IAS: Genetic Test Pinpoints Patients Who'll React to Abacavir

SYDNEY, July 25 -- A screening test can identify patients at risk of suffering a dangerous hypersensitivity reaction to abacavir (Ziagen), a mainstay in the treatment of HIV.

"What we have found with this study is that we can tailor therapy based on the genetic makeup of the patient," Simon Mallal, M.D., of Murdoch University in Perth, Australia, told attendees at the International AIDS Society meeting here.

Dr. Mallal and colleagues enrolled 1,956 patients in the PREDICT-1 study. Half were assigned to a group that received standard care - that is, no screening - and were placed on an HIV regimen containing abacavir, a nucleoside reverse transcriptase inhibitor.

The other half underwent genetic screening for the HLA-B*5701 allele. Those who were found to be positive for the allele were eliminated from the study; the rest received treatment with a regimen containing abacavir.

"The hypersensitivity reaction caused by abacavir makes people feel unwell, with gastrointestinal and other side effects, sometimes including a rash," said Dr. Mallal.

Often, he noted, patients who are given regimens containing non-nucleoside reverse transcriptase inhibitors - which also can produce a rash as a side effect - and abacavir are taken off both drugs when the rash occurs because clinicians aren't sure which drug is the causative agent.

In the trial, there were 66 instances among the 847 patients in the control arm that doctors felt were hypersensitivity reactions. Testing showed that 3.4% of those patients actually had the reaction.

Among the patients who were prescreened, 2.7% of the 842 patients were suspected of having hypersensitivity reactions, but none were found to have a true reaction to abacavir.

"We had almost a perfect trial," Dr. Mallal said. "None of the patients who were screened and found negative for HLA-B*5701 reported a hypersensitivity reaction."

He said that the trial should help doctors decide whether they want to prescribe abacavir, often as a combination with lamivudine. He said that the abacavir combination and Truvada, a combination of emtricitabine and tenofovir, are the main treatment choices in patients on highly active antiretroviral therapy.

He also noted that the hypersensitivity reaction appears to occur about 3% of the time. Some studies had suggested it occurs as often as 12% of the time.

Stefano Vella, M.D., director of Istituto Superiore di Sanita in Rome, and a former president of the IAS, said the test should be shown to be cost-effective before it becomes commonplace.

"We need to evaluate it further," he suggested. He said, however, that he thought the use of the test would give doctors more confidence in prescribing the drug.

The hypersensitivity reaction can be fatal, but Dr. Mallal said that severe reactions have only occurred when doctors have attempted to re-challenge patients who have already had an initial reaction to the drug.