PGx ABACAVIR

Hypersensitivity to the HIV drug abacavir is a serious side effect that limits the use of the compound. About 5–8% of patients develop a hypersensitivity reaction characterized by nonspecific gastrointestinal and respiratory symptoms, as well as fever and skin rashes. Although discontinuing the drug leads to a rapid resolution of symptoms, re-treatment is contraindicated due to the risk of life-threatening reactions. Hypersensitivity to abacavir is associated with the presence of the HLA-B*57:01 allele (prevalence in the population is approximately 5%). It is estimated that 48% to 61% of patients with this subtype will develop hypersensitivity to abacavir, compared to 0% to 4% of patients who are HLA-B*57:01 negative. Based on the findings of the PREDICT-1 study, HLA typing before the initiation of therapy significantly reduces the incidence of hypersensitivity reactions. According to the German Federal Institute for Drugs and Medical Devices (BfArM), every HIV-infected patient should be tested for the presence of the HLA-B*57:01 allele before starting treatment with abacavir. Patients who test positive for HLA-B*57:01 should not use abacavir, unless no other treatment options are available based on their treatment history and resistance testing results. The FDA has also included this correlation in the warnings section of the prescribing information (Ziagen® summary of product characteristics).

References

BfArM 2016, Abacavir – Hypersensitivitätsreaktion / Swen et al. 2011, Clin Pharmacol Ther 89:662 / Fachinformation Ziagen® / Tozzi V 2010, Antiviral Res 85:190 / Mallal et al. 2008, N Engl J Med 358:568 / Chessman et al. 2008, Immunity 28:822 / FDA Drug Safety Information