Safety and Effectiveness of Fenofibrate and Pravastatin in HIV-Positive Patients With Abnormal Blood Lipids

Overview

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.

Lipid disorders associated with HIV infection and antiretroviral therapy are of growing concern. There is little information available on the safety and efficacy of statins or fibrates in the treatment of HIV-associated hyperlipidemias. Fenofibrate and pravastatin both are able to reduce low-density lipoproteins (LDL) and triglycerides (TG), but it is unclear whether one therapy will be more effective than the other, or if combination therapy will be needed to achieve desirable reductions in both LDL and TG. \[AS PER AMENDMENT 12/13/01: The NIAID HIV Therapeutic Trials Data and Safety Monitoring Board (DSMB) met June 26, 2001 to review the interim results. The interim monitoring plan for this study states that accrual into either single-agent therapy arm should stop if the response rate failed to meet a pre-specified minimum at the time of interim review. The DSMB found that this stopping criterion was met for each single-therapy arm. The DSMB recommended that patients currently on single-agent therapy be offered the opportunity to initiate dual-agent therapy, regardless of time on study. There were no safety concerns.\] 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. \[AS PER AMENDMENT 12/13/01: On June 26, 2001, the DSMB reviewed interim results and determined that the response rates for both arms met the stopping rule for futility. As a result, all patients who were currently on single-agent therapy were offered the opportunity to initiate dual-agent therapy regardless of time on study. No additional accrual was sought; however, exceptions were made for patients who were in screening at the time of the DSMB review. These patients were given the option of starting single- or dual-agent therapy. The DSMB recommended that all patients on dual-agent therapy be followed for 32 weeks to obtain additional safety and efficacy data. Further endpoints will be analyzed after Week 12 of single-agent therapy or Week 32 of dual-agent therapy.\]