Background.Omega‐3 fatty acids (fish oils) reduce fasting serum triglyceride levels and cardiovascular disease risk in individuals without HIV infection. Whether omega‐3 fatty acid supplementation can reduce hypertriglyceridemia associated with antiretroviral therapy is not known.

Methods.We conducted an open‐label, randomized trial that enrolled 52 patients receiving 3 active antiretrovirals who had fasting triglyceride levels of >200 mg/dL and were randomized to receive nutritionist‐administered dietary and exercise counseling with or without fish oil supplementation for 16 weeks.

Results.Patients assigned to receive fish oil experienced a 25% mean decline in fasting triglyceride levels at week 4 (95% CI, −34.6% to −15.7% change), compared with a 2.8% mean increase among patients assigned to receive counseling alone (95% CI, −17.5% to +23.1% change) ( ). By week 16, the mean reduction in triglyceride levels in the fish oil arm remained significant, at 19.5% (95% CI, −34.9% to −4.0% change), whereas the mean decrease in the diet and exercise only arm was 5.7% (95% CI, −24.6% to +13.2% change); however, the difference between study arms was no longer statistically significant ( ). Low‐density lipoprotein cholesterol levels had increased by 15.6% (95% CI, +4.8% to +26.4% change) at week 4 and by 22.4% (95% CI, +7.91% to +36.8% change) at week 16 in the fish oil arm but did not change in the diet and exercise only group. Fish oil was well tolerated; only 1 patient experienced treatment‐limiting toxicity.

Patients assigned to receive fish oil experienced a 25% mean decline in fasting triglyceride levels at week 4 (95% CI, −34.6% to −15.7% change), compared with a 2.8% mean increase in patients assigned to receive counseling alone (95% CI, −17.5% to 23.1% change) ( ). By week 16, the mean reduction in triglyceride levels in the fish oil arm remained significant, at 19.5% (95% CI, −34.9% to −4.0% change), whereas the mean decrease in the diet and exercise only arm was 5.7% (95% CI, −24.6% to 13.2% change); however, the difference between study arms was no longer statistically significant ( ). Low‐density lipoprotein cholesterol levels had increased by 15.6% (95% CI, 4.8%–26.4% change) at week 4 and by 22.4% (95% CI, 7.91%–36.8% change) at week 16 in the fish oil arm but did not change in the diet and exercise only group. Fish oil was well tolerated; only 1 patient experienced treatment‐limiting toxicity.

Conclusions.Supplementation with omega‐3 fatty acids in combination with dietary and exercise counseling was well tolerated and reduced fasting triglyceride levels in patients receiving antiretrovirals. To what extent the increase in low‐density lipoprotein cholesterol levels observed in patients assigned this intervention is attributable to omega‐3 fatty acid supplementation and whether this increase attenuates any benefit in lowering triglyceride levels is unclear. Given these results, further investigation of omega‐3 fatty acid supplementation for the treatment of hypertriglyceridemia in HIV‐infected patients is warranted.