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Genetics may predict reaction to HIV drugs


SEATTLE, Feb. 27 (UPI) -- Genetic differences in people infected with HIV might help predict who gets allergic reactions to a commonly used antiviral drug called abacavir, Australian researchers at an AIDS conference said Wednesday.

Abacavir has relatively few side effects compared to similar drugs, however about 5 percent of people taking it in the United States suffer allergic reactions ranging from fever and rash to anaphylactic shock and death.

The researchers used a genetic test to look for specific variants of proteins that make up part of the immune system called the major histocompatibility complex. Every person who tested positive for a particular gene combination developed an allergic reaction to the disease. The test missed only 3 percent of those patients who developed a so-called hypersensitivity reaction, said Simon Mallal of the Centre for Clinical Immunology and Biomedical Statistics at Royal Perth Hospital in Perth.

"This has altered how we treat patients in our practice," he said at the 9th Annual Retrovirus Conference.

Among 200 patients with human immunodeficiency virus treated with abacavir, 13 with a particular constellation of variants called HLA-B*5701, HLA-DR7, and HLA-DQ3 all developed the allergic reaction, Mallal told United Press International. Another five patients developed hypersensitivity reactions to abacavir but did not share this complete sequence of gene variants. About 15 patients developed reactions that might have been due to abacavir but could not be definitely linked to the drug, and so were excluded from analysis. All of the patients who developed allergies to the drug were Caucasian.

Mallal and his colleagues now test HIV patients for the variants before prescribing abacavir. However, he warned that because some people without this particular sequence of gene variants still developed an allergy, the test could not be used to rule out the possibility of an allergic reaction. The study also is reported in the March 2 edition of the medical journal The Lancet.

Other researchers have confirmed Mallal's results. Among HIV-positive patients taking abacavir, 46 percent of the 84 people who developed allergic reactions tested positive for HLA-B57, while just 3.5 percent of those without the allergic reaction had this gene variant. Hypersensitivity to abacavir also was correlated with another gene for an immune signaling molecule that lies nearby on the same chromosome, reported Seth Hetherington of GlaxoSmithKline in Research Triangle Park, N.C.

"This is proof of principle that pharmacogenomics (the idea that genes can predict how patients react to medicine) plays a role in understanding patient responses," Hetherington told UPI.

It is not known whether it is the HLA genes or others lying nearby that cause the allergic reaction, he said at the conference.

The specific set of gene variants identified by Mallal did not accurately identify people with allergic reactions in the U.S. study, suggesting there may be underlying differences between the populations, Mallal said.

"One of the limitations to any therapy is that you're treating a general population with differences in responses," said William Duncan of the National Institute of Allergy and Infectious Diseases in Bethesda, Md. "We're in our infancy in understanding these types of variations ... and we'll see quite a bit more data over the next several years."


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Information in this article was accurate in February 27, 2002. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.