Combination of niacin and fenofibrate with lifestyle changes improves dyslipidemia and hypoadiponectinemia in HIV patients on antiretroviral therapy: results of "heart positive," a randomized, controlled trial.

contextHIV patients on antiretroviral therapy (ART) have a unique dyslipidemia [elevated triglycerides and non-high-density lipoprotein-cholesterol (HDL-C), low HDL-C] with insulin resistance (characterized by hypoadiponectinemia).

objectiveThe aim was to test a targeted, comprehensive, additive approach to treating the dyslipidemia. DESIGN AND

settingWe conducted a randomized, double-blind, placebo-controlled, 24-wk trial of lifestyle modification, fenofibrate, and niacin in multiethnic HIV clinics at an academic center.

participantsHypertriglyceridemic adult patients were stratified on three combinations of ART classes. Subjects retained at the first measurement (2 wk) after entry were included in the analysis (n = 191).

interventionsSubjects were randomized into five treatment groups: usual care (group 1); low-saturated-fat diet and exercise (D/E; group 2); D/E + fenofibrate (group 3); D/E + niacin (group 4); or D/E + fenofibrate + niacin (group 5).

main outcome measuresWe measured changes in fasting triglycerides, HDL-C, and non-HDL-C (primary), and in insulin sensitivity, glycemia, adiponectin, C-reactive protein, energy expenditure, and body composition (secondary). Data were analyzed as a factorial set of treatment combinations using a mixed repeated measures model, last observation carried forward, and complete case approaches (groups 2-5), and as an unstructured set of treatments (groups 1-5).

resultsFenofibrate improved triglycerides (P = 0.002), total cholesterol (P = 0.02), and non-HDL-C (P = 0.003), whereas niacin improved HDL-C (P = 0.03), and both drugs decreased the total cholesterol-to-HDL-C ratio (P = 0.005-0.01). The combination of D/E, fenofibrate, and niacin provided maximal benefit, markedly reducing triglycerides (-52% compared to usual care; P = 0.003), increasing HDL-C (+12%; P < 0.001), and decreasing non-HDL-C (-18.5%; P = 0.003) and total cholesterol-to-HDL-C ratio (-24.5%; P < 0.001). Niacin doubled adiponectin levels.

conclusionsA combination of fenofibrate and niacin with low-saturated-fat D/E is effective and safe in increasing HDL-C, decreasing non-HDL-C and hypertriglyceridemia, and ameliorating hypoadiponectinemia in patients with HIV/ART-associated dyslipidemia.