What are the implications of being HLA-B*57:01 (Human Leukocyte Antigen B 57:01) positive?

From the Guidelines

If you are HLA-B*57:01 positive, you should be concerned about a potentially severe hypersensitivity reaction to abacavir, an antiretroviral medication used to treat HIV, and abacavir should be avoided completely. This genetic variant significantly increases your risk of developing abacavir hypersensitivity syndrome, which can be life-threatening 1. The hypersensitivity reaction typically occurs within the first six weeks of treatment and presents with symptoms like fever, rash, gastrointestinal issues, and respiratory symptoms.

Key Considerations

• The reaction occurs because the HLA-B*57:01 variant causes your immune system to recognize abacavir as a foreign threat, triggering an excessive immune response 1.
• This genetic test is now standard practice before prescribing abacavir, as identifying this variant beforehand prevents these dangerous reactions 1.
• If you've tested positive, make sure all your healthcare providers are aware of this result, and ensure it's prominently noted in your medical records to prevent accidental prescription of abacavir in the future.

Clinical Implications

• Abacavir hypersensitivity reactions related to HLA-B*57:01 occur in 3 to 5% of patients during the first 6 weeks of treatment 1.
• Testing for the HLA-B*57:01 allele is now recommended by the FDA before initiating antiviral treatment that includes abacavir based on results of PREDICT-1 (Prospective Randomized Evaluation of DNA Screening in a Clinical Trial) 1.
• Alternative HIV medications should be used instead of abacavir in HLA-B*57:01 positive individuals to prevent hypersensitivity reactions.

From the FDA Drug Label

When therapy with EPZICOM has been discontinued for reasons other than symptoms of a hypersensitivity reaction, and if reinitiation of EPZICOM or any other abacavir-containing product is under consideration, carefully evaluate the reason for discontinuation of EPZICOM to ensure that the patient did not have symptoms of a hypersensitivity reaction If the patient is of unknown HLA-B5701 status, screening for the allele is recommended prior to reinitiation of EPZICOM. Risk Factor: HLA-B5701 Allele: Studies have shown that carriage of the HLA-B5701 allele is associated with a significantly increased risk of a hypersensitivity reaction to abacavir For HLA-B5701-positive patients, initiating or reinitiating treatment with an abacavir-containing regimen is not recommended and should be considered only with close medical supervision and under exceptional circumstances where potential benefit outweighs the risk.

Hypersensitivity Reaction is the main concern for HLA-B*5701 positive patients.

• Abacavir should not be initiated or reinitiated in HLA-B*5701 positive patients unless under exceptional circumstances with close medical supervision.
• The patient is at a significantly increased risk of a hypersensitivity reaction to abacavir.
• Close medical supervision is required if abacavir is considered for HLA-B*5701 positive patients 2

From the Research

HLA-B 57:1 Positive: Key Considerations

• Being HLA-B 57:1 positive increases the risk of abacavir hypersensitivity reaction, as shown in studies 3, 4, 5.
• The HLA-B57:01 allele is strongly associated with hypersensitivity reactions to abacavir, with a significant reduction in hypersensitivity reactions when HLA-B57:01 screening is implemented 4, 5.
• Clinical vigilance is essential in managing individuals starting abacavir, regardless of HLA-B57:01 status, as not all abacavir-related side effects occur as a result of classic HLA-B57:01-mediated hypersensitivity reaction 3.

Abacavir Hypersensitivity Reaction

• The incidence of hypersensitivity reactions to abacavir decreases significantly with HLA-B*57:01 screening, from 1.3% in the pre-screening period to 0.2% in the post-screening period 5.
• HLA-B*57:01 screening has been shown to be cost-effective in preventing hypersensitivity reactions, with a cost per hypersensitivity reaction avoided of €306 6.
• The cost-effectiveness of HLA-B*57:01 testing is influenced by factors such as allele prevalence, pharmacological therapy costs, and the cost of the test itself 7, 6.

Clinical Implications

• Patients who are HLA-B*57:01 positive should not be treated with abacavir, as the risk of hypersensitivity reaction is significantly increased 3, 4.
• HLA-B*57:01 screening should be performed before initiating abacavir treatment to minimize the risk of hypersensitivity reactions 4, 5.
• Clinical diagnosis of suspected abacavir hypersensitivity reaction in allele non-carriers remains crucial for further clinical decision making 3.