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