NEW ORLEANS – Daily supplementation with high-dose omega-3 fatty acids significantly slashed levels of triglycerides and C-reactive protein (CRP) among people with HIV infection at 2 years, according to a randomized study.
“This is the longest randomized, controlled trial to date of high-dose omega-3 in the HIV infected to evaluate long-term effects on lipids, inflammation, and vascular function,” Gretchen Volpe, MD, said at an annual scientific meeting on infectious diseases. Prior studies were limited to 24 weeks or fewer of omega-3 supplementation, she added.
The trial is part of a bigger trend, one where investigators strive to improve duration and quality of life for people living with HIV/AIDS because of the field’s success in managing HIV infection itself.
“Cardiovascular disease is prevalent in persons with HIV,” said Dr. Volpe of Tufts Medical Center in Boston. “HIV increases cardiovascular disease through several pathways – including dyslipidemia, chronic inflammation, and vascular dysfunction.” Both HIV infection itself as well as antiretroviral therapy can have atherogenic effects on vasculature, she added.
Omega-3 fatty acids have been shown to reduce triglycerides in HIV-infected and non–HIV infected people, and they may reduce inflammation by decreasing the inflammatory mediator arachidonic acid, Dr. Volpe said.
She and her colleagues enrolled HIV-infected adults on stable antiretroviral therapy with fasting triglycerides between 150 mg/dL and 2,500 mg/dL at baseline. They randomized 43 people to 4 g omega-3 (Lovaza) daily, and another 40 people to placebo in an intent-to-treat analysis.
The mean age was 51 years, 21% were women, and there were no significant differences between groups at baseline on lipid parameters or statin use. Most patients (95%) were virologically suppressed, with a mean CD4+ count of 648 cells/mcL. The mean duration of HIV infection was 16 years.
The median decrease in triglycerides at 24 months was 68 mg/dL in the omega-3 group, compared with 22 mg/dL in the placebo group, a significant difference (P = .041). Another primary outcome, change in C-reactive protein as an indication of systemic inflammation, decreased 0.3 mg/L in treated participants, versus an increase of 0.6 mg/L in the placebo group. That difference also was statistically significant (P = .008).
In contrast, there were no significant differences in HDL-C changes, arterial stiffness, or brachial artery reactivity between groups at 2 years. Serious adverse event rates did not differ, either, Dr. Volpe reported at the combined annual meetings of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, and the Pediatric Infectious Diseases Society
“Adherence even over a 2-year trial is feasible, and efficacy may increase over time – we noted our 24-month data were more statistically significant than our 12-month data,” Dr. Volpe observed. Omega-3 fatty acid supplementation is well tolerated with limited side effects, she added. “Omega-3 fatty acid supplementation [also] may reduce inflammation as measured by CRP, even for those whose CRP was in the normal range at baseline.”
Total cholesterol did not significantly differ between groups at any time point, Dr. Volpe noted. “But we noticed a trend toward greater reduction in total cholesterol in the treatment group at 12 months and 24 months. There we no differences at any time point between groups in LDL cholesterol, which allays some concerns that fatty acids might increase LDL.”
The use of the prescription formulation of omega-3 fatty acids could be a limitation of the study, Dr. Volpe said, because not all people at risk may be able to access or afford it.
During a question session after the presentation, a meeting attendee asked about over-the-counter formulations that she could recommend to her patients. “We used the high dose, because some previous studies showed a dose-dependent response,” Dr. Volpe responded. “This was a purified formulation, so we could know what we were giving. ... I don’t know how to solve that problem in real life, but maybe use the best preparation that you are most familiar with.”
Another attendee asked about any differences between groups in statin use, alcohol consumption, or smoking. “We had about 30% statin users in either arm,” Dr. Volpe replied. “Some studies have shown that statins reduce or eliminate the effects of omega-3s, whereas other studies have shown that high-dose, high-efficacy statins improve the effects of omega-3s. Whatever the effect was, it was well distributed between groups.” Smoking and drinking rates did not significantly different between groups, she noted.
In a video interview at the meeting, Dr. Volpe discussed the study and its findings.
Dr. Volpe had no relevant disclosures.