Interpretive Handbook

Test 89346 :
HLA-B 5701 Genotype, Abacavir Hypersensitivity, Blood

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

Human leukocyte antigen (HLA) genes are localized to chromosome 6. These genes affect the response of the immune system to infection by viruses and bacteria, and direct antibody production against foreign substances or antigens. HLA-B is a subclass of the HLA system. Based on DNA sequence variation, over 2,400 different versions of the gene, that codes for the HLA-B antigen, have been identified in the human population. The HLA-B*57 family consists of at least 57 closely related genes. Around 5% to 8% of the Western European and Hispanic populations express 57-like antigens, so this represents a common HLA genotype. This genotype is less frequent in other ethnic groups, and is found in <2% of people of African origin.


The products of the 5701 gene family members have been associated with hypersensitivity to abacavir, a highly effective nucleoside analog reverse-transcriptase inhibitor used to treat HIV infection and AIDS. The HLA-B*5701 genotype has been shown to be highly predictive of abacavir hypersensitivity in Western European populations. 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. Prospectively testing for the HLA-B*5701 genotype and excluding HLA-B*5701-positive individuals from treatment with abacavir decreases the incidence of abacavir hypersensitivity.


The HLA-B*5701 allele is also associated with flucloxacillin-induced liver injury in a single study. Individuals who have at least 1 copy of the HLA-B*5701 allele have an 80-fold increased risk of serious liver injury when treated with flucloxacillin. The actual liver injury is thought to be caused by a polymorphism in the neighboring HCP5 gene that is located in the major histocompatibility gene cluster and is inherited tightly linked to the HLA-B*5701 allele.


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

Assisting a physician in developing a therapeutic management strategy for HIV-infected patients


Predicting likelihood of hypersensitivity reactions to abacavir in HIV-infected patients, based on the presence of the human leukocyte antigen HLA-B*5701 allele


Aiding in differentiating between true hypersensitivity to abacavir versus other underlying causes (eg, concomitant infection, reaction to other drugs, or inflammatory disease)

Interpretation Provides information to assist in interpretation of the test results

Positivity for human leukocyte antigen allele HLA-B*5701 confers high risk for hypersensitivity to abacavir.


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

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

Patients who have received a heterologous blood transfusion within the preceding 6 weeks, or who have received an allogeneic blood or marrow transplant, can have inaccurate genetic test results due to presence of donor DNA. Interpretation is more critical when there is a clinical history of, or when the physician suspects, an abacavir hypersensitivity reaction. Although the negative predictive value of the test is high, a negative HLA-B*5701 result does not preclude the development of an allergic response to abacavir and cannot substitute for clinical vigilance whenever abacavir therapy is administered. As symptoms of abacavir hypersensitivity are often nonspecific and can imitate other conditions commonly seen in HIV patients on antiviral therapy, the phenotypic diagnosis of abacavir hypersensitivity can be quite challenging. There is significant variability among patients identified as hypersensitive to abacavir.


Newly discovered rare HLA-B alleles are being reported in individuals and may result from gene conversion activities between HLA gene loci. This assay also detects closely related, but rare, alleles including *5708, *5710, *5713, *5714, *5715, *5716, and *5514. There are, as yet, no data indicating whether these subtypes are associated with hypersensitivity.


Not all individuals who are positive for HLA-B*5701 will have a hypersensitivity reaction.

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. Mallal S, Nolan D, C Witt, et al: Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet 2002;359:727-732

2. 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

3. 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

4. Mallal S, Phillips E, Carosi G, et al: HLA-B*5701 screening for hypersensitivity to abacavir. N.Engl J Med 2008;358:568-579

5. 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. 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention. July 22-25, 2007. Sydney. Abstract WEAB305)

6. Daly AK, Donaldson PT, Bhatnagar P, et al: HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nat Genet 2009;41:816-819