In addition to elevated cholesterol, HIV-infected persons may have elevated levels of triglycerides, which have been associated with increased likelihood of pancreatitis and cardiovascular risks in uninfected persons. Hypertriglyceridemia has been associated with HIV-associated catabolism in patients with the wasting syndrome, has also been documented in patients who are asymptomatic, including those not taking PIs. However, the addition of PIs may be associated with significant increase in blood triglycerides, occasionally leading to acute complications, like pancreatitis. Gemfibrozil inhibits peripheral lipolysis, decreases hepatic extraction of blood lipids, resulting in increases in blood HDL (associated with good cardiovascular risk status) and decreases in blood LDL (which carries cholesterol throughout the body), and alters the transport of VLDL, which carries triglycerides in the blood. The net effect is a decrease in blood triglycerides in uninfected persons with familial or acquired abnormalities. Hewitt and colleagues studied 9 patients with very high triglyceride levels on PIs (716 to 2,847 mg/dl, normal being less than 150). Virtually all of them had a decrease in their triglyceride levels on 600 mg of gemfibrozil twice a day, however, the majority had high cholesterols which did not appreciably decline. In 3 patients who subsequently changed PIs (from indinavir to nelfinavir), triglyceride levels rose again, and rebounding was seen when patients discontinued gemfibrozil use. No adverse reactions were reported. In patients with hypertriglyceridemia on PIs, gemfibrozil seems to be safe and well-tolerated, but larger studies are needed to assess long term efficacy in chronic and changing regimens and other treatments will be needed to treat the common occurance of elevated cholesterol in persons living with HIV.