Race/Ethnicity Is Predictor for Some HIV-1 Therapy

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Researchers from the University of Massachusetts Amherst and the University of Pennsylvania have shown that race/ethnicity is a predictor of plasma lipids in patients with HIV-1 on HAART (highly active antiretroviral therapy). The researchers, led by Andrea Foulkes, assistant professor of biostatistics at UMass Amherst, and Muredach Reilly, assistant professor of medicine at Penn, examined the influence of racial/ethnic influences on plasma lipoproteins, and the genetic effects on lipids in patients with HIV-1.

“One of the most important findings of this research is the need to consider the role of ethnicity when looking at the potential complications of HAART,” Foulkes says. “This is of particular importance given the global spread of HIV and the large-scale initiatives to increase access to therapies. Ultimately, this will allow clinicians to identify improved treatment strategies and provide the best care to their patients.”

The study, published in the January issue of PloS, Medicine, focuses on the abnormally high levels of triglycerides and low levels of HDL, the “good” cholesterol, found in the blood of HIV-1 infected patients on protease inhibitors as part of combination antiretroviral therapy. 

These blood fats, known as lipids, put people in the general population at risk for heart attack and stroke. In their study of 626 patients with HIV-1 on antiretroviral therapy, the researchers found that the lipid abnormalities stemming from protease inhibitors varied by race/ethnicity and were associated with variant forms of apoC-III.

The researchers cautioned that much larger, controlled studies would be needed before findings from this initial study could be used by physicians to help tailor antiretroviral regimens to individuals’ genetic profiles. They also emphasized that genetics is likely just one factor involved in the race-related differences seen in the lipid levels. Diet, exercise and other environmental factors, they noted, probably play a role as well.

HIV-1 infection has become a chronic, manageable condition for patients who have long-term access to highly active antiretroviral therapy. However, in some patients, highly active antiretroviral therapy causes various metabolic complications, including the development of dyslipidemia. Some protease inhibitors, a class of anti-HIV drugs, have been associated with elevated levels of cholesterol, triglyceride, and low high-density lipoprotein cholesterol. Protease-based highly active antiretroviral therapy has also been associated with increased risk for cardiovascular disease, which could, it has been suggested, lead to a future epidemic of cardiovascular disease in patients with HIV-1 treated with this regimen long term.

These findings are believed to be the first evidence for race/ethnicity–specific differences in both the occurrence of dyslipidemia on antiretroviral therapy (ART) and the influence of genetic factors on the occurrence of protease inhibitor-related lipid abnormalities. But the authors stress that the findings do not imply that “race” per se is responsible for functional differences between gene variants. Rather, it is more likely that differences relate to either variation in the inheritance pattern of haplotye blocks of the lipoprotein apoC-III gene, which the authors found to vary with race/ethnicity, or to the confounding influences of additional environmental and/or genetic factors.

The authors also point out that strategies that identify individuals with HIV-1 at increased risk of antiretroviral therapy-related metabolic complications will improve the selection of appropriate antiretroviral regimens and preventive cardiovascular therapies, and ultimately may decrease the long-term cardiovascular risk of these patients.

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