A Study to Evaluate the Ability of TNFR:Fc to Decrease the Amount of IL-6 (Interleukin-6) and TNF-Alpha (Tumor Necrosis Factor) in HIV-Infected Patients - Full Text View

Purpose

The purpose of this study is to determine if TNFR:Fc (a molecule that attaches to TNF) can lower the amount of IL-6 in HIV-positive patients. This study will also examine the effect of TNFR:Fc on TNF-alpha. IL-6 and TNF-alpha are 2 substances produced by the immune system that may increase the rate of HIV replication.

IL-6 and TNF-alpha are produced naturally by the body. High levels of TNF-alpha lead to increased IL-6 production and increased HIV replication, therefore helping the virus infect the body. HIV-positive patients who receive IL-2 (interleukin-2, a protein that helps the immune system fight infection) tend to have higher levels of IL-6 and TNF-alpha than patients not receiving IL-2. These increased levels may contribute to some of the flu-like symptoms related to IL-2 administration. TNFR:Fc can neutralize TNF-alpha to decrease the action of TNF-alpha and, in turn, decrease the amount of IL-6 in the body. TNFR:Fc may, therefore, have a role in the treatment of HIV disease or in relieving some of the symptoms related to IL-2 administration.

Condition	Intervention
HIV Infections	Drug: Tumor Necrosis Factor soluble receptor-immunoadhesin complex

MedlinePlus related topics:

AIDS Cancer

ChemIDplus related topics:

Interleukin-2 Tumor Necrosis Factors

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Safety Study

Official Title:	Effect of Recombinant Human Soluble Tumor Necrosis Factor Receptor (TNFR:Fc) on Interleukin-6 (IL-6), Tumor Necrosis Factor-Alpha (TNF-Alpha) and Markers of Immune Activation in HIV-Infected Subjects

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment:

18

Detailed Description:

Both Interleukin-6 (IL-6) and Tumor necrosis factor-alpha (TNF-alpha) are substances naturally produced by the body's immune system. Evidence suggests that TNF-alpha production may be excessive or inappropriate in HIV-infected patients. Elevated TNF-alpha levels can result in increased IL-6 production and possibly increased HIV replication. TNFR:Fc is a modification of a natural substance that binds to TNF-alpha and neutralizes its activity. It is postulated that TNFR:Fc may result in decreased activity of TNF-alpha and lower IL-6 levels. HIV-infected patients who receive Interleukin-2 (IL-2) have been shown to have higher TNF-alpha and IL-6 levels than those who do not receive IL-2. It is thought that these higher levels of TNF-alpha and IL-6 may contribute to some of the flu-like symptoms experienced by patients receiving IL-2. By decreasing the amount of IL-6 in the body and by decreasing the action of TNF-alpha in the body, TNFR:Fc may have a role in the treatment of HIV disease or in alleviating some of the symptoms related to IL-2 administration.

Six patients from each of the 3 treatment arms of ACTG 328 (HAART alone, HAART plus intravenous (IV) rhIL-2, and HAART plus subcutaneous (SC) rhIL-2) who are about to be randomized to Step II of ACTG 328 may participate in this prospective, nested substudy. Patients randomized to the Interleukin-2 (IL-2) arms of ACTG 328 are pretreated with TNFR:Fc (administered by infusion over 30 minutes) at week 16 of ACTG 928 (Course 3, Week 28 of ACTG 328), just prior to initiation of IL-2. Those randomized to the highly active antiretroviral therapy (HAART) only arm of ACTG 328 receive treatment with TNFR:Fc at Week 16 of ACTG 928 (Week 28 of ACTG 328).

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

You may be eligible for this study if you:

Are HIV-positive.
Are enrolled in ACTG 328.
Agree to practice abstinence or use barrier methods of birth control during the study.
Are at least 18 years old.

Exclusion Criteria

You will not be eligible for this study if you:

Have any active opportunistic (HIV-associated) infections.
Have any medical condition or psychological issue that would interfere with study requirements.
Are pregnant or breast-feeding.
Are receiving any experimental drug other than IL-2.
Are receiving certain other medications.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001116

Locations


United States, Colorado
	Univ of Colorado Health Sciences Ctr
	Denver, Colorado, United States, 80262

United States, Hawaii
	Univ of Hawaii
	Honolulu, Hawaii, United States, 96816

United States, New York
	Bellevue Hosp / New York Univ Med Ctr
	New York, New York, United States, 10016
	Mount Sinai Med Ctr
	New York, New York, United States, 10029

United States, Ohio
	Case Western Reserve Univ
	Cleveland, Ohio, United States, 44106

United States, Texas
	Univ of Texas Galveston
	Galveston, Texas, United States, 775550435

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Study Chair:	Sha B

Study Chair:	Valdez H

Study Chair:	Landay A

Study Chair:	Lederman M

More Information

Publications:

Lange CG, Valdez H, Medvik K, Asaad R, Lederman MM. CD4+ T-lymphocyte nadir and the effect of highly active antiretroviral therapy on phenotypic and functional immune restoration in HIV-1 infection. Clin Immunol. 2002 Feb;102(2):154-61.

Sha B, Valdez H, Landay A, Gelman R, Namkung A, Agosti J, Bancroft L, Mildvan D, Mitsuyasu R, Pollard R, Ogata-Arakaki D, Kilgo P, Estep S, Fox L, Lederman M. Effect of recombinant human soluble tumor necrosis factor receptor (TNFR, etanercept) on interleukin-6 (IL- 6), TNF-a, and markers of immune activation in HIV-infected subjects receiving interleukin-2 (IL-2). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 66)

Sha BE, Valdez H, Gelman RS, Landay AL, Agosti J, Mitsuyasu R, Pollard RB, Mildvan D, Namkung A, Ogata-Arakaki DM, Fox L, Estep S, Erice A, Kilgo P, Walker RE, Bancroft L, Lederman MM. Effect of etanercept (Enbrel) on interleukin 6, tumor necrosis factor alpha, and markers of immune activation in HIV-infected subjects receiving interleukin 2. AIDS Res Hum Retroviruses. 2002 Jun 10;18(9):661-5.

Study ID Numbers:	ACTG 928
First Received:	November 2, 1999
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00001116
Health Authority:	United States: Federal Government

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

Tumor Necrosis Factor

Interleukin-2

Immunity, Cellular

Antiviral Agents

Interleukin-6

Receptors, Tumor Necrosis Factor

Study placed in the following topic categories:

Virus Diseases

Sexually Transmitted Diseases, Viral

Necrosis

Interleukin-2

HIV Infections

Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome

TNFR-Fc fusion protein

Retroviridae Infections

Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Anti-Inflammatory Agents

RNA Virus Infections

Slow Virus Diseases

Immunologic Factors

Immune System Diseases

Physiological Effects of Drugs

Gastrointestinal Agents

Infection

Immunosuppressive Agents

Pharmacologic Actions

Pathologic Processes

Analgesics, Non-Narcotic

Sensory System Agents

Therapeutic Uses

Lentivirus Infections

Anti-Inflammatory Agents, Non-Steroidal

Analgesics

Peripheral Nervous System Agents

Antirheumatic Agents

Central Nervous System Agents

ClinicalTrials.gov processed this record on September 04, 2008

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00001116