What is the relationship between Abacavir (Abacavir) and HLA-B*5701 screening in patients considering antiretroviral therapy?

From the Guidelines

HLA-B*5701 screening is essential before prescribing abacavir to patients considering antiretroviral therapy. All patients should undergo this genetic test prior to starting abacavir, as those who carry the HLA-B*5701 allele have a significantly increased risk of developing a potentially life-threatening hypersensitivity reaction to the medication, as supported by the most recent and highest quality study 1. This hypersensitivity reaction typically occurs within the first six weeks of treatment and presents with symptoms such as fever, rash, gastrointestinal issues, and respiratory symptoms. The reaction can be severe and even fatal if abacavir is continued or reintroduced after a reaction has occurred.

Some key points to consider:

• The screening test is highly sensitive and specific, with a negative predictive value approaching 100% 1.
• If a patient tests positive for HLA-B*5701, abacavir should not be prescribed, and alternative antiretroviral medications should be selected.
• This genetic screening represents a successful application of pharmacogenomics in clinical practice, as it effectively prevents a serious adverse drug reaction by identifying susceptible individuals before medication exposure.
• The test needs to be performed only once in a patient's lifetime since genetic status does not change.

It's also worth noting that:

• HLA-B*5701 testing should be performed prior to initiating abacavir therapy to reduce the risk of a hypersensitivity reaction, as recommended by various guidelines 1.
• A negative test result does not rule out the possibility of a hypersensitivity reaction but makes it extremely unlikely, and patients who have negative test results should still be counseled about a hypersensitivity reaction before being treated with abacavir 1.

From the FDA Drug Label

To minimize the risk of a life-threatening hypersensitivity reaction, permanently discontinue EPZICOM if hypersensitivity cannot be ruled out, even when other diagnoses are possible 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 Screening for carriage of the HLA-B5701 allele is recommended prior to initiating treatment with abacavir Screening is also recommended prior to reinitiation of abacavir in patients of unknown HLA-B5701 status who have previously tolerated abacavir For HLA-B*5701-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

The relationship between Abacavir and HLA-B5701 is that patients who carry the *HLA-B5701 allele* are at a high risk for experiencing a hypersensitivity reaction to Abacavir.

• Key points:
  • Screening for the HLA-B*5701 allele is recommended before starting Abacavir treatment.
  • HLA-B*5701-positive patients should not be started on Abacavir unless under close medical supervision and when the potential benefit outweighs the risk.
  • Even in HLA-B*5701-negative patients, Abacavir should be permanently discontinued if a hypersensitivity reaction is suspected.
  • The clinical diagnosis of a hypersensitivity reaction should be the basis of clinical decision-making, regardless of HLA-B*5701 status 2, 2.

From the Research

Abacavir and HLA-B*5701 Relation

The relationship between Abacavir and HLA-B*5701 is significant in the context of antiretroviral therapy. Key points to consider include:

• HLA-B*5701 Screening: Screening for HLA-B*5701 is crucial before initiating Abacavir treatment to prevent hypersensitivity reactions 3, 4, 5, 6, 7.
• Hypersensitivity Reaction: The presence of the HLA-B*5701 allele is strongly associated with an increased risk of hypersensitivity reactions to Abacavir, affecting approximately 5% of treated patients 3, 5, 6.
• Screening Methods: Various methods are available for HLA-B*5701 screening, including genetic assays and flow cytometry, each with its own sensitivity, specificity, and cost-effectiveness 4, 7.
• Effectiveness of Screening: Studies have shown that HLA-B*5701 screening can significantly reduce the risk of hypersensitivity reactions to Abacavir, with a negative predictive value of 100% and a positive predictive value of 47.9% 3.
• Clinical Implementation: Successful implementation of HLA-B*5701 genetic testing services has been reported, allowing for the widespread use of Abacavir while minimizing the risk of hypersensitivity reactions 6.

Key Findings

Some key findings from the studies include:

• A double-blind, prospective, randomized study involving 1956 patients found that HLA-B*5701 screening eliminated immunologically confirmed hypersensitivity reactions to Abacavir 3.
• A comparison of methods for in-house screening of HLA-B*57:01 found that sequence-specific primer PCR with capillary electrophoresis (SSP PCR CE) had the highest sensitivity and specificity 4.
• A meta-analysis of 12 trials found that HLA-B5701 screening reduced the risk of hypersensitivity reactions to Abacavir, with suspected Abacavir hypersensitivity reaction rates of 1.3% or less in HLA-B5701-negative patients 5.
• A national HLA-B*5701 genetic testing service in Canada has been successfully implemented, with over 11,000 tests performed and a positive rate of 6.3% 6.
• A rapid flow cytometry method for HLA-B57 phenotyping has been developed as a sensitive and rapid alternative to HLA typing for genetic screening of Abacavir hypersensitivity syndrome 7.