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Abacavir Hypersensitivity - HLA Testing

Abacavir is a potent, tolerable, approved NRTI for HIV-1 infection. Hypersensitivity reaction (HSR) to abacavir is reported in approximately 8% of individuals and is fatal in rare cases.

Mallal et. al. found that HLA-B*5701 was present in 14 (78%) of the 18 patients with abacavir hypersensitivity, and in four (2%) of the 167 abacavir tolerant patients (odds ratio 117 [95% CI 29-481], p<0.0001), and the HLA-DR7 and HLA-DQ3 combination was found in 13 (72%) of hypersensitive and five (3%) of tolerant patients (OR 73 [20-268], p<0.0001 ). HLA-B*5701, HLA-DR7, and HLA-DQ3 were present in combination in 13 (72%) hypersensitive patients and none of the tolerant patients (OR 822 [43-15 675], p<0.0001).

Genetic screening may be associated with reduction in the incidence of abacavir hypersensitivity and rate of false-positive diagnosis of abacavir hypersensitivity.

Procedure

The Puget Sound Blood Center provides screening for HLA-B*5701, HLA-DR7, and HLA-DQ3 to evaluate risk of abacavir hypersensitivity. Average cost of the test is $200 per patient.

  • Puget Sound Blood Center order forms (different from the blood order forms) can be found in the lab folder near RN station. Under the Immunogenetics Laboratory section, check “Other” and write in “HLA-B*5701 Abacavir.”
  • Nurses will need to draw a yellow top (ACD) tube of whole blood.
  • Patient’s blood will be tested first for HLA-B*5701 and if positive, HLA-DR7 and HLA-DQ3 testing will be performed reflexively for further discrimination.
  • Call PSBC at 292-1860 with questions. Results should turn around in 1-2 days and will be faxed to the clinic.
  • If results are positive, be sure to flag this as:
    (1) an item on patient’s problem list AND
    (2) an “allergy” – e-mail Madison pharmacy at madrxref@u.washington.edu or allergy@u.washington.edu

Caveats

It is important to know the limitations of this testing:

• These HLA polymorphisms do not predict abacavir hypersensitivity with complete accuracy. In the literature, up to 22-78% of suspected cases of abacavir hypersensitivity were not positive for HLA-B*5701.

• Most reports to date comprise small sample sizes and were performed on Caucasian cohorts from Australia and United Kingdom. The performance of these tests in non-Caucasian populations are not well characterized. NOTE: prevalence of HLA-B*5701 is much lower (as low as <1%) in Asian and some African black populations.

• While this may serve as a screening test for abacavir-naïve individuals or as a confirmatory test for those with suspected hypersensitivity, this test should NOT be used to exclude hypersensitivity as a possibility or as a rationale for rechallenge in abacavir-exposed individuals, given the possible fatal results of rechallenging an individual with suspected abacavir hypersensitivity and the imperfect nature of this test.

References

Mallal S, Nolan D, Witt C, Masel G, Martin AM, Moore C, Sayer D, Castley A, Mamotte C, Maxwell D, James I, Christiansen FT. Association between presence of HLA-B*5701, HLA-DR7, and HLA-DQ3 and hypersensitivity to HIV-1 reverse-transcriptase inhibitor abacavir. Lancet. 2002 Mar 2;359(9308):727-32.

Rauch A, Nolan D, Martin A, McKinnon E, Almeida C, Mallal S. Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study. Clin Infect Dis. 2006 Jul 1;43(1):99-102. Epub 2006 May 26.

Stekler J, Maenza J, Stevens C, Holte S, Malhotra U, McElrath MJ, Corey L, Collier AC. Abacavir hypersensitivity reaction in primary HIV infection. AIDS. 2006 Jun 12;20(9):1269-74.