Genetic Test Predicts Dangerous Adverse Effect of Antiretroviral Drug

A genetic test developed for human immunodeficiency virus (HIV) patients has been shown to predict adverse effects of an antiretroviral drug.

There are basically two types of genetic variations that could be exploited in personalized medicine. The first are genetic mutations that cause disease or poor disease prognosis, and the others are mutations that influence the effectiveness of a particular drug.

The antiretroviral drug that can cause serious side effects is called abacavir (ziagen). The pharmaceutic company GlaxoSmithKline (GKS; Brentford, UK) developed the genetic test, which was examined in a study directed by David Goldstein at Duke University's (Durham, NC, USA) Center for HIV/AIDS Vaccine Immunology (CHAVI). Results of the study appeared in the July 19, 2007, online edition of the journal Science. GSK hopes that by testing potential patients, this potentially fatal adverse event can now be eradicated from antiretroviral therapy.

The human leukocyte antigen HLA-A and HLA-B are normally switched off by HIV, thus preventing the immune system from recognizing the virus as foreign. The presence of the HLA-B* 5701 genetic variation on genes controlling the human HLA has now been shown to cause hypersensitive reactions in patients taking ziagen. The regulator-approved, double-blinded study used to validate the effect of the HLA-B* 5701 allele on Ziagen should enable others to conduct their own trials and push genetic associations into the clinic--something that has been difficult in the past.

The study also identified three gene variants that help patients fight off the virus. One of the polymorphisms found is associated with the HLA-B* 5701 allelle. This genetic variation allows the body to have a strong immune response against the virus. A second polymorphism, which was found near the HLA-C gene, could be a better target for new therapies. The study suggested that for some individuals at least, HLA-C is involved in controlling HIV-1. This gene is not thought to be turned off by HIV-1 and might provide a powerful target for an AIDS vaccine.


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GlaxoSmithKline
Duke University
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