Genetic Tests Reveal Risk of Dangerous Reaction to AIDS Drug

Genetic testing can reveal whether a widely used AIDS drug is likely to trigger a life-threatening reaction that occurs in about 5 percent of all people who take it. The drug, known generically as abacavir, was approved in 1998 and is a mainstay of AIDS treatment, typically used in combination with other medicines. Doctors have long suspected that some genetic factor was involved in the adverse reaction, which typically occurs after patients have taken the drug for about two weeks. The latest finding should help doctors avoid this problem by screening patients in advance for the telltale gene.

Researchers found that a particular combination of genes that regulate the body's immune defenses makes people highly susceptible to the bad reaction. "It's a truly astonishing connection between a human genetic marker and the risk of a potentially fatal drug reaction," said Dr. Charles Flexner of Johns Hopkins University. The reports on the discovery were presented Wednesday at the Ninth Conference on Retroviruses and Opportunistic Infections in Seattle.

Dr. Simon Mallal, whose team located the genetic fingerprint at Royal Perth Hospital in Australia, said doctors there now routinely check for the gene before deciding whether to prescribe abacavir. The allergic-like reaction often involves severe vomiting, fever, rash, shortness of breath and muscle ache. The symptoms gradually go away when people stop taking abacavir. Its frequency varies, and it is rare in blacks. Mallal said it occurs in 9 percent of his patients. Screening for the gene HLA-B5701 should reduce adverse reactions to 2.5 percent without denying the drug to those who can safely take it.

It is unclear whether this gene truly causes the hypersensitivity or is passed along with some nearby gene that is the real culprit. Mallal cautioned that the gene does not explain all cases of hyperactivity. Doctors still need to follow patients carefully when prescribing the drug. Mallal's report will also be published in the Lancet (2002;359;9308).

Abacavir, made by GlaxoSmithKline, is sold as Ziagen and in combination with two older AIDS drugs, AZT and 3TC, as Trizivir. Dr. Seth Hetherington, the company's chief of AIDS drug development, presented similar findings implicating the immune system gene in the drug hypersensitivity.

Back to other CDC news for February 28, 2002

Previous Updates