HLA-B*5701 test for abacavir hypersensitivity works equally well in black and white patients

A test to predict who will develop a severe allergic reaction to the anti-HIV drug abacavir is equally accurate in black and white patients, according to a study published in the April 1^st edition of Clinical Infectious Diseases. Every black and white patient with symptoms suggestive of a hypersensitivity reaction to abacavir confirmed by skin-patch testing had a positive HLA-B*5701 test. There had previously been concerns that the HLA-B*5701 tests was less accurate in black individuals than whites.

Abacavir (Ziagen, also in the combination pills Kivexa and Trizivir) is a potent antiretroviral drug that is a popular choice for first-line antiretroviral therapy. Its main disadvantage is a hypersensitivity reaction that occurs in between 5% - 8% of patients treated with the drug. Symptoms involve feeling generally unwell, fever, rash, and stomach problems. They quickly disappear if treatment with the drug is stopped, but recommencing treatment with abacavir after a hypersensitivity reaction can lead to a potentially fatal drop in blood pressure.

Allergy to abacavir is strongly associated with the presence of the HLA-B*5701 gene, and a test has been developed to monitor patients for its presence. It occurs with greater frequency in patients with a racial origin from northern Europe and is rare in patients of African ethnicity. Earlier research also suggests that the HLA-B*5701 test may be less accurate in black patients than white individuals.

Symptoms suggestive of allergy to abacavir can be caused by other anti-HIV drugs, and results from blinded clinical trials show that a significant number of patients who are not taking abacavir are diagnosed with having allergy to the drug.

Investigators from the US therefore performed a study to assess the accuracy of this test in black and white patients. The study was retrospective and involved two groups of patients. Patients in the first group all developed symptoms of an abacavir hypersensitivity reaction and had a skin-patch test to check for an allergic reaction to abacavir. This test exposes the skin to a small amount of abacavir to see if it provokes a reaction.

Patients with a negative skin-patch test were diagnosed as having a “clinically suspected” hypersensitivity reaction, and those with a positive skin-patch test as having an “immunologically confirmed” hypersensitivity reaction.

These patients were matched with a second group of patients that consisted of abacavir-treated individuals of the same race who had not developed symptoms of an allergic reaction to the drug. Blood samples were obtained from every patient in the study to test for the presence of the HLA-B*5701 gene.

A total of 130 white patients with a suspected hypersensitivity reaction were included in the study and 32% of these had a positive skin-patch test. Of the 69 black patients with symptoms suggestive of a hypersensitivity reaction, only 7% had a positive skin-patch test.

All the black and white patients with a positive skin-patch test – an immunologically confirmed hypersensitivity reaction – had a positive HLA-B*5701 test, a 100% sensitivity. The test had a 44% sensitivity amongst white patients and 14% sensitivity amongst black patients with a clinically suspected hypersensitivity reaction.

But 15 white patients with a suspected hypersensitivity reaction, but a negative skin-patch test, had a positive HLA-B*5701 test, as did eight control patients. Similarly, five black patients with symptoms of allergy to abacavir, but a negative skin patch test, as well as two control patients with no symptoms of hypersensitivity, had a positive HLA-B*5701 screen. The specificity of the HLA-B*5701 test was 96% in black patients and 99% in white patients.

“The presence of HLA-B*5701 is significantly associated with an abacavir hypersensitivity reaction regardless of race or case definition of abacavir hypersensitivity reaction”, comment the investigators. They conclude, “these findings support the generalizability of HLA-B*5701 screening for the prevention of abacavir hypersensitivity reactions in US white and black populations.”