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Home > Treatment > HIV Meds Quarterly > Spring 2008 > HLA-B*5701 and Abacavir HSR
HLA-B*5701 Screening for Abacavir Hypersensitivity
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The reported rate of hypersensitivity reaction (HSR) to abacavir is approximately 5-8% among whites of European ancestry and 2-3% among African Americans. Abacavir HSR has been strongly associated with the major histocompatability complex class 1 allele HLA-B*5701. The prevalence of this allele varies across populations. A recent study provides strong evidence that pretreatment screening for HLA-B*5701 and avoidance of abacavir in patients with the allele significantly decreases risk of abacavir HSR.

PREDICT-1, a double-blind study, randomized more than 1,900 HIV-infected patients to immediate treatment with abacavir (control group) vs prospective HLA-B*5701 testing and withholding of abacavir from those with HLA-B*5701. All patients who developed clinically suspected HSR, and a group of 100 patients without HSR, were subsequently screened for true (immunologically confirmed) abacavir hypersensitivity by skin patch testing.

Results from this study of primarily white subjects showed an overall HLA-B*5701 prevalence of 5.6%. No cases of HSR occurred in patients who screened negative for HLA-B*5701 (negative predictive value = 100%), whereas immunologically confirmed HSR occurred in 2.7% of controls (p < .001). Importantly, because abacavir HSR is a clinical diagnosis, the proportion of false-positive (suspected) HSR cases also was significantly lower in the screened group (3.4%) than in the control group (7.8%; p < .001).

This study demonstrates that HLA-B*5701 testing identifies persons at high risk of abacavir HSR. The results of this study require confirmation in nonwhite populations, but it appears that screening for HLA-B*5701 and avoiding abacavir in patients with the HLA-B*5701 allele substantially decreases (or perhaps eliminates) the risk of true abacavir HSR, which can be serious, and it also decreases the likelihood of mistaken diagnosis of HSR, which leads to unnecessary (and permanent) discontinuation of abacavir. Note that HLA-B*5701 testing is not a substitute for proper patient counseling and astute clinical judgement.

The U.S. Department of Health and Human Services' Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents now recommend screening for HLA-B*5701 before initiating treatment with abacavir. For patients who test negative for HLA-B*5701, the guidelines categorize abacavir + lamivudine as a "preferred" nucleoside backbone for use in initial antiretroviral therapy.

References

  1. Mallal S, Phillips E, Carosi G, et al; PREDICT-1 Study Team. HLA-B*5701 screening for hypersensitivity to abacavir. N Engl J Med. 2008 Feb 7;358(6):568-79. Available at http://www.ncbi.nlm.nih.gov/pubmed/18256392. Accessed April 7, 2008.
  2. Panel on Antiretroviral Guidelines for Adult and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. January 29, 2008; 1-128. Available at http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf. Accessed April 7, 2008.
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