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

Abstract

Context: HIV 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).

Objective: The aim was to test a targeted, comprehensive, additive approach to treating the dyslipidemia.

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

Participants: Hypertriglyceridemic 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).

Interventions: Subjects 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 measures: We 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).

Results: Fenofibrate 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.

Conclusions: A 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.

Trial registration: ClinicalTrials.gov NCT00246376.

Fig. 1.

Flow diagram of subject screening, recruitment, and randomization. At randomization, subjects were stratified by three combinations of ART classes: protease inhibitor-containing regime (PI), nonnucleoside reverse transcriptase inhibitor-containing regime (NNRTI), and regime with three nucleoside reverse transcriptase inhibitors without PI or NNRTI (NRTI-only).

Fig. 2.

Lipid changes within individual subjects, displayed by group. All 191 subjects included in the analysis are represented, and “post” refers to the last value measured in each subject. The slope (m) represents the magnitude of the mean group change (in milligrams per deciliter), and r² represents the correlation of the change with the treatment. The slope and correlation coefficients were calculated by linear regression analysis using SigmaPlot (Systat Software, Inc., San Jose, CA). TG, Triglyceride; UC, usual care; F, fenofibrate; N, niacin.