Pharmacogenomic Test Can Prevent Reactions to HIV Drug
In subjects screened for allele before treatment, none have confirmed abacavir reaction
WEDNESDAY, Feb. 6 (HealthDay News) -- Testing people with HIV-1 infection for the HLA-B*5701 allele before administering abacavir can identify those at high risk for hypersensitivity reactions to the drug, according to research published in the Feb. 7 issue of the New England Journal of Medicine.
Simon Mallal, of Murdoch University in Perth, Australia, and colleagues randomized 1,956 patients (72 percent men, 84 percent white) into two groups. One group was prospectively tested for HLA-B*5701 before abacavir treatment, with those testing positive excluded from treatment. The other group was treated, then tested retrospectively. Patients with hypersensitivity reactions were diagnosed, and later had epicutaneous patch testing for confirmation.
HLA-B*5701 prevalence was 5.6 percent. No patient in the prospective screening group had a confirmed hypersensitivity reaction, versus 2.7 percent in the control group. Screening offered a negative predictive value of 100 percent and a positive predictive value of 47.9 percent. Clinical diagnoses of hypersensitivity -- which are subject to false-positives -- were lower in the prospective screening group than the control group (3.4 percent versus 7.8 percent).
"Is it appropriate to use HLA-B*5701 as a genetic biomarker in routine clinical practice? The answer, in my opinion, is yes," writes Magnus Ingelman-Sundberg, Ph.D., of the Karolinska Institute in Stockholm, Sweden. "HLA-B*5701 genotyping appears to be an effective pharmacogenomic test in white populations, with high sensitivity and modest specificity, allowing clinicians to avert a specific toxic effect of a drug. It is also an important precedent for further pharmacogenomic research toward safer, more effective individualized drug therapy."
Several of the study authors report financial relationships with GlaxoSmithKline, and Mallal is sole shareholder of a company with a patent pending for HLA-B*5701 testing. Ingelman-Sundberg has received grant support from AstraZeneca.