A Phase II Study of Low-Dose Interleukin-2 by Subcutaneous Injection in Combination With Antiretroviral Therapy Versus Antiretroviral Therapy Alone in Patients With HIV-1 Infection and at Least 3 Months Stable Antiretroviral Therapy

NCT ID: NCT00000820

Last Updated: 2021-10-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 2002-03-31

Brief Summary

PRIMARY: To examine the effect of aldesleukin ( IL-2 ) on viral activity in the blood. To determine the safety of low-dose IL-2 in combination with antiretroviral therapy versus antiretroviral therapy alone.

SECONDARY: To examine delayed type hypersensitivity responses to skin test antigens and antibody responses to protein and polysaccharide vaccines.

The profound immune impairment that results from HIV-1 infection is due, at least in part, to the loss of CD4+ T cells and the cytokines these cells secrete, especially IL-2 and interferon-gamma. Antiretroviral agents do not directly address the problem of immune impairment. Replacement of IL-2 at nontoxic doses may prevent or delay clinical immunosuppression and its attendant opportunistic infections. Also, since patients with HIV-1 infection respond suboptimally to routine protein and polysaccharide immunizations, IL-2 may provide an adjuvant effect on vaccine responses.

Detailed Description

The profound immune impairment that results from HIV-1 infection is due, at least in part, to the loss of CD4+ T cells and the cytokines these cells secrete, especially IL-2 and interferon-gamma. Antiretroviral agents do not directly address the problem of immune impairment. Replacement of IL-2 at nontoxic doses may prevent or delay clinical immunosuppression and its attendant opportunistic infections. Also, since patients with HIV-1 infection respond suboptimally to routine protein and polysaccharide immunizations, IL-2 may provide an adjuvant effect on vaccine responses.

Patients are randomized initially to receive their own antiretroviral therapy alone or in combination with IL-2 for 24 weeks, after which each group is crossed over to the other treatment assignment (i.e., IL-2 is either added or deleted from the regimen) for an additional 24 weeks. Patients who are vaccine eligible receive influenza, tetanus and diphtheria toxoid, and meningococcal polysaccharide vaccines at week 4, and those who have not received pneumococcal vaccine prior to study entry will receive it at week 8.

Conditions

HIV Infections

Keywords

Interleukin-2; Drug Therapy, Combination; AIDS-Related Complex; Antiviral Agents

Study Design

• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT

Interventions

Aldesleukin

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• PCP prophylaxis.
• Therapy for an opportunistic infection that develops on study, with the exception of foscarnet for CMV disease or resistant Herpes simplex.
• Systemic corticosteroids ONLY IF given for no longer than 21 days for acute PCP.
• Topical corticosteroids to areas separate from a skin test or IL-2 injection site.
• Acyclovir up to 1000 mg/day as maintenance for recurrent genital Herpes.
• Erythropoietin and filgrastim.
• Antiemetics.
• Antibiotics as clinically indicated.
• Elective standard immunizations at week 8 or later.

Concurrent Treatment:

Allowed:

• Local radiation therapy.

Prior Medication: Required:

• Stable, approved antiretroviral therapy for at least 2 months (was 3 months, amended 3/26/96) prior to study entry.

Patients must have:

• HIV seropositivity.
• CD4 count 300 - 700 cells/mm3.
• Stable antiretroviral therapy for at least 2 months (was 3 months, amended 3/26/96) prior to study entry.
• No history of AIDS-defining illness except for limited cutaneous Kaposi's sarcoma.
• Normal EKG (isolated nonspecific ST and T wave changes permitted).

NOTE:

• This protocol is approved for prisoner participation.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Malignancy requiring systemic or local cytotoxic chemotherapy.
• Untreated thyroid disease.
• Asthma requiring intermittent or chronic inhalation or systemic therapy.
• Any medical condition that precludes study entry.

Concurrent Medication:

Excluded:

• Antianginal agents such as nitrates, calcium channel blockers, beta blockers, and antiarrhythmics.
• Systemic or local cytotoxic chemotherapy.
• Interferons.
• Interleukins other than study drug.
• Pentoxifylline ( Trental ).
• Acetylcysteine ( NAC ).
• Sargramostim ( GM-CSF ).
• Dinitrochlorobenzene ( DCNB ).
• Thymosin alpha 1.
• Thymopentin.
• Inosiplex ( Isoprinosine ).
• Polyribonucleoside ( Ampligen ).
• Ditiocarb sodium ( Imuthiol ).
• Therapeutic HIV vaccines.
• Investigational antiretroviral agents such as lamivudine ( 3TC ) and tat and protease inhibitors.
• Foscarnet.
• Aspirin.
• Immune globulin ( IVIG ).
• Thalidomide.
• Systemic corticosteroids (permitted for 21 days or less for PCP treatment only).

Concurrent Treatment:

Excluded:

• Ongoing transfusion.

Patients with the following prior conditions are excluded:

• History of autoimmune disease, including inflammatory bowel disease and psoriasis (although autoimmune thyroid disease that is stable is allowed).
• Clinically significant CNS disease or seizures that have been active within 1 year prior to study entry.

Prior Medication:

Excluded:

• IL-2 within 3 months prior to study entry.
• Any immunomodulatory therapy within 4 weeks prior to study entry.
• Foscarnet within 4 weeks prior to study entry.
• Acute therapy for an opportunistic infection within 14 days prior to study entry.

Active alcohol or substance abuse that would compromise study compliance.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Teppler H

Role: STUDY_CHAIR

Pomerantz R

Role: STUDY_CHAIR

Locations

Alabama Therapeutics CRS

Birmingham, Alabama, United States

University of Colorado Hospital CRS

Aurora, Colorado, United States

Indiana Univ. School of Medicine, Infectious Disease Research Clinic

Indianapolis, Indiana, United States

SUNY - Buffalo, Erie County Medical Ctr.

Buffalo, New York, United States

Beth Israel Med. Ctr. (Mt. Sinai)

New York, New York, United States

NY Univ. HIV/AIDS CRS

New York, New York, United States

Cornell University A2201

New York, New York, United States

Unc Aids Crs

Chapel Hill, North Carolina, United States

Case CRS

Cleveland, Ohio, United States

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, United States

Countries

United States

References

Vogler MA, Teppler H, Gelman R, Valentine F, Lederman MM, Pomerantz RJ, Pollard RB, Cherng DW, Gonzalez CJ, Squires KE, Frank I, Mildvan D, Mahon LF, Schock B; AIDS Clinical Trials Group 248 Study Team. Daily low-dose subcutaneous interleukin-2 added to single- or dual-nucleoside therapy in HIV infection does not protect against CD4+ T-cell decline or improve other indices of immune function: results of a randomized controlled clinical trial (ACTG 248). J Acquir Immune Defic Syndr. 2004 May 1;36(1):576-87. doi: 10.1097/00126334-200405010-00005.

Reference Type: BACKGROUND

PMID: 15097300 (View on PubMed)

Other Identifiers

11225

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 248

Identifier Type: -

Identifier Source: org_study_id