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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Aldesleukin

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.

• Study Type: Interventional
• Enrollment: 104
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Alabama Therapeutics CRS
  • Colorado
    • Aurora, Colorado, United States, 80262
      • University of Colorado Hospital CRS
  • Indiana
    • Indianapolis, Indiana, United States, 462025250
      • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
  • New York
    • Buffalo, New York, United States, 14215
      • SUNY - Buffalo, Erie County Medical Ctr.
    • New York, New York, United States, 10016
      • NY Univ. HIV/AIDS CRS
    • New York, New York, United States, 10021
      • Cornell University A2201
    • New York, New York, United States, 10003
      • Beth Israel Med. Ctr. (Mt. Sinai)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 275997215
      • Unc Aids Crs
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Case CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hosp. of the Univ. of Pennsylvania CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Pomerantz R; Study Chair: Teppler H

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Completion (Actual): March 1, 2002

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Drug Therapy, Combination; AIDS-Related Complex; Antiviral Agents; Interleukin-2
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Communicable Diseases; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antineoplastic Agents; Aldesleukin
• Other Study ID Numbers: ACTG 248; 11225 (DAIDS ES Registry ID)