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Preventing Abacavir Hypersensitivity Reaction

Screening prospectively for HLA-B*5701 — and avoiding abacavir use in those who test positive — reduces the incidence of hypersensitivity reaction to this NRTI.

Abacavir is an attractive drug for treating HIV-infected patients because it is less likely than older nucleoside reverse-transcriptase inhibitors to cause lipodystrophy and other metabolic complications. However, 5% to 8% of patients who take this agent develop a hypersensitivity reaction (HSR) that can be life-threatening if abacavir is continued or if the person is rechallenged with the drug. Previous studies have shown that abacavir HSR is associated with the HLA-B*5701 allele. Now, in a manufacturer-supported trial involving 1956 HIV-infected adults in 19 countries, investigators have examined whether the incidence of abacavir HSR can be reduced by screening for HLA-B*5701 and avoiding the drug in those who test positive.

Participants were randomized to receive abacavir without prospective HLA-B*5701 screening (control group) or to have HLA-B*5701 testing and receive abacavir only if negative for this marker (prospective-screening group). Abacavir HSR was diagnosed by clinical criteria (clinically diagnosed HSR) and confirmed by skin-patch testing (immunologically confirmed HSR). The prevalence of HLA-B*5701 in this predominantly white study population was 5.6%.

The incidence of immunologically confirmed HSR was 0% in the prospective-screening group compared with 2.7% in the control group, yielding a negative predictive value of 100% and a positive predictive value of 47.9% for the test. The incidence of clinically diagnosed HSR was also lower in the prospective-screening group than in the control group (3.4% vs. 7.8%; P<0.001). Of note, no cases of clinically diagnosed HSR in HLA-B*5701–negative patients were immunologically confirmed, suggesting that another agent might be causing the reactions in such individuals. Most cases of HSR occurred 2 weeks after abacavir initiation.

Comment: Predicting the risk for abacavir HSR with HLA-B*5701 screening is the first demonstration of the utility of pharmacogenetic testing in HIV-infected patients. Although the population in this study was mostly white, other studies have shown comparable sensitivity of the test for immunologically confirmed HSR in both white and black populations (abstract WEAB305, 4th IAS Conference on HIV Pathogenesis, Treatment and Prevention, 2007). The latest Department of Health and Human Services HIV treatment guidelines recommend HLA-B*5701 testing before initiating abacavir; patients found to be HLA-B*5701–positive should not be prescribed abacavir. There has been much talk in recent years about personalized medicine; the use of genetic screening to improve drug safety is a perfect example of what the future holds.

— Rajesh T. Gandhi, MD

Published in Journal Watch Infectious Diseases February 6, 2008

Citation(s):

Mallal S et al. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med 2008 Feb 7; 358:568.

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• Medline abstract (Free)

Ingelman-Sundberg M. Pharmacogenomic biomarkers for prediction of severe adverse drug reactions. N Engl J Med 2008 Feb 7; 358:637.

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• Medline abstract (Free)