HLA-B*5701 Testing for Abacavir Hypersensitivity

Introduction to HLA-B*5701 and Abacavir

Patients who carry the HLA-B*5701 allele have approximately a 50% risk of developing a potentially life-threatening hypersensitivity reaction to abacavir, and screening has been proven to eliminate immunologically confirmed hypersensitivity reactions with 100% negative predictive value 1, 2, 3

Abacavir causes an immunologically-mediated hypersensitivity reaction driven by activation of HLA-B*5701, occurring in 3-5% of unscreened patients during the first 6 weeks of treatment 2

The landmark PREDICT-1 trial demonstrated that prospective HLA-B*5701 screening eliminated immunologically confirmed hypersensitivity reactions entirely (0% vs 2.7% in controls, P<0.001) with a negative predictive value of 100% 2

All major HIV treatment guidelines—DHHS, IDSA, IAS-USA, and WHO—recommend HLA-B*5701 testing with the highest evidence rating (strong recommendation, high quality evidence) before initiating abacavir 1, 4, 5, 6, 7
The FDA mandates that HLA-B*5701 testing results should be available if an abacavir-containing regimen is anticipated 4
For HLA-B*5701-positive patients, abacavir-containing regimens are absolutely contraindicated under all circumstances 3

Testing should be performed upon entry into HIV care or before starting therapy with abacavir 8, 1, 5
Results must be documented prominently in the medical record to prevent future inadvertent abacavir exposure 3

This represents one of the most successful applications of pharmacogenetic testing in clinical medicine, with clear actionable results that directly prevent mortality 2
The test has exceptional predictive value: 100% negative predictive value and 47.9% positive predictive value 2

HLA-B*5701 is the only test that must be completed before prescribing a specific antiretroviral agent to prevent immediate life-threatening toxicity 1, 4, 6

Never initiate abacavir-containing regimens for rapid ART start without HLA-B*5701 results available—use integrase inhibitor-based regimens (bictegravir or dolutegravir) with TAF/emtricitabine instead for immediate initiation 4, 3, 9