NIH Clinical Research Studies

Protocol Number: 04-I-0018

Active Accrual, Protocols Recruiting New Patients

Title:
Phase II/III Study Evaluating the Effect of IL-2 on Preservation of the CD4 T-Lymphocytes After Interruption of Anti-Retroviral Treatment in HIV Infected Patients with CD4 T-Lymphocyte Count Greater Than 500 Cells/mm(3) Who Have Received Anti-Retroviral T
Number:
04-I-0018
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.

Sponsoring Institute:
National Institute of Allergy and Infectious Diseases (NIAID)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): Children

Eligibility Criteria:
INCLUSION CRITERIA:

Age greater than or equal to 18 years.

HIV-1 infection confirmed by ELISA and Western Blot before W-2.

Category A or B HIV-1 infection.

Anti-retroviral treatment:

started at least 12 months prior to W-2;

stable and continuous for at least 12 weeks prior to W-2;

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 W-2 (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).

EXCLUSION CRITERIA:

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.

Acute infection in the 14 days preceding inclusion.

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.

Malignancy requiring chemotherapy.

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.

Special Instructions: Currently Not Provided
Keywords:
Lipodystrophy
Quality of Life
Treatment Interruption
HIV
Recruitment Keywords:
None
Conditions:
HIV Infections
Investigational Drug(s):
IL-2
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
Arno A, Ruiz L, et al. Efficacy of low-dose subcutaneous interleukin-2 to treat advanced human immunodeficiency virus type 1 in persons with

Carr A, Emery S, et al., 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. PMID: 9806026

Carr A, Cooper DA. Adverse effects of antiretroviral therapy. Lancet. 2000 Oct 21;356(9239):1423-30. Review. PMID: 11052597

Active Accrual, Protocols Recruiting New Patients

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