The Pharmaceutical Journal
Vol 268 No 7187 p274-79
2 March 2002

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The Lancet (www.thelancet.com)

Genetic test could identify risk of hypersensitivity to abacavir

Patienrs at risk of a hypersensitivity reaction to the antiretroviral drug abacavir (Ziagen) could be identified using genetic testing, researchers suggest.

Professor Simon Mallal, centre for clinical immunology and biomedical statistics, Royal Perth Hospital, Australia, and colleagues assessed the association between specific genetic factors and abacavir hypersensitivity in 185 patients infected with human immunodeficiency virus. About 5 per cent of patients treated with abacavir develop a hypersensitivity reaction, which can be fatal.

The researchers found that genetic susceptibility to abacavir hypersensitivity is carried on the MHC 57.1 gene region. Specifically, three alleles, HLA-B*5701, HLA-DR7 and HLA-DQ3 were present in more patients with abacavir hypersensitivity than those who were abacavir-tolerant. A combination of all three alleles was found in 72 per cent of the hypersensitive patients and none of the tolerant patients. The researchers suggest that HLA typing could be included in practice guidelines for prevention and management of abacavir hypersensitivity.

A future test, based on this research, could "allow for the safer use of this drug without inappropriate denial of access of its use." However, they note: "HLA typing at these alleles cannot be regarded as a screening test, and current clinical practices should continue to underpin the management of abacavir hypersensitivity." They add that further studies are needed to assess the value of such a test in different ethnic populations (Lancet 2002;359:727).

In an accompanying commentary, Dr Amalio Telenti, University Hospital, Lausanne, says that although decisions about therapy based on genotype profiles might seem far-fetched, the identification of these few relevant genes are "just the first drops before the downpour" (ibid, p722).