Effect of Interleukin-2 on HIV Treatment Interruption

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

An Open-Label, Pilot Study Utilizing CD4 T-Cell Counts Lower Than 350 Cells/mm3 as the Threshold for Restarting Therapy With Potent Antiretroviral Therapy With or Without Interleukin-2 to Determine the Effect of Pulse Therapy on the Characteristics of Treatment Interruptions

Interleukin-2 (IL-2) helps the body make infection-fighting white blood cells, including CD4 and CD8 T cells. One HIV treatment strategy is planned treatment interruption (stopping anti-HIV drugs when CD4 count and level of virus in the blood are at certain levels). The purpose of this study is to see if IL-2 used with potent anti-HIV drugs allows for longer HIV treatment interruptions.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

One approach in reconstituting an HIV-diminished immune system is the use of potent antiretroviral therapy (ART) in conjunction with IL-2. IL-2 is a cytokine secreted by activated T cells that regulates the proliferation and differentiation of CD4 and CD8 T cells. Although treatment with IL-2 can cause temporary increases in HIV viral load, clinical studies with IL-2 have revealed no long-term adverse effects on viral load. IL-2 therapy may also help purge the host's latent viral reservoir through activation of resting lymphocytes harboring provirus. Another approach to managing HIV infection is strategic treatment interruption. Results from small pilot trials suggest that HIV replication can be highly suppressed over consecutive courses of ART following short treatment interruptions, and CD4 T cell counts can be maintained on these interruptions with some positive effect on HIV-specific immunity. This study will evaluate potent ART, started and interrupted based on CD4 cell counts, with or without IL-2.

Patients will be stratified based on lifetime CD4 T-cell nadir (lowest measurement) into one of three groups. Group 1 will have a nadir of 200 CD4 cells/mm3; Group 2 will have a nadir greater than 200 CD4 cells/mm3; and patients with no documented nadir count available will join Group 3. Within each group, patients will be randomly assigned to one of two study arms. Arm A patients will receive pulses of potent ART with IL-2, while Arm B patients will receive pulses of potent ART alone. Patients in Arm A will receive potent ART with IL-2 given by subcutaneous injection twice daily for 5 days every 8 weeks for at least 17 weeks. Arm B patients will receive potent ART alone for at least 17 weeks. Both groups then go on treatment interruption for approximately 64 weeks, followed by potent ART alone for an additional 24 weeks. Patients will repeat this cycle of potent ART with or without IL-2, treatment interruption, and potent ART alone throughout the study. This study will last approximately 4 years.

Clinical and laboratory assessments will be performed periodically throughout the study. CD4 T cell counts and viral load will determine if a patient can enter the next treatment step. Potent ART is not provided by this study.

A5109s is a limited-center substudy designed to determine whether viral replication impairs lymphocyte proliferation in vivo. Patients at substudy-participating sites will register to the substudy immediately after beginning their first treatment interruption in the main study.

Study Type

Interventional

Enrollment

80

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States
        • UCLA CARE Center CRS
      • Palo Alto, California, United States, 943055107
        • Stanford CRS
      • San Jose, California, United States
        • Santa Clara Valley Med. Ctr.
      • San Mateo, California, United States, 943055107
        • San Mateo County AIDS Program
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush Univ. Med. Ctr. ACTG CRS
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • University of Minnesota, ACTU
    • Missouri
      • Saint Louis, Missouri, United States
        • St. Louis ConnectCare, Infectious Diseases Clinic
      • Saint Louis, Missouri, United States, 63108
        • Washington U CRS
    • Nebraska
      • Omaha, Nebraska, United States, 681985130
        • Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
    • New York
      • New York, New York, United States, 10003
        • Beth Israel Med. Ctr., ACTU
      • New York, New York, United States
        • Weill Med. College of Cornell Univ., The Cornell CTU
      • New York, New York, United States, 10021
        • Cornell CRS
    • North Carolina
      • Chapel Hill, North Carolina, United States
        • Unc Aids Crs
      • Durham, North Carolina, United States, 27710
        • Duke Univ. Med. Ctr. Adult CRS
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case CRS
      • Cleveland, Ohio, United States, 441091998
        • MetroHealth CRS
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • Pitt CRS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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:

  • HIV infected
  • On stable, potent ART regimen for at least 3 months prior to study entry
  • Viral load of less than 400 copies/ml for at least 6 months prior to study entry
  • Viral load of less than 200 copies/ml at screening
  • CD4 count of 500 cells/mm3 or greater at screening
  • Agree to use acceptable methods of contraception
  • Agree to be followed on this study for at least 4 years
  • Primary care provider willing to have the patient in the study and to comply with study guidelines

Exclusion Criteria:

  • Active or past significant AIDS-related illness. Patients with a history of minimal (less than 10 lesions) cutaneous Kaposi's sarcoma, pulmonary tuberculosis, or bacterial pneumonia are not excluded.
  • Immunomodulators within 1 month of study entry
  • Hydroxyurea within 3 months of study entry
  • Prior IL-2 treatment
  • Drugs to treat heart disease within 30 days of study entry
  • Serious heart problems
  • Cancer requiring anti-cancer drugs
  • Thyroid problems. If the condition has been controlled by drugs for at least 3 months prior to study entry, the patient is not excluded.
  • Uncontrolled diabetes
  • Breathing or stomach problems that, in the opinion of the investigator, may affect the safety of the patient
  • History of autoimmune disease, including inflammatory bowel disease, psoriasis, and optic neuritis
  • Organ transplant
  • History of neurological disorder or mental illness that, in the opinion of the investigator, may interfere with study requirements
  • Alcohol or drug abuse that, in the opinion of the investigator, may interfere with study requirements
  • Astemizole, midazolam, or triazolam within 2 weeks of study entry
  • Systemic corticosteroids for 4 weeks or more within 3 months of study entry
  • Pregnancy or breastfeeding

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: W. Keith Henry, MD, HIV Program, Hennepin County Medical Center, University of Minnesota

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

November 1, 2004

Study Registration Dates

First Submitted

May 1, 2001

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 1, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A5102
  • 10179 (Registry Identifier: DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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