Background:  Atherosclerosis is a complex inflammatory process. Treatment of dyslipidemia with statins or fibrates alters lipids and markers of inflammation however there are few published studies in persons with HIV. The objective of this study was to evaluate changes in apolipoproteins and markers of platelet activation (PAI-1) and inflammation (high-sensitivity C-reactive protein, P-selectin) with use of statins and/or fibrates.

Methods:  Evaluation of 174 subjects enrolled in AIDS Clinical Trials Group (ACTG) A5087, a randomized trial of pravastatin (P) or fenofibrate (F) for the treatment of combined hyperlipidemia in persons with HIV. Subjects that failed single-agent therapy at week 12 were given combination (P+F) therapy. Subjects with available specimens were tested for apolipoproteins (Apo) A1 and B, lipoprotein A, adiponectin, PAI-1, P-selectin, HS-CRP at baseline, week 12, and week 48.

Results:  Of the 174 subjects randomized, 102 had available specimens. We selected 74 subjects (37 per randomized arm) randomly for testing and received the following treatment for 48 weeks (based on week-12 response):  F alone (n = 5); P alone (n = 9); F x 12 weeks adding P through week 48 (n = 32); and P x 12 weeks adding F through week 48 (n = 28). Of the total, 71 subjects were male, 54 were white, and 35 (47%) had ≥2 risk factors for coronary heart disease. The subjects were well matched by baseline CD4⁺, HIV viral load, and demographics. There were no significant changes in hs-CRP, PAI-1, and P-selectin from baseline to week 12 or week 12 to 48. From baseline to week 12, adiponectin, ApoB and ApoB/A1 ratios all significantly decreased in the P and F arms. Lp(a) and ApoA1 increased significantly in the F arm only (p = 0.01 for both). From weeks 12 to 48, only ApoB levels (and ApoB/A1 ratios) declined significantly in those treated initially with F and added P (p <0.01 and p = 0.01, respectively). From baseline to week 48, adiponectin levels significantly decreased in the combination treatment groups (p = 0.02 and p <0.01, respectively for those starting with P or F). ApoB decreased significantly in all groups except those treated with F alone.

Conclusions:  Treatment with P or F improves the atherogenic lipid profile within the first 12 weeks of treatment and it is sustained through 48 weeks with combination therapy. Adiponectin levels also decreased with lipid-lowering therapy. General markers of inflammation and platelet activation were not appreciably changed despite improvement in lipids.