Increasing HAART-Induced Immune Restoration With Cyclosporine

March 5, 2015 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Augmenting the Magnitude of HAART-Induced Immune Restoration With the Use of Cyclosporine

The purpose of this study is to see if cyclosporine, taken when a patient begins highly active antiretroviral therapy (HAART), increases the number of CD4 T-cells (blood cells that fight infection) in a patient's blood. This study also will explore the safety of briefly giving cyclosporine to patients starting HAART.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The availability of HAART has substantially decreased the morbidity and mortality caused by HIV-1 infection. There is clinical and laboratory evidence suggesting that treatment of HIV-1 infection not only arrests the progressive immune deterioration caused by HIV-1, but also is associated with at least partial immune reconstitution. After starting HAART, most patients with chronic HIV-1 infection experience an increase in CD4 T-cells, but the magnitude of CD4 lymphocyte rise is highly variable. Patients who do not experience a substantial rise in circulating CD4 lymphocytes remain at risk for opportunistic infections. Strategies to enhance immune restoration in HIV-1 disease are needed. Studies have shown that immune restoration after HAART in patients with chronic HIV-1 infection is incomplete. There are, however, several potential methods that can be used that possibly may enhance the magnitude of CD4 lymphocyte rise induced by HAART. It is proposed that the lymphoid tissues, in which lymphocytes are trapped and activated to die, are a major site of immunopathology and cellular losses in HIV-infection. Interference with lymphocyte trapping and death in lymphoid tissues when cyclosporine, an immunosuppressant, is administered at the time of initiation of HAART may result in an enhancement of the magnitude of cellular restoration in patients who initiate HAART.

Patients are randomized to 1 of 2 treatment arms:

Arm A: Weeks 1 to 2: abacavir (ABC)/lamivudine (3TC)/zidovudine (ZDV). Weeks 3 to 48: ABC/3TC/ZDV and efavirenz (EFV).

Arm B: Weeks 1 to 2: ABC/3TC/ZDV and cyclosporine. Weeks 3 to 48: ABC/3TC/ZDV and EFV.

Patients in both arms receive the following immunizations: Weeks 8 and 12: Hepatitis A vaccine inactivated and rabies vaccine.

Week 16: Rabies vaccine. To ascertain whether the augmentation in the rise in CD4 lymphocytes is sustained, the number of circulating CD4 lymphocytes 48 weeks after starting therapy is compared. To examine the functional significance of the cellular increases, the ability of patients to respond to immunization with recall and neoantigens are compared between the cyclosporine plus HAART arm and the HAART alone arm.

Substudy A5139: A 2-week substudy designed to explore the mechanisms of first-phase cellular restoration is performed. Patients undergo 4 lymph node aspirates. Lymphocytes are analyzed by the use of flow cytometry and correlated with findings in the main study. There is no limit on patient enrollment. Patients register to the substudy immediately after randomizing to the main study.

Study Type

Interventional

Enrollment

40

Phase

  • Phase 2

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
      • Sacramento, California, United States, 95814
        • University of California , Davis Medical Center
    • Florida
      • Miami, Florida, United States, 33136-1013
        • University of Miami
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Rush Presbyterian - Saint Luke's Med Ctr
      • Chicago, Illinois, United States, 606123832
        • Rush Presbyterian - Saint Luke's Med Ctr / Infect Dis
    • Indiana
      • Indianapolis, Indiana, United States, 46202-5250
        • Indiana University Hospital
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland, Institute of Human Virology
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455-0392
        • Univ of Minnesota
    • Missouri
      • St. Louis, Missouri, United States, 63108
        • Washington Univ (St. Louis)
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Univ of North Carolina / Infectious Disease Division
      • Chapel Hill, North Carolina, United States, 27599-7215
        • Univ of North Carolina
    • Ohio
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve Univ
      • Cleveland, Ohio, United States, 441091998
        • MetroHealth Med Ctr
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania, Philadelphia
    • Texas
      • Dallas, Texas, United States, 75390
        • Univ of Texas, Southwestern Med Ctr of Dallas
      • Dallas, Texas, United States, 75390
        • Univ of Texas Southwestern Med Ctr

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

Patients may be eligible for this study if they:

  • Are HIV infected.
  • Have received no more than 7 days of any anti-HIV treatment prior to study entry and not within 3 weeks of study entry.
  • Have a CD4 cell count greater than 100 cells/mm3 within 30 days prior to study entry.
  • Have a viral load greater than 5000 copies/ml within 30 days prior to study entry.
  • Agree not to become pregnant or to impregnate during the study. The female/male partners must use 2 acceptable methods of contraception while receiving drugs and for 6 weeks after stopping the study drugs. Women and men who cannot have children do not need to use contraception.

Exclusion Criteria

Patients may not be eligible for this study if they:

  • Have an AIDS-related infection or abnormal tissue growth within 1 year of study entry.
  • Are pregnant or breast-feeding.
  • Weigh less than 88 lbs (40 kg).
  • Have taken 3TC or nonnucleoside reverse transcriptase inhibitors (NNRTIs).
  • Have continuously taken for longer than 3 days any of the following prohibited drugs within 14 days before study entry: angiotensin-converting inhibitors, antibiotics, anticonvulsants, antihistamines, antineoplastics, antifungals, anti-inflammatory drugs, benzodiazepines, calcium channel blockers, gastrointestinal agents, systemic glucocorticoids, immunosuppressives, immunomodulators, potassium-sparing diuretics, statins, allopurinol, amiodarone, bromocryptine, danazol, digoxin, methotrexate, metoclopramide, octreotide, ticlopidine, orlistat, pimozide, nefazodone, fluvoxamine, and ergot derivatives.
  • Have taken St. John's wort, grapefruit, or grapefruit juice continuously for longer than 3 days within 14 days before study entry.
  • Are allergic or sensitive to study HAART or cyclosporine.
  • Abuse drugs or alcohol.
  • Have autoimmune disease requiring immunosuppression.
  • Have kidney disease or insufficiency.
  • Have uncontrolled hypertension.
  • Have migraines that require current continuous use of drugs.
  • Have a seizure disorder that requires continuous use of anti-seizure drugs.
  • Have an HLA B-57 haplotype (this gene has been associated with an increased chance for developing an allergic reaction to ABC).

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: Michael Lederman, M.D., Case Western Reserve University

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)

December 1, 2006

Study Registration Dates

First Submitted

February 20, 2002

First Submitted That Met QC Criteria

February 21, 2002

First Posted (Estimate)

February 22, 2002

Study Record Updates

Last Update Posted (Estimate)

March 9, 2015

Last Update Submitted That Met QC Criteria

March 5, 2015

Last Verified

August 1, 2006

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG A5138
  • AACTG A5138
  • ACTG A5139s
  • AACTG A5139s

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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