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Genetic basis identified for abacavir hypersensitivity in HIV patients
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NEW YORK (Reuters Health) - A significant proportion of patients with HIV infection who are treated with the nucleoside reverse-transcriptase inhibitor abacavir (Ziagen) develop a potentially fatal hypersensitivity reaction to the drug. Now, researchers have identified a genetic mutation that predisposes to abacavir hypersensitivity.
In the March 23 issue (early online edition, March 15) of the Proceedings of the National Academy of Sciences, Dr. Simon Mallal of the Royal Perth Hospital, Australia, reports with colleagues there and elsewhere on the results of recombinant genetic mapping performed in 248 consecutive participants in the Western Australia HIV Cohort Study. Eighteen of the subjects developed hypersensitivity to abacavir.
According to the article, symptoms of abacavir hypersensitivity "usually appear within the first 6 weeks of treatment...and include fever, rash, gastrointestinal symptoms...and lethargy or malaise."
The researchers had previously shown that the presence of HLA-B*5701 was a strong predictor of abacavir hypersensitivity. Now, they discovered that a combination of HLA-B*5701 and a haplotypic polymorphism of Hsp70-Hom was present in 17 of the 18 hypersensitive patients.
In contrast, this genetic combination was present in only 1 of the 230 patients who tolerated abacavir with no complications.
"From a clinical perspective, these data indicate that the prospective use of a genetic test...would reduce the prevalence of definite abacavir hypersensitivity in our cohort from 8% to 0.4%," the investigators point out.
They conclude, "These findings have significant implications both in terms of the clinical management of abacavir-exposed HIV-infected patients and the elucidation of basic pathophysiological mechanisms underlying this and other idiosyncratic drug hypersensitivity reactions."
Proc Natl Acad Sci USA 2004;101:4180-4185
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