The purpose of this study is to compare the safety and effectiveness of fenofibrate and
pravastatin in treating HIV-positive patients who have abnormal levels of fat (lipids) in the
blood.
Increased lipids in the blood associated with HIV infection and anti-HIV drugs is a growing
problem. The drugs used in this study are known to reduce certain lipids, but little is known
about their safety and effectiveness. This study will see if one of the drugs is safer and
more effective than the other, or if combining the drugs is the safest and most effective way
to lower lipids. This study has been changed. On June 26, 2001, this study was reviewed by
the Data and Safety Monitoring Board (DSMB). The DSMB is an independent board monitoring the
progress of the study. The review showed that neither pravastatin nor fenofibrate alone were
effective in reaching all the cholesterol and triglyceride goals. There were no safety
concerns. It is not known if the combination of fenofibrate and pravastatin is effective and
safe. Therefore, it is important to continue this study.
Patients are randomized to either Arm A or Arm B and stratified by gender, TG level, and
number of cardiovascular risk factors. Patients add daily fenofibrate (Arm A) or pravastatin
(Arm B) to their antiretroviral therapy for 48 weeks. Evaluations at Week 12 determine LDL,
TG, and high-density lipid (HDL) levels. Patients who achieve clinical goals for these levels
stay on the drug for the rest of the study. Patients who do not achieve the goals by Week 12
receive a combination of pravastatin and fenofibrate for the rest of the study. At regular
clinic visits, patients have physical exams and are questioned about their medications, diet,
and exercise. Blood samples are drawn for clinical evaluations, including lipid profiles and
HIV-1 RNA monitoring. [AS PER AMENDMENT 12/13/01: On June 26, 2001, the DSMB reviewed
interim results and determined that the response rates for both arms met the stopping rule
for futility. As a result, all patients who were currently on single-agent therapy were
offered the opportunity to initiate dual-agent therapy regardless of time on study. No
additional accrual was sought; however, exceptions were made for patients who were in
screening at the time of the DSMB review. These patients were given the option of starting
single- or dual-agent therapy. The DSMB recommended that all patients on dual-agent therapy
be followed for 32 weeks to obtain additional safety and efficacy data. Further endpoints
will be analyzed after Week 12 of single-agent therapy or Week 32 of dual-agent therapy.]
Inclusion Criteria
Patients may be eligible for this study if they:
- Are HIV-positive.
- Are at least 18 years old.
- Are on a lipid-lowering diet based on the patient's statement and have been exercising
for at least 30 days before being screened for the study. Patients will be asked if
they were counseled by their health care provider. The lipid-lowering diet and
exercise program do not have to be prescribed by a physician.
- Have a triglyceride (TG) level of at least 200 mg/dl and low-density lipoprotein (LDL)
level of at least 130 mg/dl after fasting for 8 to 12 hours.
- Have been treated with anti-HIV drugs for more than 6 months. Patients must be taking
the anti-HIV drugs regularly for at least 4 weeks before they enter the study.
Patients must be taking anti-HIV drugs regularly for at least 8 weeks if they have
changed from taking protease inhibitor (PI) anti-HIV drugs to non-PI anti-HIV drugs.
Any combination without a PI must lower the patient's HIV viral levels, as determined
by the patient's physician.
- Are willing, if able to become pregnant, to use 2 reliable types of birth control
while taking the study drug(s) and for 1 month after stopping the drug(s).
- Have a negative pregnancy test.
- (This reflects a change in inclusion requirements.)
Exclusion Criteria
Patients will not be eligible for the study if they:
- Have a history of heart disease.
- Have uncontrolled high blood pressure within 4 weeks of study entry.
- Have liver disease.
- Have gall bladder disease or symptoms within 3 months prior to study entry or symptoms
of gallstones.
- Had surgery to remove their gallbladder within 3 months prior to study entry.
- Have diabetes requiring drug treatment or diabetes not controlled by diet.
- Have hypothyroidism (low thyroid activity).
- Are allergic or sensitive to the study drug(s) or to other lipid-lowering drugs.
- Have rhabdomyolysis (a muscle disease).
- Have taken any prescription or non-prescription lipid-lowering drug within 14 days
prior to study entry or for over 24 weeks in the past.
- Take prescription lipid-lowering agents, other than those given by the study, and
non-prescription lipid-lowering agents such as garlic supplements.
- Have failed previous statin or fibrate therapy (after 24 weeks of treatment) or have
had side effects from these drugs.
- Receive or have received (within 14 days of study entry) treatment not approved by the
FDA. Anti-HIV medications and immune-based treatments not approved by the FDA may be
allowed on a case-by-case basis with the approval of the protocol team.
- Were given systemic chemotherapy for cancer other than Kaposi's sarcoma (KS).
- Were given radiation therapy within 30 days of study entry.
- Take drugs that increase risk of muscle disease (such as cyclosporine, erythromycin,
itraconazole, and ketoconazole), within 14 days of study entry.
- Take or have taken levothyroxine and liothyronine for hypothyroidism.
- Take high doses of testosterone.
- Take creatine monophosphate or drugs that affect the immune system, within 30 days of
study entry.
- Abuse drugs or alcohol, and the doctor thinks this may interfere with the study.
- Are pregnant or breast-feeding.
- Had a scheduled anti-HIV treatment withdrawal prior to study entry.
- (This reflects a change in exclusion requirements.)
Univ of Puerto Rico, San Juan 009365067, Puerto Rico
Univ of Alabama at Birmingham, Birmingham, Alabama 35294, United States
Stanford Univ Med Ctr, Stanford, California 943055107, United States
UCLA CARE Ctr, Los Angeles, California 90095, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Harbor UCLA Med Ctr, Torrance, California 90502, United States
San Mateo AIDS Program / Stanford Univ, Stanford, California 943055107, United States
University of California San Francisco, San Francisco, California 941104206, United States
Willow Clinic, Menlo Park, California 94025, United States
Univ of California San Francisco, San Francisco, California 94110, United States
Univ of California, San Diego, San Diego, California 92103, United States
Univ of Colorado Health Sciences Ctr, Denver, Colorado 80262, United States
Denver Dept of Health and Hosps, Denver, Colorado 80262, United States
Univ of Miami School of Medicine, Miami, Florida 331361013, United States
Emory Univ, Atlanta, Georgia 30308, United States
Univ of Hawaii, Honolulu, Hawaii 96816, United States
Tripler Army Med Ctr, Tripler AMC, Hawaii 96859, United States
Northwestern Univ Med School, Chicago, Illinois 60611, United States
The CORE Ctr, Chicago, Illinois 60612, United States
Indiana Univ Hosp, Indianapolis, Indiana 462025250, United States
Methodist Hosp of Indiana / Life Care Clinic, Indianapolis, Indiana 46202, United States
Wishard Hosp, Indianapolis, Indiana 46202, United States
Johns Hopkins Hosp, Baltimore, Maryland 21287, United States
Harvard (Massachusetts Gen Hosp), Boston, Massachusetts 02114, United States
Beth Israel Deaconess - West Campus, Boston, Massachusetts 02215, United States
Boston Med Ctr, Boston, Massachusetts 02118, United States
Brigham and Women's Hosp, Boston, Massachusetts 02215, United States
Univ of Minnesota, Minneapolis, Minnesota 55455, United States
Univ of Nebraska Med Ctr, Omaha, Nebraska 681985130, United States
Univ of Rochester Medical Center, Rochester, New York 14642, United States
Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States
Mount Sinai Med Ctr, New York, New York 10029, United States
Cornell Univ Med Ctr, New York, New York 10021, United States
SUNY / Erie County Med Ctr at Buffalo, Buffalo, New York 14215, United States
Beth Israel Med Ctr, New York, New York 10003, United States
Columbia Presbyterian Med Ctr, New York, New York 10032, United States
St Mary's Hosp (Univ of Rochester/Infectious Diseases), Rochester, New York 14642, United States
Cornell Clinical Trials Unit - Chelsea Clinic, New York, New York 10011, United States
Community Health Network Inc, Rochester, New York 14642, United States
Carolinas Med Ctr, Charlotte, North Carolina 28203, United States
Univ of North Carolina, Chapel Hill, North Carolina 275997215, United States
Moses H Cone Memorial Hosp, Greensboro, North Carolina 27401, United States
Duke Univ Med Ctr, Durham, North Carolina 27710, United States
Case Western Reserve Univ, Cleveland, Ohio 44106, United States
Univ of Cincinnati, Cincinnati, Ohio 452670405, United States
Ohio State Univ Hosp Clinic, Columbus, Ohio 432101228, United States
MetroHealth Med Ctr, Cleveland, Ohio 441091998, United States
Univ of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Univ of Pennsylvania, Philadelphia, Pennsylvania 19104, United States
Philadelphia Veterans Administration Med Ctr, Philadelphia, Pennsylvania 19104, United States
Rhode Island Hosp / Brown Univ, Providence, Rhode Island 02903, United States
Miriam Hosp / Brown Univ, Providence, Rhode Island 02906, United States
Brown Univ / Miriam Hosp, Providence, Rhode Island 02906, United States
Julio Arroyo, West Columbia, South Carolina 29169, United States
Vanderbilt Univ Med Ctr, Nashville, Tennessee 37203, United States
Univ of Texas Galveston, Galveston, Texas 775550435, United States
Univ of Texas, Southwestern Med Ctr of Dallas, Dallas, Texas 75390, United States
Univ of Washington, Seattle, Washington 98104, United States
