Treatment With Pravastatin and Fenofibrate Improves Atherogenic Lipid Profiles but Not Inflammatory Markers in ACTG 5087

J Clin Lipidol. Jul-Aug 2010;4(4):279-87. doi: 10.1016/j.jacl.2010.04.003.

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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adiponectin / blood
  • Adult
  • Aged
  • Anti-Retroviral Agents / therapeutic use
  • Anticholesteremic Agents / therapeutic use*
  • Apolipoproteins A / blood
  • Apolipoproteins B / blood
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Drug Administration Schedule
  • Dyslipidemias / complications
  • Dyslipidemias / drug therapy*
  • Female
  • Fenofibrate / therapeutic use*
  • HIV Infections / complications
  • HIV Infections / diagnosis
  • HIV Infections / drug therapy
  • Humans
  • Male
  • Middle Aged
  • P-Selectin / blood
  • Plasminogen Activator Inhibitor 1 / blood
  • Pravastatin / therapeutic use*
  • RNA, Viral / blood

Substances

  • Adiponectin
  • Anti-Retroviral Agents
  • Anticholesteremic Agents
  • Apolipoproteins A
  • Apolipoproteins B
  • Biomarkers
  • P-Selectin
  • Plasminogen Activator Inhibitor 1
  • RNA, Viral
  • C-Reactive Protein
  • Pravastatin
  • Fenofibrate