Mallal S, Phillips E, Carosi G, et al. N Engl J Med. 2008;358(6):568–579
PURPOSE OF THE STUDY. Abacavir is associated with severe and potentially life-threatening hypersensitivity reactions in up to 8% of the white population. In 2002, HLA-B*5701 was noted to be highly associated with this hypersensitivity reaction. The purpose of this study was to evaluate the effectiveness of prospective HLA-B*5701 screening to avoid these reactions.
STUDY POPULATION. A total of 1956 HIV-infected patients from 19 countries who had not previously received abacavir were enrolled.
METHODS. Individual patients were randomly assigned to undergo prospective HLA-B*5701 screening, with exclusion of previously known HLA-B*5701 positive patients from abacavir treatment, or to undergo a standard approach of abacavir use without screening. All subjects who started abacavir were observed for 6 weeks, the time frame in which a large majority of hypersensitivity reactions occur. The clinical diagnosis of hypersensitivity reaction to abacavir was assessed further by epicutaneous patch testing.
RESULTS. The prevalence of HLA-B*5701 was 5.76% (109 of 1956 subjects) of the subjects assigned to receive abacavir. Seventy-two percent were men, 84% were white, and 18% had not received antiretroviral therapy previously. Screening effectively eliminated patch-test–confirmed hypersensitivity. None of the subjects in the prospectively screened group had reactions, compared with 2.7% in the control group. This yielded a negative predictive value of 100% and a positive predictive value of 47.9%. Hypersensitivity reactions to antiretroviral therapy were clinically diagnosed in 93 patients, with a significantly lower incidence in the prospectively screened group (3.4%) than in the control group (7.8%) (P < .001).
CONCLUSIONS. HLA-B*5701 screening dramatically reduced the risk of immunologically confirmed hypersensitivity to abacavir. This pharmacogenetic test is useful for reducing the incidence of immunologically mediated hypersensitivity reactions to abacavir.
REVIEWER COMMENTS. This expansive study demonstrated the clinical usefulness of pharmacogenomics testing for immunologically mediated hypersensitivity to a particular drug. This is the first such demonstration for reactions to antiretroviral agents. A major limitation in the use of abacavir has been the concern for a severe hypersensitivity reaction. The availability of this inexpensive test (approximately $80 at our institution) substantially reduces that potential and allows antiretroviral therapy selection to be based on the drug's merit as an effective antiretroviral agent. A unique feature of hypersensitivity to this particular drug is that it is a true T-cell–mediated reaction. Patch testing has been used for many decades to identify offending contact hypersensitivity allergens (eg, nickel). The search for additional biomarkers that would reflect a potential for adverse reactions to other drugs is ongoing. This type of study leads the way in demonstrating clinical effectiveness of such an approach
- Copyright © 2008 by the American Academy of Pediatrics