Ethnic differences in response to HIV medicines

Researchers from the University of Massachusetts 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 and Muredach Reilly, examined the influence of racial/ethnic influences on plasma lipoproteins, and the genetic effects on lipids in patients with HIV-1.

In a cross-sectional analysis of 626 patients participating in several ongoing AIDS Clinical Trial Group studies, Foulkes and colleagues looked at the way that race/ethnicity, genetic variants of lipoproteins apoC-III/apoA-I, and protease inhibitors (a class of drugs used against HIV) affected plasma lipids. Overall, Black patients on HAART had a lipid profile that meant they were likely to be less prone to atheroma than White and Hispanic patients. They also found that in Hispanic, but not in White or Black patients, certain genetic variants of apoC-III were associated with less dyslipidemia in patients exposed to protease inhibitor-containing highly active antiretroviral therapy.

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 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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Citation: Foulkes AS, Wohl DA, Frank I, Puleo E, Restine S, et al. (2006) Associations among race/ethnicity, apoC-III genotypes, and lipids in HIV-1-infected individuals on antiretroviral therapy. PLoS Med 3(3): e52.

CONTACTS:
Andrea S. Foulkes
School of Public Health and Health Sciences
University of Massachusetts
404 Arnold House
715 North Pleasant Street
Amherst, MA USA 01003
413-545-1881
413-545-1645 fax
foulkes@schoolph.umass.edu

Muredach Reilly
University of Pennsylvania
School of Medicine
909 BRB2/3, 415 Curie Blvd.
Philadelphia, PA USA 19104
215-573-1214
215-573-2094 (fax)
muredach@spirit.gcrc.upenn.edu

Related PLoS Medicine Perspective article:
Citation: Mallon PWG (2006) Antiretroviral therapy and dyslipidaemia: Unlocking the code. PLoS Med 3(3): e85.

PLEASE ADD THE LINK TO THE PUBLISHED ARTICLE IN ONLINE VERSIONS OF YOUR REPORT: http://dx.doi.org/10.1371/journal.pmed.0030085

PRESS-ONLY PREVIEW OF THE PERSPECTIVE: http://www.plos.org/press/plme-03-03-mallon.pdf

CONTACT:
Patrick W.G Mallon
HIV Clinical Trial Unit
St Vincent's Hospital
Sydney
Australia
61-29-295-8419
p.mallon@cfi.unsw.edu.au

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