Antiretroviral therapy with HIV protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) has considerably reduced mortality from AIDS. However, lipid abnormalities that may lead to premature atherosclerosis have also become common among patients treated with antiretroviral therapy, and scientists have been seeking the specific mechanisms involved in this relationship. ApoC-III is a newly identified biomarker of lipid metabolism that is believed to be a risk factor for coronary artery disease because it produces elevated levels of triglycerides.
A research team led by Dr. Virgil Brown from the Emory Lipid Research Laboratory and the VA Medical Center working closely with Emory Center for AIDS Research (CFAR) investigators, conducted two research studies -- one in a group of 202 HIV-positive women and one in a group of 271 HIV-positive men at two HIV clinics: the Atlanta VA and the Grady Infectious Diseases Program. In the study of women, two-thirds had received antiretroviral therapy (ARV) for at least three months, 25% had no therapy in the last three months, and 9% had received no ARV therapy. In the study of men, 85% had received ARV for more than three months and 15% had received no ARV therapy.
In both groups, patients treated with either PIs or NNRTIs were more likely to have higher ApoC-III levels than patients on no therapy, and the elevated level of this biomarker corresponded to elevated triglyceride levels in both treatment groups.
"This new ApoC-III biomarker has allowed us to establish a relationship between lipid metabolism and antiretroviral therapy," said Carlos del Rio, MD, associate professor of medicine at Emory University School of Medicine. "This suggests that patients undergoing HIV therapy have impaired metabolism of triclyceride-rich lipoproteins. Because a large number of these patients also smoke and/or have diabetes, they are at increased risk of atherosclerosis, heart attack, and stroke."
The research team consisted of Isabel Hernandez, MD and Erik Folch, MD, postdoctoral fellows in the Emory AIDS International Training and Research Program; Ngoc Anh Le, PhD and Virgil Brown, MD from the Emory Lipid Research Laboratory at the VA Medical Center; Carlos del Rio, MD and Jeffrey Lennox, MD from the Grady Infectious Diseases Program and David Rimland MD Chief of Infectious Diseases at the Atlanta VA Medical Center. The study was funded by the National Institutes of Health.