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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00004978




Registration number
NCT00004978
Ethics application status
Date submitted
10/03/2000
Date registered
31/08/2001
Date last updated
6/05/2013

Titles & IDs
Public title
An International Study to Evaluate Recombinant Interleukin-2 in HIV Positive Patients Taking Anti-retroviral Therapy
Scientific 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
Secondary ID [1] 0 0
5U01AI046957
Secondary ID [2] 0 0
ESPRIT 001
Universal Trial Number (UTN)
Trial acronym
ESPRIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Recombinant interleukin-2 (rIL-2)

Experimental: rIL-2 - Recombinant interleukin-2 (rIL-2) therapy used with combination anti-HIV medication of choice.

No Intervention: No rIL-2 - Control arm uses anti-HIV medication of choice without rIL-2.


Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
from randomization through study end - median of 7.6 years follow-up
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
from randomization through study end - median of 7.6 years follow-up
Secondary outcome [2] 0 0
Number of Participants Who Died From Any Cause
Timepoint [2] 0 0
from randomization through study end - median of 7.6 years follow-up
Secondary outcome [3] 0 0
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
Timepoint [3] 0 0
from randomization through 15 November 2008 - median of 7.6 years follow-up
Secondary outcome [4] 0 0
Absolute CD4 Cell Counts Averaged Throughout Followup - Average of all available CD4+ cell counts measured at follow-up visits
Timepoint [4] 0 0
from randomization through study end - median of 7.6 years follow-up
Secondary outcome [5] 0 0
Plasma HIV RNA Levels - log10 HIV-RNA averaged throughout follow-up
Timepoint [5] 0 0
From randomization through study end - median of 7.6 years follow-up
Secondary outcome [6] 0 0
Number of Participants With Changes in Anti-retroviral Treatment (ART) - Number of participants who changed ART at least once during the study period.
Timepoint [6] 0 0
From randomization through study end - median of 7.6 years follow-up
Secondary outcome [7] 0 0
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.
Timepoint [7] 0 0
From randomization through study end - median of 7.6 years follow-up
Secondary outcome [8] 0 0
Pattern of Use of Prophylaxis for Opportunistic Infections - Number of participants using pneumocystis pneumonia (PCP) prophylaxis at the last attended followup visit.
Timepoint [8] 0 0
last followup visit - median of 7.6 years follow-up
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
From randomization through study end - median of 7.6 years follow-up

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Interchange General Practice CRS - Canberra
Recruitment hospital [2] 0 0
Canberra Hosp., Canberra Sexual Health Clinic CRS - Woden
Recruitment hospital [3] 0 0
Burwood Road Gen. Practice CRS - Burwood
Recruitment hospital [4] 0 0
St. Vincent's Hospital CRS - Darlinghurst
Recruitment hospital [5] 0 0
Taylor Square Private Clinic CRS - Darlinghurst
Recruitment hospital [6] 0 0
Holdsworth House Gen. Practice CRS - Darlinghurst
Recruitment hospital [7] 0 0
John Hunter Hosp., Immunology & Infectious Diseases Unit CRS - Newcastle
Recruitment hospital [8] 0 0
407 Doctors CRS - Surry Hills
Recruitment hospital [9] 0 0
Albion Street Ctr. CRS - Surry Hills
Recruitment hospital [10] 0 0
Queensland Health - AIDS Med. Unit CRS - Brisbane
Recruitment hospital [11] 0 0
Cairns Base Hosp., Sexual Health Services CRS - Cairns
Recruitment hospital [12] 0 0
Gladstone Road Medical Ctr. CRS - Highgate Hill
Recruitment hospital [13] 0 0
Nambour Gen. Hosp. CRS - Nambour
Recruitment hospital [14] 0 0
Royal Adelaide Hosp. CRS - Adelaide
Recruitment hospital [15] 0 0
The Care & Prevention Programme CRS - Adelaide
Recruitment hospital [16] 0 0
Carlton Clinic CRS - Carlton
Recruitment hospital [17] 0 0
The Alfred Hosp., Clinical Research - Infectious Diseases Unit CRS - Melbourne
Recruitment hospital [18] 0 0
Prahran Market Clinic CRS - Melbourne
Recruitment hospital [19] 0 0
Northcote Clinic CRS - Northcote
Recruitment hospital [20] 0 0
Royal Melbourne Hosp., Victorian Infectious Diseases Service CRS - Parkville
Recruitment hospital [21] 0 0
The Ctr. Clinic INSIGHT CRS - St. Kilda
Recruitment hospital [22] 0 0
Royal Perth Hospital CRS - Perth
Recruitment hospital [23] 0 0
Gold Coast Sexual Health Clinic CRS - Miami, Queensland
Recruitment postcode(s) [1] 0 0
2601 - Canberra
Recruitment postcode(s) [2] 0 0
2606 - Woden
Recruitment postcode(s) [3] 0 0
2134 - Burwood
Recruitment postcode(s) [4] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [5] 0 0
- Darlinghurst
Recruitment postcode(s) [6] 0 0
2305 - Newcastle
Recruitment postcode(s) [7] 0 0
2010 - Surry Hills
Recruitment postcode(s) [8] 0 0
- Surry Hills
Recruitment postcode(s) [9] 0 0
- Brisbane
Recruitment postcode(s) [10] 0 0
4870 - Cairns
Recruitment postcode(s) [11] 0 0
4101 - Highgate Hill
Recruitment postcode(s) [12] 0 0
4560 - Nambour
Recruitment postcode(s) [13] 0 0
5000 - Adelaide
Recruitment postcode(s) [14] 0 0
- Carlton
Recruitment postcode(s) [15] 0 0
3004 - Melbourne
Recruitment postcode(s) [16] 0 0
- Melbourne
Recruitment postcode(s) [17] 0 0
3070 - Northcote
Recruitment postcode(s) [18] 0 0
3052 - Parkville
Recruitment postcode(s) [19] 0 0
- St. Kilda
Recruitment postcode(s) [20] 0 0
- Perth
Recruitment postcode(s) [21] 0 0
- Miami, Queensland
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
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United States of America
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Colorado
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United States of America
State/province [3] 0 0
District of Columbia
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United States of America
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Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
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Illinois
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United States of America
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Louisiana
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Maryland
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Michigan
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Minnesota
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New Jersey
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New York
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Oregon
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Pennsylvania
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United States of America
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Texas
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United States of America
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Virginia
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Argentina
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Buenos Aires
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Argentina
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Provincia de Santa Fe
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Argentina
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Cordoba
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Argentina
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La Plata
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Argentina
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Mendoza
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Austria
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Vienna
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Austria
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Wien
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Belgium
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Bruxelles
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Brazil
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Sao Paulo
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British Columbia
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Nova Scotia
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Ontario
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Quebec
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Saskatchewan
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Aalborg
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Copenhagen
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Hamburg
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Heidelberg
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Koln
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Munchen
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Wuerzburg
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Ireland
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Dublin
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Israel
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Haifa
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Israel
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Rehovot
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Israel
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Tel Aviv
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Italy
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Brescia
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Italy
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Firenze
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Italy
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Milano
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Italy
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Modena
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Italy
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Pavia
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Italy
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Roma
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Japan
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Osaka
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Japan
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Tokyo
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Morocco
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Amsterdam
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Groningen
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Haarlem
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Netherlands
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Tilburg
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Oslo
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Poland
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Chorzow
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Szczecin
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Warsaw
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Wroclaw
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Portugal
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Cascais
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Portugal
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Lisboa
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Singapore
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Singapore
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Spain
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Guipuzcoa
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Spain
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A Coruna
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Spain
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Barcelona
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Spain
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Madrid
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Spain
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Murcia
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Spain
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Sevilla
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Sweden
State/province [93] 0 0
Stockholm
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Switzerland
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Ticino
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Thailand
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Ratchathewi
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Thailand
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Chiangrai
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Thailand
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Chonburi
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Thailand
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Khon Kaen
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United Kingdom
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Brighton
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United Kingdom
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Northern Ireland
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United Kingdom
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Oxford
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United Kingdom
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Scotland
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United Kingdom
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Birmingham
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United Kingdom
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Exeter
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United Kingdom
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Leicester
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United Kingdom
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London
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United Kingdom
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Newcastle Upon Tyne
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United Kingdom
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Peterborough
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United Kingdom
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Sheffield

Funding & Sponsors
Primary sponsor type
Government body
Name
National Institute of Allergy and Infectious Diseases (NIAID)
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Chiron Corporation
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00004978
Trial related presentations / publications
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Donald Abrams, MD
Address 0 0
University of California, San Francisco
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications