COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu

Increasing HAART-Induced Immune Restoration With Cyclosporine

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00031070
Recruitment Status : Completed
First Posted : February 22, 2002
Last Update Posted : March 9, 2015
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
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 or disease Intervention/treatment 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

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Augmenting the Magnitude of HAART-Induced Immune Restoration With the Use of Cyclosporine
Actual Study Completion Date : December 2006

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00031070

Layout table for location information
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
National Institute of Allergy and Infectious Diseases (NIAID)
Layout table for investigator information
Study Chair: Michael Lederman, M.D. Case Western Reserve University

Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00031070    
Other Study ID Numbers: ACTG A5138
ACTG A5139s
AACTG A5139s
First Posted: February 22, 2002    Key Record Dates
Last Update Posted: March 9, 2015
Last Verified: August 2006
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
CD4 Lymphocyte Count
Hepatitis A Vaccine
Rabies Vaccine
Antiretroviral Therapy, Highly Active
Treatment Naive
Additional relevant MeSH terms:
Layout table for MeSH terms
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Heptavalent Pneumococcal Conjugate Vaccine
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Anti-Retroviral Agents