Effect of Interleukin-2 on HIV Treatment Interruption

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00015704
First received: May 1, 2001
Last updated: May 21, 2012
Last verified: May 2012
  Purpose

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.


Condition Intervention
HIV Infections
Drug: Aldesleukin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


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

Estimated Enrollment: 80
Study Completion Date: November 2004
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.

  Eligibility

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00015704

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

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00015704     History of Changes
Other Study ID Numbers: A5102, 10179
Study First Received: May 1, 2001
Last Updated: May 21, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Treatment Experienced
Treatment Interruption
Drug Administration Schedule
CD4 Lymphocyte Count
Anti-HIV Agents
Tetanus Toxoid
Aldesleukin
Diphtheria Toxoid

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Aldesleukin
Interleukin-2
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 30, 2014