Increasing HAART-Induced Immune Restoration With Cyclosporine
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Abacavir sulfate, Lamivudine and Zidovudine (Drug); Cyclosporine (Drug); Hepatitis A Vaccine (Inactivated) (Biological); Efavirenz (Drug); Pneumococcal Conjugate Vaccine, Heptavalent (Biological); Rabies Vaccine (Biological)
Phase: Phase 2
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s):
Michael Lederman, M.D., Study Chair, Affiliation: Case Western Reserve University
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.
Clinical Details
Official title: Augmenting the Magnitude of HAART-Induced Immune Restoration With the Use of Cyclosporine
Study design: Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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).
Locations and Contacts
University of California , Davis Medical Center, Sacramento, California 95814, United States
University of Miami, Miami, Florida 33136-1013, United States
Rush Presbyterian - Saint Luke's Med Ctr, Chicago, Illinois 60612, United States
Rush Presbyterian - Saint Luke's Med Ctr / Infect Dis, Chicago, Illinois 606123832, United States
Indiana University Hospital, Indianapolis, Indiana 46202-5250, United States
University of Maryland, Institute of Human Virology, Baltimore, Maryland 21201, United States
Univ of Minnesota, Minneapolis, Minnesota 55455-0392, United States
Washington Univ (St. Louis), St. Louis, Missouri 63108, United States
Univ of North Carolina / Infectious Disease Division, Chapel Hill, North Carolina 27599, United States
Univ of North Carolina, Chapel Hill, North Carolina 27599-7215, United States
Case Western Reserve Univ, Cleveland, Ohio 44106, United States
MetroHealth Med Ctr, Cleveland, Ohio 441091998, United States
University of Pennsylvania, Philadelphia, Philadelphia, Pennsylvania 19104, United States
University of Pennsylvania, Philadelphia, Philadelphia, Pennsylvania 19104, United States
Univ of Texas, Southwestern Med Ctr of Dallas, Dallas, Texas 75390, United States
Univ of Texas Southwestern Med Ctr, Dallas, Texas 75390, United States
Additional Information
Click here for more information about Efavirenz Click here for more information about Abacavir sulfate, Lamivudine and Zidovudine Haga clic aquí para ver información sobre este ensayo clínico en español.
Last updated: August 3, 2006
|
