna, Spain
    • Hosp. Juan Canalejo, Dept. of Internal Medicine CRS
  • Barcelona, Spain, E-08025
    • Hosp. Santa Creu i Sant Pau, Servicio de Medicina Interna CRS
  • Barcelona, Spain, E-08036
    • Hosp. Clinico de Barcelona CRS
  • Barcelona, Spain
    • Hosp. del Mar, Internal Medicine-Infectious Diseases CRS
  • Barcelona, Spain
    • Hosp. Universitari Germans Trias i Pujol, HIV Unit and Retrovirology Lab. CRS
  • Madrid, Spain, E-28007
    • Hosp. Universitario Gregorio Maranion, Microbiology & Infectious Diseases Unit CRS
  • Madrid, Spain, E-28029
    • Centro de Investigacion Carlos III, Infectious Diseases Dept. CRS
  • Madrid, Spain, E-28911
    • Hosp. Severo Ochoa, Internal Medicine and Infectious Diseases CRS
  • Madrid, Spain
    • Hosp. 12 de Octubre, Pabellon de Medicina Communitaria CRS
  • Madrid, Spain
    • Hosp. Clinico San Carlos CRS
  • Madrid, Spain
    • Hosp. la Princesa, Internal Medicine and Infectious Diseases Service CRS
  • Madrid, Spain
    • Hosp. Ramon y Cajal (Madrid) CRS
  • Madrid, Spain
    • Hosp. Universitario La Paz CRS
  • Madrid, Spain
    • Hosp. Universitario Principe de Asturias CRS
  • Murcia, Spain
    • Hosp. Universitario Morales Meseguer CRS
  • Sevilla, Spain, E-41013
    • Hosp. Virgen del Rocio, Infectious Diseases Service CRS
  • Guipuzcoa
    • San Sebastian, Guipuzcoa, Spain, E-20011
      • Hosp. Donostia CRS
• Sweden
  • Stockholm, Sweden, SE-141 86
    • Karolinska Univ. Hosp. Huddinge, Dept. of Infectious Diseases CRS
  • Stockholm, Sweden
    • Venhalsan, Soder Hosp., Dept. of Infectious Diseases, Karolinska Univ. Hosp. CRS
• Switzerland
  • Ticino
    • Lugano, Ticino, Switzerland, CH-6903
      • Regional Hosp. of Lugano (Sede Civico), Ospedale Civico di Lugano, Infectious Diseases Unit CRS
• Thailand
  • Chiangrai, Thailand
    • Chiang Rai Regional Hosp. INSIGHT CRS
  • Chonburi, Thailand
    • Chonburi Regional Hosp., Dept. of Internal Medicine CRS
  • Khon Kaen, Thailand, 40002
    • Khon Kaen Univ., Srinagarind Hosp., Div. of Infectious Diseases & Tropical Medicine, Dept. of Medici
  • Ratchathewi
    • Bangkok, Ratchathewi, Thailand, 10700
      • Siriraj Hosp., Mahidol Univ. INSIGHT CRS
    • Bangkok, Ratchathewi, Thailand
      • Chulalongkorn Univ. Hosp., HIV-NAT Research Collaboration CRS
• United Kingdom
  • Birmingham, United Kingdom, B9 5ST
    • Heartlands Hosp. Dept. of Infection & Tropical Disease Outpatients CRS
  • Exeter, United Kingdom, EX1 2ED
    • Royal Devon & Exeter NHS Foundation Trust, Heavitree Hosp., Dept. of GU Medicine CRS
  • Leicester, United Kingdom, LE1 5WW
    • Leicester Royal Infirmary, Dept. of Infection & Tropical Medicine CRS
  • London, United Kingdom, E1 1BB
    • Royal London Hosp., Ambrose King Ctr. CRS
  • London, United Kingdom, SE1 7EH
    • St. Thomas' Hosp., Dept. of GU Medicine CRS
  • London, United Kingdom, SW17 0RE
    • St. George's Hosp. Clinical Infection UnitCRS
  • London, United Kingdom
    • Chelsea & Westminster Hosp., St. Stephens Ctr. CRS
  • London, United Kingdom
    • King's College Hosp., Caldecot Ctr. Dept. of Sexual Health CRS
  • London, United Kingdom
    • Royal Free Hosp., Dept. of Infection & Immunity, Ian Charleson Day Ctr. CRS
  • London, United Kingdom
    • St. Bartholomew's Hosp., Infection & Immunity Clinical Group CRS
  • London, United Kingdom
    • St. Mary's Hosp. of London, Imperial College School of Medicine CRS
  • London, United Kingdom
    • Univ. College London Med. School, Ctr. for Sexual Health & HIV Research CRS
  • Newcastle Upon Tyne, United Kingdom, NE4 6BE
    • Newcastle Gen. Hosp., Dept of Infection & Tropical Medicine CRS
  • Peterborough, United Kingdom
    • Edith Cavell Hosp. Dept. of Sexual Health, Clinic E CRS
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hosp., Dept. of GU Medicine Communicable Diseases Unit CRS
  • Brighton
    • Elm Grove, Brighton, United Kingdom, BN2 1ES
      • Brighton & Sussex Univ. Hosp. NHS Trust, HIV Research Office CRS
  • Northern Ireland
    • Belfast, Northern Ireland, United Kingdom
      • Royal Victoria Hosp. Dept. of Genitourinary Medicine CRS
  • Oxford
    • Headington, Oxford, United Kingdom, OX3 9DU
      • Churchill Hosp. John Warin Ward CRS
  • Scotland
    • Edinburgh, Scotland, United Kingdom
      • Western Gen. Hosp., Regional Infectious Diseases Unit CRS
    • Glasgow, Scotland, United Kingdom
      • Gartnaval Gen. Hosp., Brownlee Ctr. CRS
• United States
  • California
    • Los Angeles, California, United States, 90073
      • VA Greater Los Angeles Healthcare System, Infectious Diseases Section CRS
    • Mill Valley, California, United States, 94941-3013
      • Dr. M. Estes Med. Practice CRS
    • Oakland, California, United States, 94609
      • Dr. Robert Scott Med. Practice CRS
    • Oakland, California, United States, 94705
      • East Bay AIDS Ctr. CRS
    • San Francisco, California, United States, 94102
      • Dr. Shawn Hassler Med. Practice CRS
    • San Francisco, California, United States, 94114-1010
      • Dr. William Owen Med. Practice CRS
    • San Francisco, California, United States, 94114
      • Dr. Martin Mass Med. Practice CRS
    • San Francisco, California, United States, 94121
      • San Francisco VAMC, Infectious Diseases Clinic CRS
    • San Francisco, California, United States, 94143
      • UCSF PHP, Gen. Internal Medicine Practice CRS
    • San Francisco, California, United States, 94110-0242
      • Positive Health Program Clinic (San Francisco Gen. Hosp.) CRS
    • San Francisco, California, United States, 94110
      • Positive Health Practice West/ Dr. Steve Deeks CRS
    • San Francisco, California, United States, 94144
      • Castro-Mission Health Ctr. CRS
    • San Francisco, California, United States
      • Dr. Virginia Cafaro Med. Practice CRS
  • Colorado
    • Denver, Colorado, United States
      • Denver Public Health CRS
    • Denver, Colorado, United States, 80204-4507
      • Denver Infectious Diseases Consultants CRS
    • Denver, Colorado, United States
      • Univ. of Colorado Health Science Ctr. CRS
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS
    • Washington, District of Columbia, United States, 20009
      • Whitman-Walker Clinic CRS
    • Washington, District of Columbia, United States, 20037
      • George Washington Univ. Med. Ctr. Infectious Diseases - Clinical Trials Unit CRS
    • Washington, District of Columbia, United States, 20307
      • Walter Reed Army Med. Ctr., Infectious Disease Clinic CRS
    • Washington, District of Columbia, United States
      • Dr. Timothy A. Price Med. Practice CRS
  • Florida
    • Miami, Florida, United States, 33125
      • Miami VAMC CRS
    • Miami, Florida, United States, 33136
      • Univ. of Miami, Infectious Diseases Clinical Research Unit CRS
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • ARCA, Central Clinc CRS
    • Atlanta, Georgia, United States, 30308
      • Emory Univ. Crawford Long Hosp. CRS
    • Decatur, Georgia, United States, 30033
      • Atlanta VAMC CRS
  • Illinois
    • Chicago, Illinois, United States, 60610
      • Klein & Slotten Medical Associates CRS
    • Chicago, Illinois, United States, 60612
      • Univ. of Illinois Family Ctr. for Infectious Disease CRS
    • Chicago, Illinois, United States, 60657
      • Lakeshore Infectious Disease Associates CRS
    • Chicago, Illinois, United States, 60657
      • North Side Family Medicine CRS
    • Chicago, Illinois, United States, 60657
      • Northwestern Memorial Physicians Group CRS
    • Chicago, Illinois, United States, 60612
      • Jesse Brown VAMC CRS
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Med. Ctr. of Louisiana at New Orleans, HIV Outpatient Clinics CRS
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center, Louisiana Community AIDS Research Program(LaCARP) CRS
    • New Orleans, Louisiana, United States, 70146
      • New Orleans VAMC CRS
  • Maryland
    • Bethesda, Maryland, United States, 20814-9692
      • NIH Clinical Ctr., NIAID HIV Clinic CRS
    • Bethesda, Maryland, United States, 208995000
      • National Naval Med. Ctr., Infectious Diseases Special Immunology Clinic CRS
  • Michigan
    • Detroit, Michigan, United States
      • Henry Ford Hosp. CRS
    • Detroit, Michigan, United States
      • Wayne State Univ. CRS
    • Grosse Pointe Woods, Michigan, United States, 48236
      • St. John Hosp. & Med. Ctr., Infectious Diseases Dept. CRS
    • Royal Oak, Michigan, United States, 48073
      • William Beaumont Hosp., Infectious Disease Research CRS
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Abbott Northwestern Hosp., Clinic 42 CRS
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic INSIGHT CRS
  • New Jersey
    • Camden, New Jersey, United States, 07754
      • Cooper Univ. Hosp. CRS
    • Hillsborough, New Jersey, United States, 08844
      • ID Care Inc. - Hillsborough CRS
    • Neptune, New Jersey, United States, 07754
      • Jersey Shore Univ. Med. Ctr. CRS
    • Newark, New Jersey, United States, 07103
      • New Jersey Community Research Initiative, Jeffrey Bomser Clinic CRS
    • Newark, New Jersey, United States
      • Cathedral Healthcare System, St. Michael's Med. Ctr. CRS
    • Paterson, New Jersey, United States
      • St. Joseph's Hosp. & Med. Ctr. of New Jersey CRS
    • Perth Amboy, New Jersey, United States, 08861
      • Raritan Bay Med. Ctr., Perth Amboy Division CRS
    • Randolph, New Jersey, United States, 07869
      • ID Care - Randolph CRS
    • Union, New Jersey, United States, 07083
      • Infectious Disease Specialists of N.J., North Jersey Community Research Initiative CRS
    • Voorhees, New Jersey, United States, 08043
      • The Early Intervention Program at Kennedy Hosp. CRS
  • New York
    • Bronx, New York, United States, 10461
      • Jacobi Med. Ctr., Ambulatory Care Pavillion CRS
    • Bronx, New York, United States, 10468
      • Bronx VAMC CRS
    • New York, New York, United States, 10011
      • St. Vincent Hosp. & Med. Ctr. CRS
    • New York, New York, United States, 10037
      • Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Immune Deficiency Clinic of Portland CRS
    • Portland, Oregon, United States, 97204
      • Multnomah County Health Dept., HIV Health Services Ctr. CRS
    • Portland, Oregon, United States, 97213
      • Providence Portland Med. Ctr., Ambulatory Care and Education Ctr. CRS
    • Portland, Oregon, United States, 97201
      • Oregon Health & Sciences Univ. Internal Medicine (L-475) CRS
    • Portland, Oregon, United States, 97209
      • The Research & Education Group-Portland CRS
    • Portland, Oregon, United States, 97301
      • Legacy Clinic Emanuel CRS
    • Salem, Oregon, United States, 97301
      • Salem Hosp. CRS
    • Salem, Oregon, United States, 97305
      • Kaiser Permanente Lancaster Clinic CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple Univ. School of Medicine CRS
  • Texas
    • Houston, Texas, United States, 77030
      • Michael E. DeBakey VAMC CRS
    • Houston, Texas, United States, 77030
      • Thomas Street Clinic CRS
    • Houston, Texas, United States, 77030
      • Northwest Clinic CRS
    • Houston, Texas, United States, 77030
      • Univ. Clinical Research Ctr., Memorial Hermann Hosp. CRS
    • Houston, Texas, United States
      • Legacy Community Health Services, Inc., Montrose Clinic, Inc.
    • San Antonio, Texas, United States, 78284
      • South Texas Veterans Health Care System, Immunosuppression Clinic CRS
  • Virginia
    • Mechanicsville, Virginia, United States, 23116
      • Hanover Med. Park (Mechanicsville, VA) CRS
    • Portsmouth, Virginia, United States, 23708
      • Naval Med. Ctr. Portsmouth CRS
    • Richmond, Virginia, United States, 23224
      • CrossOver Health Ctr. CRS
    • Richmond, Virginia, United States, 23224
      • South Richmond Health Care Ctr. CRS
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VAMC CRS
    • Richmond, Virginia, United States
      • Virginia Commonwealth Univ. Medical Ctr. CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: rIL-2; Recombinant interleukin-2 (rIL-2) therapy used with combination anti-HIV medication of choice.	Drug: Recombinant interleukin-2 (rIL-2); Recombinant interleukin-2 at a dose of 7.5 MIU given twice daily subcutaneously for 5 consecutive days every 8 weeks for at least 3 cycles.; Other Names: Proleukin; Aldesleukin; IL-2
NO_INTERVENTION: No rIL-2; Control arm uses anti-HIV medication of choice without rIL-2.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New or Recurrent HIV Disease Progression Event Including Death	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	from randomization through study end - median of 7.6 years follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
New or Recurrent Serious HIV Disease Progression Event Including Death	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.	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	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	from randomization through 15 November 2008 - median of 7.6 years follow-up
Absolute CD4 Cell Counts Averaged Throughout Followup	Average of all available CD4+ cell counts measured at follow-up visits	from randomization through study end - median of 7.6 years follow-up
Plasma HIV RNA Levels	log10 HIV-RNA averaged throughout follow-up	From randomization through study end - median of 7.6 years follow-up
Number of Participants With Changes in Anti-retroviral Treatment (ART)	Number of participants who changed ART at least once during the study period.	From randomization through study end - median of 7.6 years follow-up
Grade 4 Signs and Symptoms	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.	From randomization through study end - median of 7.6 years follow-up
Pattern of Use of Prophylaxis for Opportunistic Infections	Number of participants using pneumocystis pneumonia (PCP) prophylaxis at the last attended followup visit.	last followup visit - median of 7.6 years follow-up
Hepatic, Metabolic, and Cardiac Conditions	Number of participants experiencing a "serious non-AIDS" event defined as first serious cardiovascular, renal, or hepatic event, or non-AIDS malignancy.	From randomization through study end - median of 7.6 years follow-up

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Chiron Corporation
• Investigators: Study Chair: Donald Abrams, MD, University of California, San Francisco; Study Chair: Marcelo Losso, MD, Hospital Jose Maria Ramos Mejia, Buenos Aires, Argentina

Publications and helpful links

General Publications

• Connors M, Kovacs JA, Krevat S, Gea-Banacloche JC, Sneller MC, Flanigan M, Metcalf JA, Walker RE, Falloon J, Baseler M, Feuerstein I, Masur H, Lane HC. HIV infection induces changes in CD4+ T-cell phenotype and depletions within the CD4+ T-cell repertoire that are not immediately restored by antiviral or immune-based therapies. Nat Med. 1997 May;3(5):533-40. doi: 10.1038/nm0597-533.
• Chun TW, Engel D, Mizell SB, Hallahan CW, Fischette M, Park S, Davey RT Jr, Dybul M, Kovacs JA, Metcalf JA, Mican JM, Berrey MM, Corey L, Lane HC, Fauci AS. Effect of interleukin-2 on the pool of latently infected, resting CD4+ T cells in HIV-1-infected patients receiving highly active anti-retroviral therapy. Nat Med. 1999 Jun;5(6):651-5. doi: 10.1038/9498.
• Emery S, Abrams DI, Cooper DA, Darbyshire JH, Lane HC, Lundgren JD, Neaton JD; ESPRIT Study Group. The evaluation of subcutaneous proleukin (interleukin-2) in a randomized international trial: rationale, design, and methods of ESPRIT. Control Clin Trials. 2002 Apr;23(2):198-220. doi: 10.1016/s0197-2456(01)00179-9.
• Arduino RC, Nannini EC, Rodriguez-Barradas M, Schrader S, Losso M, Ruxrungtham K, Allende MC, Emery S, Fosdick L, Neaton J, Tavel JA, Davey RT, Lane HC; Evaluation of Subcutaneous Proleukin in a Randomized International Trial (ESPRIT) Vanguard Group; ESPRIT Executive Committee. CD4 cell response to 3 doses of subcutaneous interleukin 2: meta-analysis of 3 Vanguard studies. Clin Infect Dis. 2004 Jul 1;39(1):115-22. doi: 10.1086/421775. Epub 2004 Jun 14.
• INSIGHT-ESPRIT Study Group; SILCAAT Scientific Committee; Abrams D, Levy Y, Losso MH, Babiker A, Collins G, Cooper DA, Darbyshire J, Emery S, Fox L, Gordin F, Lane HC, Lundgren JD, Mitsuyasu R, Neaton JD, Phillips A, Routy JP, Tambussi G, Wentworth D. Interleukin-2 therapy in patients with HIV infection. N Engl J Med. 2009 Oct 15;361(16):1548-59. doi: 10.1056/NEJMoa0903175.
• Larson GS, Carey C, Grarup J, Hudson F, Sachi K, Vjecha MJ, Gordin F; INSIGHT Group. Lessons learned: Infrastructure development and financial management for large, publicly funded, international trials. Clin Trials. 2016 Apr;13(2):127-36. doi: 10.1177/1740774515625974. Epub 2016 Feb 8.
• Nordell AD, McKenna M, Borges AH, Duprez D, Neuhaus J, Neaton JD; INSIGHT SMART, ESPRIT Study Groups; SILCAAT Scientific Committee. Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation. J Am Heart Assoc. 2014 May 28;3(3):e000844. doi: 10.1161/JAHA.114.000844.
• Mocroft A, Neuhaus J, Peters L, Ryom L, Bickel M, Grint D, Koirala J, Szymczak A, Lundgren J, Ross MJ, Wyatt CM; INSIGHT SMART Study Group; ESPRIT Study Group. Hepatitis B and C co-infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults. PLoS One. 2012;7(7):e40245. doi: 10.1371/journal.pone.0040245. Epub 2012 Jul 20.
• Pett SL, Carey C, Lin E, Wentworth D, Lazovski J, Miro JM, Gordin F, Angus B, Rodriguez-Barradas M, Rubio R, Tambussi G, Cooper DA, Emery S; INSIGHT-ESPRIT Study Group. Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT). HIV Med. 2011 Apr;12(4):219-27. doi: 10.1111/j.1468-1293.2010.00875.x. Epub 2010 Aug 31.

Helpful Links

• Click here for the ESPRIT International IL-2 Study for HIV-infected Persons Web Site

Study record dates

Study Major Dates

• Study Start: March 1, 2000
• Primary Completion (ACTUAL): November 1, 2008
• Study Completion (ACTUAL): November 1, 2008

Study Registration Dates

• First Submitted: March 10, 2000
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (ESTIMATE): August 31, 2001

Study Record Updates

• Last Update Posted (ACTUAL): November 5, 2021
• Last Update Submitted That Met QC Criteria: November 2, 2021
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; Anti-HIV Agents; HIV-1; CD4 Lymphocyte Count; Disease Progression; Recombinant Proteins; Interleukin-2; Follow-Up Studies; Injections, Subcutaneous
• Additional Relevant MeSH Terms: Infections; Physiological Effects of Drugs; Anti-Infective Agents; Peripheral Nervous System Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antineoplastic Agents; Aldesleukin; Interleukin-2
• Other Study ID Numbers: ESPRIT 001; 5U01AI046957 (NIH); 00 I-0071; 3U01AI046957-05S2 (NIH); 3U01AI046957-05S3 (NIH); 10118 (REGISTRY: DAIDS ES Registry Number)