By Ed Susman
SYDNEY, AUSTRALIA -- July 26, 2007 -- A genetic test that can help guide treatment of patients with HIV infection has proved to be 100% effective in screening for individuals who are likely to have a hypersensitivity reaction to abacavir (Ziagen), researchers said here at the 4th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention.
The test for the HLA-B*5701 allele successfully identifies patients with HIV who should not receive abacavir -- a nucleoside reverse transcriptase inhibitor that is one of the top two choices as the backbone for treatment combinations, the researchers said.
"What we have found with this study is that we can tailor therapy based on the genetic makeup of the patient," said Simon Mallal, MD, Director of Immunology and Infectious Diseases, Murdoch University, Perth, Australia.
In the PREDICT-1 study, Dr. Mallal and an international team of researchers enrolled 1,956 patients; half were assigned to undergo no screening and were placed on an HIV regimen containing abacavir. The other half of participants underwent HLA-B*5701 screening. In this group, those who were negative for this gene received treatment with an abacavir-containing therapy, while those who were positive for this gene were eliminated from the study.
"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 abacavir and a non-nucleoside reverse transcriptase inhibitor -- which also can produce a rash -- are taken off both drugs when the rash occurs because clinicians are not sure which drug is the causative agent.
In the PREDICT-1 trial, the researchers found 66 cases (7.8%) among the 847 patients in the control arm that doctors suspected were hypersensitivity reactions. Testing showed that 3.4% of those patients actually had a reaction.
Among the patients who were prescreened for HLA-B*5701, 2.7% of the 842 cases were suspected of being hypersensitivity reactions, but none were found to be true reactions to abacavir.
"We had almost a perfect trial," Dr. Mallal said in his oral presentation July 25th. "None of the more than 800 patients who were screened and found negative for HLA-B*5701 reported a hypersensitivity reaction."
He said that the trial will help doctors in deciding if they want to prescribe abacavir, often as a combination pill 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.
Ziagen is a registered trademark of GlaxoSmithKline, which provided funding for this study.
[Presentation title: PREDICT-1: A Novel Randomised Prospective Study to Determine the Clinical Utility of HLA-B*5701 Screening to Reduce Abacavir Hypersensitivity in HIV-1 Infected Subjects (Study CNA106030). Abstract WESS101]
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