Effect of Intermittent Aldesleukin Treatment With or Without Anti-HIV Drugs in HIV Infected People

NCT00110812 | Completed Phase 2 Results DMC

• 2 other identifiers: ESPRIT 00210053
• Study Type: interventional
• Target: 267
• Locations: 11 countries
• Sites: 36

Brief Summary

The purpose of this study is to determine the effect of short cycles of recombinant interleukin-2 (also known as rIL-2 or aldesleukin) given with or without anti-HIV drugs in HIV infected patients. The effects will be compared with a study group that receives no IL-2 or antiretroviral therapy. Study hypothesis: Intermittent aldesleukin, when given without antiretroviral therapy to patients with early HIV infection, will produce no change in HIV viral load and increases in CD4+ T lymphocyte counts comparable to aldesleukin administered with antiretrovirals.

Conditions

HIV Infections

Keywords

Treatment Naive; IL-2; rIL-2

Outcome Measures

Primary Outcomes (1)

• Mean Change in CD4+ T Lymphocyte Count

  Change in CD4 count from baseline to week 32.

  Week 32

Secondary Outcomes (10)

• Discontinuation of IL-2

  week 32

• Plasma HIV RNA

  At Week 32

• Change in CD4 T Lymphocyte Count

  At Month 12

• HIV-1 Genotype Changes

  after 3rd cycle of IL-2

• Fasting Lipid Profile

  week 32

Study Arms (3)

No IL-2

NO INTERVENTION

Participants will receive no aldesleukin or HAART

IL-2 without ART

EXPERIMENTAL

Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level. Some Group 2 participants may take part in additional cycles of aldesleukin if they meet certain study criteria.

Drug: IL-2

IL-2 with pericycle HAART

EXPERIMENTAL

Participants will receive aldesleukin under the skin twice daily for 5 consecutive days every 8 weeks for 3 cycles, then as needed to maintain CD4 counts at or above a goal level; Group 3 participants will also take HAART for 3 days prior to the start of each aldesleukin cycle, throughout the 5-day aldesleukin cycle, and for 2 days after the end of each aldesleukin cycle (for a maximum of 10 days with each aldesleukin cycle). Some Group 3 participants may take part in additional cycles of aldesleukin if they meet certain study criteria. HAART is not supplied by the study, and choice of drugs is left to the participant and physician. The HAART regimen should include at least one protease inhibitor and at least 2 nucleoside/nucleotide reverse transcriptase inhibitors.

Drug: IL-2

Interventions

IL-2 DRUG

7.5 MIU injected intramuscularly; one arm uses Proleukin together with HAART of choice (protease inhibitor and at least 2 nucleoside/nucleotide reverse transcriptase inhibitors)

Also known as: Proleukin, Aldeskeukin

IL-2 with pericycle HAART; IL-2 without ART

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV infected
• CD4 count of 300 cells/mm3 or more
• Access to a HAART regimen consisting of 1 or more protease inhibitors (PIs) and 2 or more nucleoside or nucleotide reverse transcriptase inhibitors

You may not qualify if:

• Prior use of aldesleukin
• Approved or experimental antiretroviral drug (including hydroxyurea) within 1 year prior to study entry
• Evidence of virologic failure on a PI- or nonnucleoside-based HAART regimen
• Any current indication for continuous HAART, in the opinion of the investigator
• Any contraindication to HAART, in the opinion of the investigator
• Systemic corticosteroids, chemotherapy, or experimental cytotoxic drugs within 45 days of randomization
• Approved or experimental agents with clinically significant immunomodulatory effects within 8 weeks prior to randomization
• History of any AIDS-defining illness or certain other diseases. More information on this criterion can be found in the protocol.
• Concurrent cancer requiring cytotoxic therapy
• Any central nervous system (CNS) abnormality requiring ongoing treatment with antiseizure medication
• Current or prior autoimmune or inflammatory diseases, including inflammatory bowel disease, psoriasis, optic neuritis, or any other autoimmune or inflammatory diseases with potentially life-threatening complications
• Significant heart, lung, kidney, liver, gastrointestinal, CNS, or psychiatric disease OR illicit substance use or abuse that, in the opinion of the investigator, would interfere with the study
• Pregnancy or breastfeeding

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Chiron Corporation: collaborator

Study Sites (36)

VA Greater Los Angeles Healthcare System, Infectious Diseases Section CRS

Los Angeles, California, 90073, United States

Location

Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS

Washington D.C., District of Columbia, 20422, United States

Location

NIH Clinical Ctr., NIAID HIV Clinic CRS

Bethesda, Maryland, 20814-9692, United States

Location

Henry Ford Hosp. CRS

Detroit, Michigan, 48202, United States

Location

Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)

New York, New York, 10037, United States

Location

Lincoln Hosp. & Med. Ctr. CRS

The Bronx, New York, 10451, United States

Location

Providence Portland Med. Ctr., Ambulatory Care and Education Ctr. CRS

Portland, Oregon, 97213, United States

Location

Michael E. DeBakey VAMC CRS

Houston, Texas, 77030, United States

Location

Thomas Street Clinic CRS

Houston, Texas, 77030, United States

Location

South Texas Veterans Health Care System, Immunosuppression Clinic CRS

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth Univ. Medical Ctr. CRS

Richmond, Virginia, 23298, United States

Location

Hosp. Italiano de Buenos Aires, Infectious Diseases Section CRS

Ciudad de Buenos Aires, Buenos Aires, 1199, Argentina

Location

Hosp. Gen. de Agudos JM Ramos Mejia, Servicio de Inmunocomprometidos CRS

Ciudad de Buenos Aires, Buenos Aires, 1221, Argentina

Location

Funcei Crs

Ciudad de Buenos Aires, Buenos Aires, C1425-AWK, Argentina

Location

Caici Crs

Rosario, Provincia de Sante Fe, Argentina

Location

St. Vincent's Hospital CRS

Darlinghurst, New South Wales, 2010, Australia

Location

Queensland Health - AIDS Med. Unit CRS

Brisbane, Queensland, 4000, Australia

Location

Gladstone Road Medical Ctr. CRS

Highgate Hill, Queensland, 4101, Australia

Location

Gold Coast Sexual Health Clinic CRS

Miami, Queensland, 4220, Australia

Location

Carlton Clinic CRS

Carlton, Victoria, 3053, Australia

Location

Fundacion Arriaran CRS

Santiago, Chile

Location

Ospedale San Raffaele S.r.l. CRS

Milan, 20127, Italy

Location

Univ. of Milan, Ospedale Luigi Sacco, Institute of Infectious and Tropical Diseases CRS

Milan, 20157, Italy

Location

Univ. Hosp. Ctr. of the Med. School of Casablanca, Infectious Diseases Unit CRS

Casablanca, Morocco

Location

Wojewodzki Szpital Zakazny CRS

Warsaw, Poland

Location

Hospital de Cascais, HDDI, Departamento Medicina Interna CRS

Cascais, Portugal

Location

Hosp. de Egas Moniz, Servicio de Infecciologia e Medicina Tropical CRS

Lisbon, Portugal

Location

Hosp. de Santa Maria, Servico de Doencas Infecciosas CRS

Lisbon, Portugal

Location

Hosp. Clinico de Barcelona CRS

Barcelona, Spain

Location

Chulalongkorn University Hospital CRS

Bangkok, Ratchathewi, Thailand

Location

Chiang Rai Regional Hosp. INSIGHT CRS

Chiangrai, Thailand

Location

Khon Kaen Univ., Srinagarind Hosp., Div. of Infectious Diseases & Tropical Medicine, Dept. of Medici

Khon Kaen, Thailand

Location

Brighton & Sussex Univ. Hosp. NHS Trust, HIV Research Office CRS

Elm Grove, Brighton, United Kingdom

Location

Leicester Royal Infirmary, Dept. of Infection & Tropical Medicine CRS

Leicester, United Kingdom

Location

St. Bartholomew's Hosp., Infection & Immunity Clinical Group CRS

London, EC1A 7BE, United Kingdom

Location

St. Mary's Hosp. of London, Imperial College School of Medicine CRS

London, W2 1NY, United Kingdom

Location

Related Publications (6)

• Anaya JP, Sias JJ. The use of interleukin-2 in human immunodeficiency virus infection. Pharmacotherapy. 2005 Jan;25(1):86-95. doi: 10.1592/phco.25.1.86.55629.

  PMID: 15767224 BACKGROUND

• de Boer AW, Markowitz N, Lane HC, Saravolatz LD, Koletar SL, Donabedian H, Yoshizawa C, Duliege AM, Fyfe G, Mitsuyasu RT. A randomized controlled trial evaluating the efficacy and safety of intermittent 3-, 4-, and 5-day cycles of intravenous recombinant human interleukin-2 combined with antiretroviral therapy (ART) versus ART alone in HIV-seropositive patients with 100-300 CD4+ T cells. Clin Immunol. 2003 Mar;106(3):188-96. doi: 10.1016/s1521-6616(02)00038-4.

  PMID: 12706405 BACKGROUND

• Davey RT Jr, Murphy RL, Graziano FM, Boswell SL, Pavia AT, Cancio M, Nadler JP, Chaitt DG, Dewar RL, Sahner DK, Duliege AM, Capra WB, Leong WP, Giedlin MA, Lane HC, Kahn JO. Immunologic and virologic effects of subcutaneous interleukin 2 in combination with antiretroviral therapy: A randomized controlled trial. JAMA. 2000 Jul 12;284(2):183-9. doi: 10.1001/jama.284.2.183.

  PMID: 10889591 BACKGROUND

• Marchetti G, Franzetti F, Gori A. Partial immune reconstitution following highly active antiretroviral therapy: can adjuvant interleukin-2 fill the gap? J Antimicrob Chemother. 2005 Apr;55(4):401-9. doi: 10.1093/jac/dkh557. Epub 2005 Feb 24.

  PMID: 15731201 BACKGROUND

• Pett SL, Kelleher AD. Cytokine therapies in HIV-1 infection: present and future. Expert Rev Anti Infect Ther. 2003 Jun;1(1):83-96. doi: 10.1586/14787210.1.1.83.

  PMID: 15482104 BACKGROUND

• Tavel JA; INSIGHT STALWART Study Group; Babiker A, Fox L, Gey D, Lopardo G, Markowitz N, Paton N, Wentworth D, Wyman N. Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: the STALWART study. PLoS One. 2010 Feb 23;5(2):e9334. doi: 10.1371/journal.pone.0009334.

  PMID: 20186278 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Interleukin-2; aldesleukin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Limitations and Caveats

All randomized patients were followed through 28 Feb 2009. A subset of 222 consenting patients were followed 2 additional years, through 28 Feb 2011.

Results Point of Contact

• Title: Deborah Wentworth
• Organization: University of Minnesota

wentw001@umn.edu

612-726-9005

Study Officials

• Jorge Tavel, MD

  National Institute for Allergy and Infectious Diseases, National Institutes of Health

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2005
• First Posted: May 16, 2005
• Study Start: September 1, 2005
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: November 4, 2021
• Results First Posted: May 12, 2014

Record last verified: 2014-04

Locations

TH (3); GB (4); AU (5); MO (1); AR (4); PL (1); PT (3); US (11); CL (1); ES (1); IT (2)