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Increasing HAART-Induced Immune Restoration With Cyclosporine

This study has been completed.
Sponsor:
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00031070
First received: February 20, 2002
Last updated: December 19, 2008
Last verified: August 2006
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Abacavir sulfate, Lamivudine and Zidovudine
Drug: Cyclosporine
Biological: Hepatitis A Vaccine (Inactivated)
Drug: Efavirenz
Biological: Pneumococcal Conjugate Vaccine, Heptavalent
Biological: Rabies Vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Augmenting the Magnitude of HAART-Induced Immune Restoration With the Use of Cyclosporine

Resource links provided by NLM:


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

Estimated Enrollment: 40
Study Completion Date: December 2006
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.

  Eligibility

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

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).
  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: NCT00031070

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

Additional Information:
No publications provided by National Institute of Allergy and Infectious Diseases (NIAID)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00031070     History of Changes
Other Study ID Numbers: ACTG A5138, AACTG A5138, ACTG A5139s, AACTG A5139s
Study First Received: February 20, 2002
Last Updated: December 19, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Zidovudine
CD4 Lymphocyte Count
Lamivudine
Cyclosporine
Hepatitis A Vaccine
Rabies Vaccine
abacavir
Antiretroviral Therapy, Highly Active
efavirenz
Treatment Naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
RNA Virus Infections
Retroviridae Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Abacavir
Cyclosporine
Cyclosporins
Efavirenz
Lamivudine
Lamivudine, zidovudine drug combination
Zidovudine
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antifungal Agents
Antimetabolites
Antirheumatic Agents
Antiviral Agents
Dermatologic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on November 27, 2014