Treatment with pravastatin and fenofibrate improves atherogenic lipid profiles but not inflammatory markers in ACTG 5087

Abstract

Objectives: Statins and fibrates alter lipids, apolipoproteins and inflammatory markers in persons without HIV. The objective of this study was to evaluate changes in lipoproteins, apolipoproteins and other markers of inflammation with the use of pravastatin and fenofibrate.

Design: Evaluation of participants in ACTG A5087, a randomized trial of pravastatin 40 mg/day or fenofibrate 200 mg/day for the treatment of dyslipidemia. Participants that failed single-agent therapy at week 12 were given the combination.

Methods: Participants with available specimens were tested for apolipoproteins A1 and B, adiponectin, plasminogen-activator inhibitor type 1 (PAI-1), P-selectin, and high-sensitivity C-reactive protein (hs-CRP).

Results: 74 participants (37 per randomized arm) received either pravastatin or fenofibrate for 12 weeks with 60 receiving combination treatment from weeks 12-48. There were no significant changes in hs-CRP, PAI-1, and P-selectin. From baseline to week 12, the median Apo B levels (-8 mg/dL, P=0.01 for fenofibrate and -27 mg/dL, P<0.01 for pravastatin) and ApoB/A1 ratios (-0.16, P<0.01 for both arms) significantly decreased. From baseline to week 48, median adiponectin (-1 ng/dL, P<0.01), Apo B (-22 mg/dL, P<0.01) and Apo B/A1 ratios (-0.2, P<0.01) all decreased in those who went on combination therapy, whereas Apo A1 (9.5 mg/dL, P=0.01) levels increased.

Conclusion: Treatment with pravastatin or fenofibrate improves the atherogenic lipid profile within the first 12 weeks and is sustained through 48 weeks with combination therapy. Adiponectin levels decrease with lipid-lowering therapy. However, markers of inflammation and platelet activation were not appreciably changed suggesting that the biologic properties of these agents differ in persons with HIV infection.

Keywords: Antiretroviral therapy; Apolipoproteins; Dyslipidemia; Fenofibrate; HIV; Inflammation; Lipoproteins; Pravastatin.

Conflict of interest statement

Conflicts of Interest: Drs. Evans and Yeh have no conflicts to report. Dr. Fichtenbaum received funding for a research grant to his institution from Abbott Pharmaceuticals. Dr. Aberg has participated in advisory boards for Abbott Pharmaceuticals and Bristol Meyers Squibb.

Figures

Figure 1. Diagram of Participants Included in Analysis

71 participants were missing or had an inadequate volume of blood samples at baseline, week 12 or week 48 and were excluded. There were 49 participants randomized to fenofibrate and 53 randomized to pravastatin that were eligible to participate in this study. To obtain the sample size of 37 participants per arm, every other subject with adequate samples was excluded until we reached 37 participants in Arm A and Arm B.