In individuals with the HLA-B*57:01 variant allele ("HLA-B*57:01-positive"), abacavir is not recommended and should be considered only under exceptional circumstances.
Please see below for full details of these guidelines, with supporting evidence and disclaimers.
Guidelines regarding the use of pharmacogenomic tests in dosing for abacavir were published in April 2012 in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC) and have been updated in February 2014. CPIC extensively reviewed the literature and concluded no changes were required to the therapeutic recommendations of the abacavir dosing guideline based on HLA-B genotype since the original publication in 2012.
Excerpt from the abacavir dosing guidelines:
We agree with others* that HLA-B*57:01 screening should be performed in all abacavir-naive individuals before initiation of abacavir-containing therapy (see Table 1 below); this is consistent with the recommendations of the FDA, the US Department of Health and Human Services, and the European Medicines Agency. In abacavir-naive individuals who are HLA-B*57:01-positive, abacavir is not recommended and should be considered only under exceptional circumstances when the potential benefit, based on resistance patterns and treatment history, outweighs the risk.
Table 1: Recommended therapeutic use of abacavir based on HLA-B genotype
|Likely phenotype||Genotypes||Examples of diplotypes||Implications for phenotypic measures||Recommendations for abacavir therapy||Classification of recommendation for abacavir therapy a|
|Very low risk of hypersensitivity (constitutes ~94% b of patients)||Absence of *57:01 alleles (reported as "negative" on a genotyping test)||*X/*X c||Low or reduced risk of abacavir hypersensitivity||Use abacavir per standard dosing guidelines||Strong|
|High risk of hypersensitivity (~6% of patients)||Presence of at least one *57:01 allele (reported as "positive" on a genotyping test)||*57:01/*X c *57:01/*57:01||Significantly increased risk of abacavir hypersensitivity||Abacavir is not recommended||Strong|
a Rating scheme described in the supplementary data
b See the supplementary data for estimates of genotype frequencies among different ethnic/geographic groups
c *X = any HLA-B genotype other than *57:01.
HLA-B = human leukocyte antigen B
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