Interpretive Handbook

Test 60347 :
HLA-B 5701 Genotype, Abacavir Hypersensitivity, Saliva

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

The human leukocyte antigen (HLA) genes help the immune system recognize and respond to foreign substances (such as viruses and bacteria). The HLA-B gene encodes a class 1 HLA molecule in the major histocompatibility complex (MHC), which acts by presenting peptides to immune cells. There are more than 1,500 different HLA-B alleles identified, one of which is the HLA-B*57:01 allele. Frequency of the HLA-B*57:01 allele varies with ethnicity, with a frequency of 6% to 7% in European populations, and up to 20% in Southwest Asian populations.


The HLA-B*57:01 allele has been associated with hypersensitivity to abacavir, a highly effective nucleoside analog reverse-transcriptase inhibitor used to treat HIV infection and AIDS. Per the Clinical Pharmacogenomics Implementation Consortium (CPIC) dosing guidelines for abacavir and HLA-B, individuals who are positive for the HLA-B*57:01 allele are at an increased risk for abacavir hypersensitivity and it is not recommended for use in treating these individuals.


Hypersensitivity reactions, which generally occur during the first 6 weeks of treatment, are often nonspecific and include skin rashes, gastrointestinal symptoms (eg, nausea, vomiting, diarrhea, and abdominal pain), and respiratory symptoms. Fatalities have been reported with abacavir hypersensitivity. Prospective testing for the HLA-B*57:01 genotype and excluding HLA-B*57:01-positive individuals from treatment with abacavir decreases the incidence of abacavir hypersensitivity.


See Abacavir Hypersensitivity Testing and Initial Patient Management Algorithm in Special Instructions.

Useful For Suggests clinical disorders or settings where the test may be helpful

Identifying individuals with an increased risk of hypersensitivity reactions to abacavir, based on the presence of the HLA-B*57:01 allele


Genotyping patients who prefer not to have venipuncture done

Interpretation Provides information to assist in interpretation of the test results

Positivity for human leukocyte antigen allele HLA-B*57:01 confers high risk for hypersensitivity to abacavir.


See Abacavir Hypersensitivity Testing and Initial Patient Management Algorithm in Special Instructions.


For additional information regarding pharmacogenomic genes and their associated drugs, see the Pharmacogenomic Associations Tables in Special Instructions. This resource also includes information regarding enzyme inhibitors and inducers, as well as potential alternate drug choices.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Samples may contain donor DNA if obtained from patients who received heterologous blood transfusions or allogeneic blood or marrow transplantation. Results from samples obtained under these circumstances may not accurately reflect the recipient’s genotype. For individuals who have received blood transfusions, the genotype usually reverts to that of the recipient within 6 weeks. The impact of blood or marrow transplantation on risk of abacavir hypersensitivity reactions is not defined in the literature.


The FDA recommends screening for the HLA-B*57:01 allele before initiating therapy with abacavir. Genotyping is also critical when there is a clinical history of, or when the physician suspects, an abacavir hypersensitivity reaction. However, FDA guidance states that, regardless of HLA-B*57:01 status, abacavir should be permanently discontinued if hypersensitivity cannot be ruled out, even when other diagnoses are possible. Although the negative predictive value of the test is high, a negative HLA-B*5701 result does not preclude the development of a hypersensitivity response to abacavir and cannot substitute for clinical vigilance whenever abacavir therapy is administered. Since symptoms of abacavir hypersensitivity are often nonspecific and can imitate other conditions commonly seen in HIV patients on antiretroviral therapy, the phenotypic diagnosis of abacavir hypersensitivity can be challenging. There is significant variability among patients identified as hypersensitive to abacavir. Not all individuals who are positive for HLA-B*57:01 will have a hypersensitivity reaction.


Rare or novel variants may be present that could lead to false-negative or false-positive results. There may be rare or novel HLA-B alleles that could interfere with this assay. There are, as yet, no data indicating whether any other allele or subtypes are associated with abacavir hypersensitivity.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

An interpretive report will be provided.

Clinical References Provides recommendations for further in-depth reading of a clinical nature

1. Saag M, Balu R, Brachman P, et al: High sensitivity of HLA-B*5701 in whites and blacks in immunologically-confirmed cases of abacavir hypersensitivity. Fourth IAS Conference on HIV Pathogenesis, Treatment, and Prevention. July 22-25, 2007. Sydney. Abstract WEAB305)

2. Martin M, Klein T, Dong B, et al: Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing. Clin Pharmacol Ther 2012:91(4):734-738

3. Martin M, Hoffman J, Freimuth R, et al: Clinical Pharmacogenetics Implementation Consortium Guidelines for HLA-B Genotype and Abacavir Dosing: 2014 update. Clin Pharmacol Ther 2014;95(5):499-500

4. Faruki H, Heine U, Brown T, et al: HLA-B*5701 clinical testing: early experience in the United States. Pharmacogenet Genom 2007;17:857-860

5. Sun HY, Hung CC, Lin PH, et al: Incidence of abacavir hypersensitivity and its relationship with HLA-B*5701 in HIV-infected patients in Taiwan. J. Antimicrob Chemother 2007;60:599-604