Clinical trial NCT00004978: An International Study to Evaluate Recombinant Interleukin-2 in HIV Positive Patients Taking Anti-retroviral Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Keywords: Recombinant Proteins
Injections, Subcutaneous
HIV-1
Interleukin-2
Drug Therapy, Combination
CD4 Lymphocyte Count
Disease Progression
Follow-Up Studies
Anti-HIV Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Chiron Corporation
First posted: 2001-08-31
Enrollment: 4150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: New or Recurrent HIV Disease Progression Event Including Death
timeFrame: from randomization through study end - median of 7.6 years follow-up
Secondary outcomes:
measure: New or Recurrent Serious HIV Disease Progression Event Including Death
timeFrame: from randomization through study end - median of 7.6 years follow-up
measure: Number of Participants Who Died From Any Cause
timeFrame: from randomization through study end - median of 7.6 years follow-up
measure: Participants With a New Disease Progression Event or Death
timeFrame: from randomization through 15 November 2008 - median of 7.6 years follow-up
measure: Absolute CD4 Cell Counts Averaged Throughout Followup
timeFrame: from randomization through study end - median of 7.6 years follow-up
measure: Plasma HIV RNA Levels
timeFrame: From randomization through study end - median of 7.6 years follow-up
measure: Number of Participants With Changes in Anti-retroviral Treatment (ART)
timeFrame: From randomization through study end - median of 7.6 years follow-up
measure: Grade 4 Signs and Symptoms
timeFrame: From randomization through study end - median of 7.6 years follow-up
measure: Pattern of Use of Prophylaxis for Opportunistic Infections
timeFrame: last followup visit - median of 7.6 years follow-up
measure: Hepatic, Metabolic, and Cardiac Conditions
timeFrame: From randomization through study end - median of 7.6 years follow-up
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: VA Greater Los Angeles Healthcare System, Infectious Diseases Section CRS
state: California
city: Mill Valley
country: United States
facility: Dr. M. Estes Med. Practice CRS
state: California
city: Oakland
country: United States
facility: Dr. Robert Scott Med. Practice CRS
state: California
city: Oakland
country: United States
facility: East Bay AIDS Ctr. CRS
state: California
city: San Francisco
country: United States
facility: Dr. Shawn Hassler Med. Practice CRS
state: California
city: San Francisco
country: United States
facility: Positive Health Program Clinic (San Francisco Gen. Hosp.) CRS
state: California
city: San Francisco
country: United States
facility: Positive Health Practice West/ Dr. Steve Deeks CRS
state: California
city: San Francisco
country: United States
facility: Dr. William Owen Med. Practice CRS
state: California
city: San Francisco
country: United States
facility: Dr. Martin Mass Med. Practice CRS
state: California
city: San Francisco
country: United States
facility: San Francisco VAMC, Infectious Diseases Clinic CRS
state: California
city: San Francisco
country: United States
facility: UCSF PHP, Gen. Internal Medicine Practice CRS
state: California
city: San Francisco
country: United States
facility: Castro-Mission Health Ctr. CRS
state: California
city: San Francisco
country: United States
facility: Dr. Virginia Cafaro Med. Practice CRS
state: California
city: Denver
country: United States
facility: Denver Infectious Diseases Consultants CRS
state: Colorado
city: Denver
country: United States
facility: Denver Public Health CRS
state: Colorado
city: Denver
country: United States
facility: Univ. of Colorado Health Science Ctr. CRS
state: Colorado
city: Washington
country: United States
facility: Whitman-Walker Clinic CRS
state: District of Columbia
city: Washington
country: United States
facility: George Washington Univ. Med. Ctr. Infectious Diseases - Clinical Trials Unit CRS
state: District of Columbia
city: Washington
country: United States
facility: Walter Reed Army Med. Ctr., Infectious Disease Clinic CRS
state: District of Columbia
city: Washington
country: United States
facility: Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS
state: District of Columbia
city: Washington
country: United States
facility: Dr. Timothy A. Price Med. Practice CRS
state: District of Columbia
city: Miami
country: United States
facility: Miami VAMC CRS
state: Florida
city: Miami
country: United States
facility: Univ. of Miami, Infectious Diseases Clinical Research Unit CRS
state: Florida
city: Atlanta
country: United States
facility: ARCA, Central Clinc CRS
state: Georgia
city: Atlanta
country: United States
facility: Emory Univ. Crawford Long Hosp. CRS
state: Georgia
city: Decatur
country: United States
facility: Atlanta VAMC CRS
state: Georgia
city: Chicago
country: United States
facility: Klein & Slotten Medical Associates CRS
state: Illinois
city: Chicago
country: United States
facility: Jesse Brown VAMC CRS
state: Illinois
city: Chicago
country: United States
facility: Univ. of Illinois Family Ctr. for Infectious Disease CRS
state: Illinois
city: Chicago
country: United States
facility: Lakeshore Infectious Disease Associates CRS
state: Illinois
city: Chicago
country: United States
facility: North Side Family Medicine CRS
state: Illinois
city: Chicago
country: United States
facility: Northwestern Memorial Physicians Group CRS
state: Illinois
city: New Orleans
country: United States
facility: Med. Ctr. of Louisiana at New Orleans, HIV Outpatient Clinics CRS
state: Louisiana
city: New Orleans
country: United States
facility: Tulane University Health Sciences Center, Louisiana Community AIDS Research Program(LaCARP) CRS
state: Louisiana
city: New Orleans
country: United States
facility: New Orleans VAMC CRS
state: Louisiana
city: Bethesda
country: United States
facility: NIH Clinical Ctr., NIAID HIV Clinic CRS
state: Maryland
city: Bethesda
country: United States
facility: National Naval Med. Ctr., Infectious Diseases Special Immunology Clinic CRS
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Hosp. CRS
state: Michigan
city: Detroit
country: United States
facility: Wayne State Univ. CRS
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: St. John Hosp. & Med. Ctr., Infectious Diseases Dept. CRS
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hosp., Infectious Disease Research CRS
state: Michigan
city: Minneapolis
country: United States
facility: Abbott Northwestern Hosp., Clinic 42 CRS
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic INSIGHT CRS
state: Minnesota
city: Camden
country: United States
facility: Cooper Univ. Hosp. CRS
state: New Jersey
city: Hillsborough
country: United States
facility: ID Care Inc. - Hillsborough CRS
state: New Jersey
city: Neptune
country: United States
facility: Jersey Shore Univ. Med. Ctr. CRS
state: New Jersey
city: Newark
country: United States
facility: New Jersey Community Research Initiative, Jeffrey Bomser Clinic CRS
state: New Jersey
city: Newark
country: United States
facility: Cathedral Healthcare System, St. Michael's Med. Ctr. CRS
state: New Jersey
city: Paterson
country: United States
facility: St. Joseph's Hosp. & Med. Ctr. of New Jersey CRS
state: New Jersey
city: Perth Amboy
country: United States
facility: Raritan Bay Med. Ctr., Perth Amboy Division CRS
state: New Jersey
city: Randolph
country: United States
facility: ID Care - Randolph CRS
state: New Jersey
city: Union
country: United States
facility: Infectious Disease Specialists of N.J., North Jersey Community Research Initiative CRS
state: New Jersey
city: Voorhees
country: United States
facility: The Early Intervention Program at Kennedy Hosp. CRS
state: New Jersey
city: Bronx
country: United States
facility: Jacobi Med. Ctr., Ambulatory Care Pavillion CRS
state: New York
city: Bronx
country: United States
facility: Bronx VAMC CRS
state: New York
city: New York
country: United States
facility: St. Vincent Hosp. & Med. Ctr. CRS
state: New York
city: New York
country: United States
facility: Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)
state: New York
city: Portland
country: United States
facility: Oregon Health & Sciences Univ. Internal Medicine (L-475) CRS
state: Oregon
city: Portland
country: United States
facility: Multnomah County Health Dept., HIV Health Services Ctr. CRS
state: Oregon
city: Portland
country: United States
facility: The Research & Education Group-Portland CRS
state: Oregon
city: Portland
country: United States
facility: Providence Portland Med. Ctr., Ambulatory Care and Education Ctr. CRS
state: Oregon
city: Portland
country: United States
facility: Kaiser Immune Deficiency Clinic of Portland CRS
state: Oregon
city: Portland
country: United States
facility: Legacy Clinic Emanuel CRS
state: Oregon
city: Salem
country: United States
facility: Salem Hosp. CRS
state: Oregon
city: Salem
country: United States
facility: Kaiser Permanente Lancaster Clinic CRS
state: Oregon
city: Philadelphia
country: United States
facility: Temple Univ. School of Medicine CRS
state: Pennsylvania
city: Houston
country: United States
facility: Michael E. DeBakey VAMC CRS
state: Texas
city: Houston
country: United States
facility: Northwest Clinic CRS
state: Texas
city: Houston
country: United States
facility: Thomas Street Clinic CRS
state: Texas
city: Houston
country: United States
facility: Univ. Clinical Research Ctr., Memorial Hermann Hosp. CRS
state: Texas
city: Houston
country: United States
facility: Legacy Community Health Services, Inc., Montrose Clinic, Inc.
state: Texas
city: San Antonio
country: United States
facility: South Texas Veterans Health Care System, Immunosuppression Clinic CRS
state: Texas
city: Mechanicsville
country: United States
facility: Hanover Med. Park (Mechanicsville, VA) CRS
state: Virginia
city: Portsmouth
country: United States
facility: Naval Med. Ctr. Portsmouth CRS
state: Virginia
city: Richmond
country: United States
facility: CrossOver Health Ctr. CRS
state: Virginia
city: Richmond
country: United States
facility: South Richmond Health Care Ctr. CRS
state: Virginia
city: Richmond
country: United States
facility: Hunter Holmes McGuire VAMC CRS
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth Univ. Medical Ctr. CRS
state: Virginia
city: Ciudad de Buenos Aires
country: Argentina
facility: Hosp. de Clinicas Jose de San Martin, Div. Infectologia CRS
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: Hosp. Italiano de Buenos Aires, Infectious Diseases Section CRS
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: Hosp. Gen. de Agudos JM Ramos Mejia, Servicio de Inmunocomprometidos CRS
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: Hospital de Infecciosas F.J. Muniz CRS
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: Funcei Crs
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: Hosp. Gen. de Agudos Juan A. Fernandez CRS
state: Buenos Aires
city: Ciudad de Buenos Aires
country: Argentina
facility: Hosp. Gen. de Agudos 'Teodoro Alvarez' CRS
state: Buenos Aires
city: El Palomar
country: Argentina
facility: Hospital Nacional Professor Alejandro Posadas CRS
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: Hospital Interzonal de Agudos Oscar Alende, Sala de Infectologia CRS
state: Buenos Aires
city: Rosario
country: Argentina
facility: Caici Crs
state: Provincia De Santa Fe
city: Cordoba
country: Argentina
facility: Hosp. Rawson CRS
city: La Plata
country: Argentina
facility: Hosp. Interzonal de Agudos San Juan de Dios CRS
city: Mendoza
country: Argentina
facility: Hosp. Central, Immunology Dept. CRS
city: Canberra
country: Australia
facility: Interchange General Practice CRS
state: Australian Capital Territory
city: Woden
country: Australia
facility: Canberra Hosp., Canberra Sexual Health Clinic CRS
state: Australian Capital Territory
city: Burwood
country: Australia
facility: Burwood Road Gen. Practice CRS
state: New South Wales
city: Darlinghurst
country: Australia
facility: St. Vincent's Hospital CRS
state: New South Wales
city: Darlinghurst
country: Australia
facility: Taylor Square Private Clinic CRS
state: New South Wales
city: Darlinghurst
country: Australia
facility: Holdsworth House Gen. Practice CRS
state: New South Wales
city: Newcastle
country: Australia
facility: John Hunter Hosp., Immunology & Infectious Diseases Unit CRS
state: New South Wales
city: Surry Hills
country: Australia
facility: 407 Doctors CRS
state: New South Wales
city: Surry Hills
country: Australia
facility: Albion Street Ctr. CRS
state: New South Wales
city: Brisbane
country: Australia
facility: Queensland Health - AIDS Med. Unit CRS
state: Queensland
city: Cairns
country: Australia
facility: Cairns Base Hosp., Sexual Health Services CRS
state: Queensland
city: Highgate Hill
country: Australia
facility: Gladstone Road Medical Ctr. CRS
state: Queensland
city: Nambour
country: Australia
facility: Nambour Gen. Hosp. CRS
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hosp. CRS
state: South Australia
city: Adelaide
country: Australia
facility: The Care & Prevention Programme CRS
state: South Australia
city: Carlton
country: Australia
facility: Carlton Clinic CRS
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hosp., Clinical Research - Infectious Diseases Unit CRS
state: Victoria
city: Melbourne
country: Australia
facility: Prahran Market Clinic CRS
state: Victoria
city: Northcote
country: Australia
facility: Northcote Clinic CRS
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hosp., Victorian Infectious Diseases Service CRS
state: Victoria
city: St. Kilda
country: Australia
facility: The Ctr. Clinic INSIGHT CRS
state: Victoria
city: Perth
country: Australia
facility: Royal Perth Hospital CRS
state: Western Australia
city: Miami, Queensland
country: Australia
facility: Gold Coast Sexual Health Clinic CRS
city: Vienna
country: Austria
facility: Univ. of Vienna Med. School, Div. of Allergy, Immunology & Infectious Diseases - Sued B CRS
city: Wien
country: Austria
facility: SMZ Baumgartner Hoehe, Immunambulanz Pavillion Wienerwald Parterre CRS
city: Bruxelles
country: Belgium
facility: Ctr. Hospitalier Universitaire, St Pierre, Div. of Infectious Diseases (PL5) CRS
city: Vila Mariana
country: Brazil
facility: Centro de Referencia e Treinamento em DST/AIDS - Sao Paulo CRS
state: Sao Paulo
city: Sao Paulo
country: Brazil
facility: Instituto de Infectologia Emilio Ribas CRS
city: Sao Paulo
country: Brazil
facility: Universidade Federal de Sao Paulo,IDIPA-Instituto Paulista de Doencas Infecciosas e Parasitarias CRS
city: Edmonton
country: Canada
facility: Univ. of Alberta Hosp., Clinical Research Office CRS
state: Alberta
city: Victoria
country: Canada
facility: Cool Aid Community Health Ctr. CRS
state: British Columbia
city: Halifax
country: Canada
facility: Q.E. II Health Sciences Ctr., Captial District Authority, Victoria Gen. Hosp. CRS
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster Univ. Med. Ctr. Hamiton Health Sciences, SIS Clinic CRS
state: Ontario
city: London
country: Canada
facility: St. Joseph's Health Ctr. of London, HIV Care Programme CRS
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hosp., Gen. Campus CRS
state: Ontario
city: Sudbury
country: Canada
facility: The HAVEN Program, Sudbury Regional Hosp., Laurentian Site CRS
state: Ontario
city: Toronto
country: Canada
facility: Toronto Gen. Hosp. Infectious Diseases CRS
state: Ontario
city: Windsor
country: Canada
facility: Windsor Regional Hosp., HIV Care Program CRS
state: Ontario
city: Fleurimont
country: Canada
facility: CHUS - Hopital Fleurimont, Centre de Recherche Clinique CRS
state: Quebec
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont, Dept. de Microbiologie CRS
state: Quebec
city: Montreal
country: Canada
facility: CHUM - Campus Notre-Dame CRS
state: Quebec
city: Montreal
country: Canada
facility: Royal Victoria Hosp., Montreal Chest Institute CRS
state: Quebec
city: Sainte-Foy
country: Canada
facility: Centre Hospitalier Universitaire de Quebec - CHUL, Centre de Recherche en Indectiologie CRS
state: Quebec
city: Saskatoon
country: Canada
facility: Royal Univ. Hosp. CRS
state: Saskatchewan
city: Aalborg
country: Denmark
facility: Aalborg Hosp., Dept. of Infectious Diseases CRS
city: Aarhus
country: Denmark
facility: Skejby Sygehus, Department of Infectious Diseases Q (ambulatoriet) CRS
city: Copenhagen
country: Denmark
facility: Rigshospitalet, Department of Infectious Diseases, M5112 CRS
city: Hvidovre
country: Denmark
facility: Hvidovre Univ. Hosp., Dept. of Infectious Diseases CRS
city: Odense
country: Denmark
facility: Odense Univ. Hosp., Med. Dept. C CRS
city: Cedex
country: France
facility: Centre Hospitalier de la Region Annecienne, Service des Maladie Infectieuses CRS
state: Pringy
city: Angers
country: France
facility: CHRU d'Angers, Service de Maladies Infectieuses CRS
city: Besancon
country: France
facility: Hopital Saint-Jacques, Service des Maladies Infectieuses et Tropicales CRS
city: Bobigny
country: France
facility: Hopital Avicenne, Service de Medecine B CRS
city: Clamart
country: France
facility: Hopital Antoine Beclere Service d'Immunologie Clinique CRS
city: Colombes
country: France
facility: Hopital Louis Mourier, Service de Medecine Interne CRS
city: Creteil
country: France
facility: Hopital Henri Mondor, Immunopathologie Clinique CRS
city: Garches
country: France
facility: Hopital Raymond Poincare - Vidal 2, Service des Maladies Infectieuses et Tropicales CRS
city: Le Kremlin-Bicetre
country: France
facility: Hopital de Bicetre, Service de Medecine Interne CRS
city: Marseille
country: France
facility: Hopital Sainte Marguerite, CISIH Hopital de Jour CRS
city: Marseille
country: France
facility: Hopital de la Conception, Service des Maladies Infectieuses CRS
city: Montpellier
country: France
facility: Hopital Gui de Chauliac, Service des Maladies Infectieuses et Tropicales CRS
city: Nice
country: France
facility: Hopital de l'Archet 1, Service de Medecine Interne 2 Hematologie Clinique CRS
city: Paris
country: France
facility: Hopital Saint-Antoine, Service de Maladies Infectieuses CRS
city: Paris
country: France
facility: Hopital de La Salpetriere, Service de Medecine Interne CRS
city: Paris
country: France
facility: Hopital Cochin, Service de Medecine Interne 2 CRS
city: Paris
country: France
facility: Hopital Necker, Service des Maladies Infectieuses CRS
city: Paris
country: France
facility: Hopital Europeen Georges Pompidou, Service d'Immunologie Clinique CRS
city: Paris
country: France
facility: Hopital Tenon, Service de Maladies Infectieuses et Tropicales CRS
city: Paris
country: France
facility: C.H.U. Bichat - Claude Bernard Service des Maladies Infectieuses et Tropicales CRS
city: Strasbourg
country: France
facility: CHRU de Strasbourg (France) CRS
city: Suresenes
country: France
facility: Hopital Foch, Service de Medecine Interne CRS
city: Berlin
country: Germany
facility: Univ. Hosp. Charite, Dept of Infectious Diseases CRS
city: Bochum
country: Germany
facility: Ruhr-Univ., Interdiszipl. Immunolog. Ambulanz CRS
city: Bonn
country: Germany
facility: Medizinische Universitaetsklinik - Bonn, Immunologische Ambulanz CRS
city: Duesseldorf
country: Germany
facility: Ctr. for HIV & Hepatogastroenterology, HIV Specialised Practice (Private Practice) CRS
city: Frankfurt
country: Germany
facility: Johann Wolfgang Goethe Univ. Hosp., Infektionsambulanz CRS
city: Hamburg
country: Germany
facility: IPM Study Ctr. (Hamburg) CRS
city: Heidelberg
country: Germany
facility: Univ. Hosp. Heidelberg, Dept. of Dermatology CRS
city: Koln
country: Germany
facility: Klinik I fur Innere Medizin der Universitat zu Koln, Studienburo fur Infektiologie u. HIV CRS
city: Munchen
country: Germany
facility: Klinikum Innenstadt, Infektionsambulanz und Tagesklinik CRS
city: Wuerzburg
country: Germany
facility: Univ. of Wuerzburg, Medizinische Poliklinik, Schwerpunkt Hepatologie/Infektiologie CRS
city: Dublin
country: Ireland
facility: St. James' Hosp., Guide Clinic CRS
city: Haifa
country: Israel
facility: Rambam Med. Ctr., Immunology, Allergy & AIDS Institute, B. Rappaport Faculty of Medicine, Technion
city: Rehovot
country: Israel
facility: Kaplan Med. Ctr., Ben Ari Institute of Clinical Immunology CRS
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Med. Ctr., Clinical Immunology Unit and AIDS Ctr. CRS
city: Brescia
country: Italy
facility: Civili di Brescia, 1st Division of Infectious Diseases CRS
city: Brescia
country: Italy
facility: Civili di Brescia, Dept of Infectious & Tropical Disease, Hosp.Spedali Civili of Brescia CRS
city: Firenze
country: Italy
facility: Ospedale S. Maria Annunziata, U.O. Malattie Infettive CRS
city: Milano
country: Italy
facility: Ospedale San Raffaele, Centro San Luigi - Divisione Malattie Infettive CRS
city: Milano
country: Italy
facility: Univ. of Milan, Ospedale Luigi Sacco, Institute of Infectious and Tropical Diseases CRS
city: Modena
country: Italy
facility: Universita degli Studi di Modena e Reggio Emilia, Clinica delle Malattie Infettive e Tropicali CRS
city: Pavia
country: Italy
facility: San Matteo Hospital - University of Pavia, Division of Infectious and Tropical Diseases CRS
city: Roma
country: Italy
facility: Universita La Sapienza, Clinica Universita La Sapienza CRS
city: Osaka
country: Japan
facility: Osaka National Hosp. AIDS Ctr., Clinical Research Institute CRS
city: Tokyo
country: Japan
facility: International Med. Ctr. of Japan CRS
city: Tokyo
country: Japan
facility: Univ. of Tokyo, Research Hosp. of the Institute of Medical Science CRS
city: Casablanca
country: Morocco
facility: Univ. Hosp. Ctr. of the Med. School of Casablanca, Infectious Diseases Unit CRS
city: Amsterdam
country: Netherlands
facility: OLVG -- locatie Prinsengracht, Dept. of Internal Medicine II CRS
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum CRS
city: Amsterdam
country: Netherlands
facility: Stichting Medisch Centrum Jan van Goyen, Dept. of Internal Medicine CRS
city: Groningen
country: Netherlands
facility: Groningen Univ. Hosp., Department of Internal Medicine CRS
city: Haarlem
country: Netherlands
facility: Kennemer Gasthuis, Lokatie EG CRS
city: Tilburg
country: Netherlands
facility: St. Elisabeth Ziekenhuis CRS
city: Oslo
country: Norway
facility: Ulleval Hosp., Dept. of Infectious Diseases CRS
city: Chorzow
country: Poland
facility: Szpital Specjalistyczny, Osrodek Diagnostyki i Terapii AIDS CRS
city: Szczecin
country: Poland
facility: Pomeranian Academy of Medicine (PAM), Dept. of Infectious Diseases and Hepatology CRS
city: Warsaw
country: Poland
facility: Wojewodzki Szpital Zakazny CRS
city: Wroclaw
country: Poland
facility: Wroclaw Univ., School of Med., Dept. of Infectious Diseases, Liver Diseases and AIDS CRS
city: Cascais
country: Portugal
facility: Hospital de Cascais, HDDI, Departamento Medicina Interna CRS
city: Lisboa
country: Portugal
facility: Hosp. de Egas Moniz, Servicio de Infecciologia e Medicina Tropical CRS
city: Lisboa
country: Portugal
facility: Hosp. de Santa Maria, Servico de Doencas Infecciosas CRS
city: Singapore
country: Singapore
facility: Tan Tock Seng Hosp., Infectious Diseases Research Ctr. CRS
city: San Sebastian
country: Spain
facility: Hosp. Donostia CRS
state: Guipuzcoa
city: A Coruna
country: Spain
facility: Hosp. Juan Canalejo, Dept. of Internal Medicine CRS
city: Barcelona
country: Spain
facility: Hosp. Santa Creu i Sant Pau, Servicio de Medicina Interna CRS
city: Barcelona
country: Spain
facility: Hosp. Clinico de Barcelona CRS
city: Barcelona
country: Spain
facility: Hosp. del Mar, Internal Medicine-Infectious Diseases CRS
city: Barcelona
country: Spain
facility: Hosp. Universitari Germans Trias i Pujol, HIV Unit and Retrovirology Lab. CRS
city: Madrid
country: Spain
facility: Hosp. Universitario Gregorio Maranion, Microbiology & Infectious Diseases Unit CRS
city: Madrid
country: Spain
facility: Centro de Investigacion Carlos III, Infectious Diseases Dept. CRS
city: Madrid
country: Spain
facility: Hosp. Severo Ochoa, Internal Medicine and Infectious Diseases CRS
city: Madrid
country: Spain
facility: Hosp. 12 de Octubre, Pabellon de Medicina Communitaria CRS
city: Madrid
country: Spain
facility: Hosp. Clinico San Carlos CRS
city: Madrid
country: Spain
facility: Hosp. la Princesa, Internal Medicine and Infectious Diseases Service CRS
city: Madrid
country: Spain
facility: Hosp. Ramon y Cajal (Madrid) CRS
city: Madrid
country: Spain
facility: Hosp. Universitario La Paz CRS
city: Madrid
country: Spain
facility: Hosp. Universitario Principe de Asturias CRS
city: Murcia
country: Spain
facility: Hosp. Universitario Morales Meseguer CRS
city: Sevilla
country: Spain
facility: Hosp. Virgen del Rocio, Infectious Diseases Service CRS
city: Stockholm
country: Sweden
facility: Karolinska Univ. Hosp. Huddinge, Dept. of Infectious Diseases CRS
city: Stockholm
country: Sweden
facility: Venhalsan, Soder Hosp., Dept. of Infectious Diseases, Karolinska Univ. Hosp. CRS
city: Lugano
country: Switzerland
facility: Regional Hosp. of Lugano (Sede Civico), Ospedale Civico di Lugano, Infectious Diseases Unit CRS
state: Ticino
city: Bangkok
country: Thailand
facility: Siriraj Hosp., Mahidol Univ. INSIGHT CRS
state: Ratchathewi
city: Bangkok
country: Thailand
facility: Chulalongkorn Univ. Hosp., HIV-NAT Research Collaboration CRS
state: Ratchathewi
city: Chiangrai
country: Thailand
facility: Chiang Rai Regional Hosp. INSIGHT CRS
city: Chonburi
country: Thailand
facility: Chonburi Regional Hosp., Dept. of Internal Medicine CRS
city: Khon Kaen
country: Thailand
facility: Khon Kaen Univ., Srinagarind Hosp., Div. of Infectious Diseases & Tropical Medicine, Dept. of Medici
city: Elm Grove
country: United Kingdom
facility: Brighton & Sussex Univ. Hosp. NHS Trust, HIV Research Office CRS
state: Brighton
city: Belfast
country: United Kingdom
facility: Royal Victoria Hosp. Dept. of Genitourinary Medicine CRS
state: Northern Ireland
city: Headington
country: United Kingdom
facility: Churchill Hosp. John Warin Ward CRS
state: Oxford
city: Edinburgh
country: United Kingdom
facility: Western Gen. Hosp., Regional Infectious Diseases Unit CRS
state: Scotland
city: Glasgow
country: United Kingdom
facility: Gartnaval Gen. Hosp., Brownlee Ctr. CRS
state: Scotland
city: Birmingham
country: United Kingdom
facility: Heartlands Hosp. Dept. of Infection & Tropical Disease Outpatients CRS
city: Exeter
country: United Kingdom
facility: Royal Devon & Exeter NHS Foundation Trust, Heavitree Hosp., Dept. of GU Medicine CRS
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary, Dept. of Infection & Tropical Medicine CRS
city: London
country: United Kingdom
facility: Royal London Hosp., Ambrose King Ctr. CRS
city: London
country: United Kingdom
facility: St. Thomas' Hosp., Dept. of GU Medicine CRS
city: London
country: United Kingdom
facility: St. George's Hosp. Clinical Infection UnitCRS
city: London
country: United Kingdom
facility: Chelsea & Westminster Hosp., St. Stephens Ctr. CRS
city: London
country: United Kingdom
facility: King's College Hosp., Caldecot Ctr. Dept. of Sexual Health CRS
city: London
country: United Kingdom
facility: Royal Free Hosp., Dept. of Infection & Immunity, Ian Charleson Day Ctr. CRS
city: London
country: United Kingdom
facility: St. Bartholomew's Hosp., Infection & Immunity Clinical Group CRS
city: London
country: United Kingdom
facility: St. Mary's Hosp. of London, Imperial College School of Medicine CRS
city: London
country: United Kingdom
facility: Univ. College London Med. School, Ctr. for Sexual Health & HIV Research CRS
city: Newcastle Upon Tyne
country: United Kingdom
facility: Newcastle Gen. Hosp., Dept of Infection & Tropical Medicine CRS
city: Peterborough
country: United Kingdom
facility: Edith Cavell Hosp. Dept. of Sexual Health, Clinic E CRS
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hosp., Dept. of GU Medicine Communicable Diseases Unit CRS
Study officials:
affiliation: University of California, San Francisco
name: Donald Abrams, MD
role: STUDY_CHAIR
affiliation: Hospital Jose Maria Ramos Mejia, Buenos Aires, Argentina
name: Marcelo Losso, MD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.