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

Condition(s) targeted: HIV Infections

Intervention: Aldesleukin (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Jorge Tavel, MD, Study Chair, Affiliation: National Institute for Allergy and Infectious Diseases, National Institutes of Health

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.

Official title: A Randomized, Open-Label, International Study of Subcutaneous Recombinant Interleukin-2 (rIL-2, Aldesleukin) With and Without Concomitant Antiretroviral Therapy in Patients With HIV-1 Infection and CD4+ Cell Counts of 300 Cells/mm3 or More: Study of Aldesleukin With and Without Concomitant Antiretroviral Therapy

Study design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Mean change in CD4+ T lymphocyte count

Secondary outcome:

Grade 3 and 4 events

Therapy modification as defined by the protocol

Plasma HIV RNA

CD4 T lymphocyte count

HIV-1 genotype changes

Fasting lipid profile and thyroid stimulating hormone and hepatic transaminase levels

Detailed description: Highly active antiretroviral therapy (HAART) has dramatically improved prognosis and lowered morbidity and mortality rates for HIV infected patients. However, significant drug toxicities, difficulties with patient compliance to HAART regimens, and development of drug resistance highlight the need for less toxic, immune-based strategies. Aldesleukin is a synthetic protein that can increase CD4 counts; it is currently approved by the Food and Drug Administration (FDA) for use in patients with metastatic melanoma and renal cell carcinoma. Previous studies of aldesleukin in HIV infected patients indicated that increased CD4 counts can persist for years after aldesleukin administration, and aldesleukin given with HAART may also lead to significant lowering of viral load. This study will examine the immunologic effects of intermittent cycles of aldesleukin administered with and without HAART as compared to no therapy in HIV infected patients.

This study will last approximately 18 months. Participants will be randomly assigned to one of three groups at study entry. Group A will receive no aldesleukin or HAART. Group B 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 C 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 C 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). HAART will not be provided by the study. Some Group B and C participants may take part in additional cycles of aldesleukin if they meet certain study criteria.

All participants in this study will have at least 8 study visits; these visits will occur at study entry and Weeks 4, 8, 12, 16, 20, 24, and 32. Additional follow-up visits will occur every 4 months to the end of the study. Blood collection will occur at all visits and will include tests for CD4 count and viral load. Groups B and C will have additional blood collection within 4 days prior to the start of each aldesleukin cycle. On the last day of each aldesleukin cycle, Groups B and C will be assessed for toxicities, adverse events, and adherence to the aldesleukin daily injections; they will also have another blood collection. Group C participants will have an additional blood collection for HIV genotyping after they have completed their third aldesleukin cycle.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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

Klinik I fur Innere Medizin der Universitat zu Koln, Cologne 50937, Germany; Active, not recruiting

University of Wuerzburg, Wuerzburg 97080, Germany; Active, not recruiting

Medizinische Hochschule Hannover, Hannover, Germany; Recruiting
Kirsten Hoeper, RN, Phone: 49-0-511-532-5395, Email: Hoeper.kirsten@mhhannover.de
Matthias Stoll, Principal Investigator

Royal Victoria Hospital, Belfast, Ireland; Recruiting
Sinead McKeman, Phone: 028-90-634548, Email: sinead.mckernan@royalhospitals.n-i.nhs.uk
Raymond D Maw, MD, Principal Investigator

Ospedale S.M. Annunziata, Antella-Firenze 50011, Italy; Recruiting
Massimo Di Pietro, MD, Phone: 39 055 249 6233, Email: massimo.dipietro@asf.toscana.it
Francesco Mazzetto, MD, Principal Investigator

Institute of Infectious & Tropical Diseases, Univ. of Milan, Milano 20157, Italy; Recruiting
Roberto Rossotti, MD, Phone: (390) 239-042668, Email: ctuhiv@unimi.it
Mauro Moroni, MD, Principal Investigator

Wroclaw University School of Medicine, Wroclaw, Poland; Active, not recruiting

Wojewodzki Szpital Zakazny, Warszawa, Poland; Recruiting
Elzbieta Bakowska, MD, Phone: 48-22-632-22-86, Email: bakowska@cdit-aids.med.pl
Andrzej Horban, PhD, Principal Investigator

Hospital de Santa Maria, Lisbon, Portugal; Recruiting
Fancisco Antunes, Phone: 351-21-780-52-64, Email: ip231874@mail.ip.pt
Francisco Antunes, Principal Investigator

Hospital de Cascais, Cascais, Portugal; Recruiting
Jose A. Viegas de Conceica Vera, Phone: 351-967-36218, Email: hddi@chcascais.min-saude.pt
Jose A. Viegas de Conceica Vera, Principal Investigator

Gartnaval General Hospital, Glasgow G12 0YN, Seychelles; Recruiting
Lorna McLean, RN, Phone: 0141-211-0297, Email: lorna.mclean@northglasgow.scot.nhs.uk
Ray Fox, MD, Principal Investigator

Hospital Universitario Gregorio Maranon, Madrid, Spain; Recruiting
Paloma Gijon, MD, Phone: 34-91-586-67-40, Email: msnachezf.HGUGM@salud.madrid.org
Emilio Bouza, MD, Principal Investigator

Hospital Universitario Germans Trias i Pujo, Barcelona, Spain; Recruiting
Antoni J. Pastor, MD, Phone: 00-34-93-465-78-97, Email: ajou@ns.hugtip.scs.es
Boneventura C. Sala, MD, Principal Investigator

Hospital Virgen del Rocio, Sevilla, Spain; Recruiting
Rosario M. Alcazar, MD, Phone: 34-955-01-20-10, Email: rodeca@eresmas.net
Luiz Fernando L. Cortes, MD, PhD, Principal Investigator

Hospital Santa Ceru i Sant Pau, Barcelona, Spain; Recruiting
Montserrat Fuster, MD, Phone: 34-93-291-93-43, Email: mfuster@hsp.santpau.es
Pere D. Pedrol, MD, PhD, Principal Investigator

Hospital Clinico de Barcelona, Barcelona, Spain; Recruiting
Maria Martinez Rebollar, MD, Phone: +34 93 227 54 00, Ext: 2941, Email: rebollar@clinic.ub.es
Jose Maria Gatell, MD, Principal Investigator

Hospital do la Princesa, Madrid, Spain; Recruiting
Ignacio Santos Gil, MD, Phone: +34 91 520 22 36, Email: isantosg@hotmail.com
Jesus Sanz, MD, Principal Investigator

Khon Kaen University, Khon Kaen, Thailand; Not yet recruiting
Ampai Poungkajohn, BN, Phone: 664-336-3169, Email: apoungkajohn@yahoo.com
Ploenchan Chetchotisakd, MD, Principal Investigator

St. Bartholomews Hospital, London EC1A 7BE, United Kingdom; Recruiting
James Hand, Phone: 020-7601-7508, Email: james.hand@bartsandthelondon.nhs.uk

St. Mary's Hospital, London W2 1NY, United Kingdom; Recruiting
Scott Mullaney, Phone: 020-7886-6499, Email: s.mullaney@imperial.ac.uk

Chelsea & Westminster Hospital, London SW10 9NH, United Kingdom; Active, not recruiting

Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom; Recruiting
Jessica Osorio, Phone: 020-8846-6505, Email: jessica.osorio@bartsandthelondon.nhs.uk

St. Bartholomew's Hospital, London EC1A 7BE, United Kingdom; Recruiting
James Hand, Phone: 020-7601-7508, Email: james.hand@bartsandthelondon.nhs.uk

University Hospital Centre of the Medical School of Casablan, Morocco, United Kingdom; Recruiting
Kamal Marhoum El Filali, PhD, Phone: 212-22-22-78-31, Email: himmick@casanet.net.ma
Hakima Himmich, MD, Principal Investigator

John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom; Recruiting
Brian J. Angus, MD, Phone: 01865-22-0289, Email: brian.angus@ndm.ox.ac.uk
Brian J. Angus, MD, Principal Investigator

Birmingham Heartlands Hospital, Birmingham B9 5SS GB, United Kingdom; Recruiting
Gerry Gilleran, Phone: 0121 424 0644, Email: gerry.gilleran@heartofengland.nhs.uk
David J. White, MD, Principal Investigator

Royal Sussex County Hospital, Brighton, BN2 1ES, United Kingdom; Recruiting
Nicky Perry, Phone: 01-27-352-3079, Email: nicky.perry@bsuh.nhs.uk

Chulalongkorn Hospital, Pathumwan, Bangkok 10330, Thailand; Recruiting
Chris Duncombe, Phone: 66-2-255-7334, Email: chris.d@hivnat.org

Hospital General de Agudos Jose Maria Ramos Mejia, Pabellon de Cli, Buenos Aires 1221, Argentina; Recruiting
Leonardo D Lourtau, MD, Phone: 5411-4931-5252, Email: llourtau@hivramos.org.ar

Hospital Italiano de Bueno Aires, Potosi 4215, Buenos Aires 1199, Argentina; Recruiting
Marisa del Lujan Sanchez, MD, Phone: 5411-4959-0393, Email: Marisa.sanchez@hospitalitaliano.org.ar

FUNCEI, French 3085, Buenos Aires C1425-AWK, Argentina; Recruiting
Diego Fridman, MD, Phone: 54-11-5236-7772, Email: inv@cei.com.ar

VA Greater Los Angeles Healthcare System, Los Angeles, California 90073, United States; Recruiting
Debbie Wilson, Phone: 310-478-3711, Ext: 42745, Email: Debbie.Wilson2@med.va.gov

Washington DC VA Medical Center, Washington, District of Columbia 20422, United States; Recruiting
Douglas Thomas, Phone: 202-745-8301, Ext: 7930, Email: douglas.thomas4@med.va.gov

Hospital de Egas Moniz Portugal, Tropical Rua da Ju, Lisban 1349-019 PT, Portugal; Recruiting
Maria Isabel V. Aldir, MD, Phone: 351-21-365-0030
Kamal Mansinho, MD, Principal Investigator

NIH Clinical Center, Bethesda, Maryland 20814-9692, United States; Recruiting
Barbara Hahn, Phone: 301-435-8007, Email: bhahn@niaid.nih.gov

Henry Ford Hospital, Detroit, Michigan 48202, United States; Recruiting
Linda Makohon, RN, BSN, Phone: 313-916-2570, Email: lmakoho1@hfhs.org

Ospedale San Raffaele, Malattie I, Milano 20127, Italy; Not yet recruiting
Silvia Nozza, MD, Phone: +39 02 26437930, Email: silvia.nozza@hsr.it

St.Vincent's Hospital, Darlinghurst, New South Wales 2010, Australia; Recruiting
Richard Norris, Phone: 61-2-8382-2576, Email: rnorris@stvincents.com.au

Holdsworth House General Practice, Darlinghurst, New South Wales 2010, Australia; Active, not recruiting

Harlem Hospital Center, New York, New York 10037, United States; Recruiting
Luis Fuentes, Phone: 212-939-2957, Email: laf2@columbia.edu

Oregon Health Sciences University, Porland, Oregon 97201, United States; Recruiting
Norma Martinez, RN, MEd, CNM, Phone: 503-229-8428, Email: norma@reg.org

Providence Portland Medical Center, Portland, Oregon 97213, United States; Recruiting
Norma Martinez, RN, Phone: 503-229-8428, Email: norma@reg.org

CAICI, Rosario, Provincia de Sante Fe, Argentina; Recruiting
Carla Somenzini, MD, Phone: 54-341-424-8045, Email: somenzinic@arnet.com.ar

Gold Coast Sexual Clinic, Miami, Queensland 4220, Australia; Recruiting
Tammy Schmidt, Phone: 61-7-5576-9033, Email: tammy_schmidt@health.qld.gov.au

AIDS Medical Unit, Brisbane, Queensland 4000, Australia; Recruiting
Paul Negus, RN, Phone: 61-7-3837-5622, Email: paul_negus@health.qld.gov.au

Gladstone Road Medical Centre, Highgate Hill, Queensland 4101, Australia; Recruiting
David Youds, RN, Phone: 61-7-3844-9599, Email: d.youds@grmc.com.au

South Texas Veteran's Health Care System, San Antonio, Texas 78229, United States; Recruiting
Nancy Toro, MD, Phone: 210-949-3076, Email: Nancya.toro@med.va.gov

Thomas Street Clinic, Houston, Texas 77030, United States; Recruiting
Hilda Cuervo, Phone: 713-500-6751, Email: hilda.cuervo@uth.tmc.edu

Veteran's Affairs Medical Center - Houston, Houston, Texas 77030, United States; Recruiting
Eusebia Calvillo, RN, Phone: 713-794-8797, Email: Eusebia.Calvillo-Stevens@med.va.gov

University Clinical Research Center, Houston, Texas 77030, United States; Recruiting
Hilda Cuervo, Phone: 713-500-6751, Email: hilda.cuervo@uth.tmc.edu

Michael E. DeBakey VA Medical Center, Houston, Texas 77030, United States; Recruiting
Eusebia Calvillo, Phone: 713-794-8797, Email: Eusebia.Calvillo-Stevens@med.va.gov

VCU Health Systems, Richmond, VA 23298, United Kingdom; Recruiting
Vicky Watson, Phone: 804-828-3450, Email: vmwatson@mail.vcu.edu

Carlton Clinic, Carlton, Victoria 3053, Australia; Recruiting
Kaye Lowe, Phone: 61-3-9347-9422, Email: kaye.lowe@maynemc.com

The Centre Clinic, St. Kilda, Victoria 3182, Australia; Recruiting
Helen Wood, RN, Phone: 61-3-9525-5866, Email: hpwood@optusnet.com.au

MCV ID Clinic, Richmond, Virginia 23298, United States; Recruiting
Vicky W. Watson, RN, Phone: 804-828-3450, Email: vmwatson@mail1.vcu.edu

Royal Perth Hospital, Perth, Western Australia 6847, Australia; Recruiting
Jenny Skett, Phone: 61-8-9224-3429, Email: jenny.skett@health.wa.gov.au

Click here for more information on aldesleukin

Haga clic aquí para ver información sobre este ensayo clínico en español.

Related publications:

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

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.

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.

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. Epub 2005 Feb 24.

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

Starting date: November 2005
Ending date: October 2010
Last updated: September 25, 2008