Phase II/III Study Evaluating the Effect of IL-2 on Preservation of the CD4 T-Lymphocytes After Interruption of Antiretroviral Treatment in HIV-Infected Patients With CD4 T-Lymphocyte Count Greater Than 500 Cells/mm3 Who Received Antiretroviral Tx

NCT00071890 | Completed Phase 2 Results DMC

• 3 other identifiers: 04001804-I-0018ANRS 118 ILIADE
• Study Type: interventional
• Target: 148
• Locations: 2 countries
• Sites: 2

Brief Summary

This study will examine whether interleukin-2 (IL-2) given before the interruption of antiretroviral (ARV) treatment could significantly extend the period of time that a patient is temporarily not taking ARV treatment and also preserve CD4 counts above 350 cells per microliter. There will be an evaluation of the toxicity, or extremely harmful effects, of ARV, and the effect on quality of life. The use of ARV medications has greatly improved the condition and mortality of HIV-infected patients. But when used long term, those medications have been associated with great toxicities and medication fatigue. As a result, patients may not adhere to ARV use, and resistance to viruses may grow. The CD4 molecule is on the surface of helper T-lymphocytes, or T-helper cells. It serves as the primary receptor for HIV-1 and HIV-2, allowing the virus to gain entry into its host. The CD4 count increases immediately in response to ARV, giving an estimate of the state of a patient's immune system. Thus, it is a strong marker of the immediate risk of an opportunistic infection, one that takes advantage of a person's weakened immune system. IL-2 is a molecule naturally produced by activated T cells. In patients with HIV, IL-2 treatment can increase CD4 counts but the clinical importance of this increase is not clear. This study will compare the decline in CD4 count, when ARV is interrupted, in two random groups of participants: (1) those who will receive three cycles of IL-2 (one every 8 weeks) in combination with ARV therapy for the first 24 weeks of the study before stopping ARV and (2) those who will receive ARV therapy without IL-2 for 24 weeks before stopping ARV. Patients 18 years of age or older who have HIV-1 infection and who have been on ARV therapy for at least 1 year, and who currently have a CD4 count 500 cells per microliter or higher and never had a CD4 count of less than 200 cells per microliter and a viral load less than the limit of detection, may be eligible for this study. Participants will undergo the following procedures and tests:

• Physical examination.
• Blood tests to measure blood lipids (fats), sugar, complete blood count including platelets, and chemistries.
• Assessment of fat distribution.
• Questionnaire about quality of life. In addition, those participants who are randomly placed in the group receiving IL-2 and ARV will get an echocardiogram at the beginning of the study and at week 24. They will receive a starting dose of 6 million units of IL-2 as an injection under the skin twice a day. Each of the three IL-2 cycles will last 5 days. After the 24-week period, participants in both groups will stop taking ARV medications if their CD4 count is still equal to or greater than 500 cells per microliter. The study will continue into 120 weeks. Participants will be asked to continue to visit the clinic every 8 weeks for evaluation of their viral load and CD4 counts. Every 24 weeks, they will be asked to answer a questionnaire about their quality of life. Blood tests and other measurements will also be done as follow-up.

Conditions

HIV Infections

Keywords

Interleukin 2; Treatment Interruption; HIV

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Without Failure of Strategy From Week 0 to Week 72

  A failure of strategy is defined on the first occurrence of one of the following events: * CD4 T-lymphocyte count becomes \< 350 cells/mm3 between Wk0 and Wk72 (count confirmed by a 2nd measurement after 2-4 weeks * Planned interruption of therapy at Wk24 cannot be done for any reason; * Anti-retroviral treatment is restarted between Wk24 and Wk72 for any reason * Subject experiences clinical progression of HIV infection to a stage C AIDS diagnosis (appendix I) * Subject expires between Wk0 and Wk72 (whatever the cause of death) * Subject is lost to follow up

  week 72

Secondary Outcomes (2)

• Changes in CD4 Counts at Week 72

  week 72

• AIDS Events

  Overall study

Study Arms (2)

Interleukin 2 group

ACTIVE COMPARATOR

HAART (standard of care) and three cycles of IL-2

Drug: Interleukin 2; Drug: HAART; Drug: Treatment interruption

Control group

ACTIVE COMPARATOR

HAART alone

Drug: HAART; Drug: Treatment interruption

Interventions

Interleukin 2 DRUG

Three cycles of IL-2 (6 MUI bid during 5 days = one cycle)

Also known as: Interleukin-2, IL-2, aldesleukin

Interleukin 2 group

HAART DRUG

HAART from week 0 to week 24

Also known as: Antiretroviral treatment

Control group; Interleukin 2 group

Treatment interruption DRUG

HAART is interrupted from week 24 in both arms

Control group; Interleukin 2 group

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 18 years.
• HIV-1 infection confirmed by ELISA and Western Blot before screening.
• Category A or B HIV-1 infection.
• Antiretroviral treatment:
• started at least 12 months prior to screening visit;
• stable and continuous for at least 12 weeks prior to screening visit;
• modified no more than once for virologic failure.
• IL-2 naive
• CD-4(+) T-lymphocyte count greater than or equal to 500 cells/mm(3) in the twelve weeks prior to screening (historical) and at screening.
• Nadir CD4(+) T-lymphocyte count greater than or equal to 200 cells/mm(3) prior to screening visit (that is, no measurement whose values may be less than 200/mm(3) since diagnosis of the HIV infection.
• Plasma HIV RNA less than 50 copies/ml in the 12 weeks preceding screening (historical, less than limit of detection if different method and/or cut off used) and at screening.
• For women of child-bearing age: use of effective contraception (hormonal such as birth control pill or injections, intrauterine device, surgical sterilization and/or mechanical barrier methods such as diaphragm or condoms); for all participants agreement to fully comply with prevention of transmission recommendations during periods of viremia if sexually active (latex condoms with or without additional barrier methods).
• Desire to interrupt antiretroviral therapy.
• Ability to sign informed consent (no later than W-2).

You may not qualify if:

• Previous treatment with IL-2.
• Combined treatment with interferon, other interleukins, anti-HIV vaccines, systemic (not topical or inhaled) corticosteroids and hydroxyurea within the previous 12 weeks.
• Diagnosis of AIDS.
• Pregnant, lactating woman desiring conception or not using contraception.
• Hemoglobin less than 10 g/dl; neutrophils less than 1,000/mm(3); platelets less than 50,000/mm(3); creatinine greater than 1.5 times the upper limit of normal (N); bilirubin greater than 3N; AST or ALT greater than 3 N.
• Progressive disease of malignant, psychiatric, cardiac, pulmonary, thyroid, renal or neurological (peripheral or central) origin or severe disorders of hemostasis.
• Severe uncontrolled hypertension.
• Previous or progressive pathology contraindicating the administration of IL-2.
• History of extensive psoriasis, Crohn's disease or auto-immune disease involving severe complications.
• HTLV-1 infection (ELISA positive).
• Hepatitis B virus co-infection treated with lamivudine or tenofovir or adefovir.
• Since atazanavir use can be associated with higher bilirubin levels (mostly indirect) in the absence of clinical consequences, subjects on atazanavir with bilirubin up to 4.5 times N may be allowed to participate if the levels have been stable and after approval by the PI or the PI designated covering physician.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• ANRS, Emerging Infectious Diseases: collaborator

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Hospital Henri Mondor

Créteil, France

Location

Related Publications (4)

• Arno A, Ruiz L, Juan M, Jou A, Balague M, Zayat MK, Marfil S, Martinez-Picado J, Martinez MA, Romeu J, Pujol-Borrell R, Lane C, Clotet B. Efficacy of low-dose subcutaneous interleukin-2 to treat advanced human immunodeficiency virus type 1 in persons with </=250/microL CD4 T cells and undetectable plasma virus load. J Infect Dis. 1999 Jul;180(1):56-60. doi: 10.1086/314831.

  PMID: 10353861 BACKGROUND

• Carr A, Emery S, Lloyd A, Hoy J, Garsia R, French M, Stewart G, Fyfe G, Cooper DA. Outpatient continuous intravenous interleukin-2 or subcutaneous, polyethylene glycol-modified interleukin-2 in human immunodeficiency virus-infected patients: a randomized, controlled, multicenter study. Australian IL-2 Study Group. J Infect Dis. 1998 Oct;178(4):992-9. doi: 10.1086/515653.

  PMID: 9806026 BACKGROUND

• Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet. 2000 Oct 21;356(9239):1423-30. doi: 10.1016/S0140-6736(00)02854-3.

  PMID: 11052597 BACKGROUND

• Alexandre M, Prague M, Lhomme E, Lelievre JD, Wittkop L, Richert L, Levy Y, Thiebaut R. Definition of Virological Endpoints Improving the Design of HIV Cure Strategies Using Analytical Antiretroviral Treatment Interruption. Clin Infect Dis. 2024 Dec 17;79(6):1447-1457. doi: 10.1093/cid/ciae235.

  PMID: 38819800 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Interleukin-2; aldesleukin; Antiretroviral Therapy, Highly Active; Treatment Interruption

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; Drug Therapy, Combination; Drug Therapy; Therapeutics; Treatment Adherence and Compliance; Attitude to Health; Delivery of Health Care; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Pr G. Chene
• Organization: INSERM U897 Bordeaux FRANCE

genevieve.chene@isped.u-bordeaux2.fr

557571392

Study Officials

• Yves Lévy, PHD

  CHU Henri Mondor Créteil, FRANCE

  STUDY CHAIR

• Irini Sereti, MD

  National Institute of Allergy and Infectious Diseases (NIAID)

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: November 3, 2003
• First Posted: November 4, 2003
• Study Start: October 1, 2003
• Primary Completion: December 1, 2007
• Study Completion: December 1, 2007
• Last Updated: October 5, 2010
• Results First Posted: October 5, 2010

Record last verified: 2010-09

Locations

US (1); FR (1)