Objective: To demonstrate relationships between plasma high-density lipoprotein (HDL) cholesterol and fat expansions in the fat redistribution syndrome. Design: Patients who had significant buffalo humps or intra-abdominal fat (IAF) expansions were identified and their HDL levels were measured. Control patients were all those undergoing a single trial of antiretroviral treatment. Some patients answered a self-administered questionnaire concerning self-perceived fat expansions, and their responses were related to their HDL levels. In other patients, relationships were studied between IAF measured by cross-section computerized tomography scans and HDL levels. Finally, patients who had IAF > 70 cm(2), were administered niacin, 3000 mg/day for greater than or equal to 6 months, in order to test whether raising HDL induced a decrease in IAF. Results: Twenty-three patients with buffalo humps had mean HDL of 30.4 mg/dl; 47 HIV-positive controls had mean HDL of 41.9 mg/dl (P=0.001). In 27 patients, IAF area and HDL were negatively correlated (r, 0.40; P=0.04). Among these 27, the 17 patients with IAF area > 100 cm(2) had mean HDL of 35.3 mg/dl; the 10 patients with IAF area < 100 cm(2) had mean HDL of 51 mg/dl (P<0.05). The 2 4 patients who indicated in a questionnaire that they had self-perceived IAF expansion had a median HDL of 36.0 mg/dl; the 20 who indicated that they did not have IAF expansion had a median HDL of 44.5 mg/dl (P=0.06). IAF decreased by 26.9% in 13 (81%) of the 16 patients who took niacin for 1 year; and the decrease in IAF was associated with a significant (P=0.002) increase in HDL. (C) 2002 Lippincott Williams Wilkins.