PURPOSE: Patients with dyslipidemia associated with HIV-1 infection and highly active antiretroviral therapy (HAART) have elevated levels of Lp-PLA2 and CCL5/regulated on activation, normal T-cell expressed and secreted (RANTES), which may increase the risk of cardiovascular disease. PURPOSE: This study aimed to determine whether an intensive diet and exercise (D/E) program, independently or combined with fenofibrate or niacin, could reduce Lp-PLA2 or RANTES. METHODS: Patients with hypertriglyceridemic HIV on stable HAART (n = 107) were randomized to one of five interventions: (1) usual care, (2) D/E with placebos, (3) D/E with fenofibrate and placebo, (4) D/E with niacin and placebo, or (5) D/E with fenofibrate and niacin for 24 wk. Lp-PLA2 and RANTES concentrations were measured in fasting plasma samples at baseline and postintervention. General linear models were used to compare Lp-PLA2 and RANTES levels between the five groups postintervention, controlling for baseline levels, age, body mass index, CD4 T-cell count, viral load, duration of infection, and HAART. RESULTS: At baseline, fasting plasma Lp-PLA2 (388.5 +/- 127.5 ng/mL) and RANTES (43.8 +/- 25.5 ng/mL) levels were elevated when compared with healthy controls. Posttreatment Lp-PLA2 mass was lower in patients who received D/E only (323.0 +/- 27.2 ng/mL), D/E plus fenofibrate (327.2 +/- 25.9 ng/mL), and D/E plus niacin (311.1 +/- 27.8 ng/mL) when compared with patients receiving usual care (402.2 +/- 25.3 ng/mL). RANTES concentrations were not significantly affected by any intervention. CONCLUSIONS: Elevated plasma Lp-PLA2 mass can be reduced by an intensive D/E program in patients with HIV/HAART-associated dyslipidemia. RANTES is elevated but is not reduced by lifestyle modification, fenofibrate, or niacin.

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