Individuals with the HLA-B*5701 Genetic Variation Have More Abacavir Hypersensitivity Symptoms

By Liz Highleyman

Abacavir (Ziagen) hypersensitivity reactions occur in 3% to 8% of patients starting the drug. The reaction may be characterized by fever, skin rash, gastrointestinal (GI), and respiratory symptoms, but these vary widely from person to person.

Researchers have shown that people who carry the HLA-B*5701 genetic variation are more likely to experience this reaction. A newly developed genetic test accurately predicts which patients are at risk for the reaction and therefore should not take abacavir.

In the present study, presented last week at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) in Chicago (September 17-20, 2007), researchers analyzed the clinical presentation of hypersensitivity symptoms and their relationship with HLA-B*5701 status.

A total of 198 subjects with clinically suspected abacavir hypersensitivity reactions (cases) were identified through chart reviews as a part of the SHAPE study (ABC107442). Cases must have had hypersensitivity symptoms in at least 2 categories (fever, rash, GI, or constitutional) with onset 6 weeks or less after initiating abacavir. All clinically-suspected abacavir hypersensitivity reaction cases then underwent abacavir skin patch testing and HLA-B*5701 evaluation.

Clinical symptoms of abacavir hypersensitivity reaction were summarized by HLA-B*5701 status. While Blacks and Whites were analyzed separately in SHAPE (since Blacks are less likely to carry the HLA-B*5701 variation), the descriptive results below are combined across race.

Results

• Patients who were HLA-B*5701 positive were more like to report fever (87% vs 56%) and constitutional symptoms (85% vs 73%) than HLA-B*5701 negative subjects.

• Further, HLA-B*5701 positive subjects more often had symptoms in 3 or more categories (82% vs 61%).

• Though suspected hypersensitivity symptoms occurred after a median of 7 days in both groups, everyone in the HLA-B*5701 positive group who experienced symptoms did so within a about a month.

• 94% of HLA-B*5701 positive subjects had onset of hypersensitivity reaction symptoms within 21 days of initiating abacavir.

• In contrast, some HLA-B*5701 negative patients had suspected hypersensitivity symptoms more than a year after starting abacavir, suggesting that the drug was unlikely to be the cause.

• Study results are summarized in the table below:

HSR = hypersensitivity reaction
SPT = skin patch test

Conclusion

"Subjects who carry the HLA-B*5701 allele are more likely than those without the allele to present with fever, and to have 3 or more categories of abacavir hypersensitivity reaction symptoms," the investigators concluded. "All HLA-B*5701 positive subjects had onset of abacavir hypersensitivity reaction symptoms within 34 days of starting abacavir use."

They added that, "HLA-B*5701 is a highly sensitive marker for skin patch test-positive abacavir hypersensitivity reaction; subjects who are HLA-B*5701negative are unlikely to have a positive skin patch test result."

09/25/07

Reference
C Martorell, M Saag, G Blick, and others. Clinical Presentation of Hypersensitivity Reaction to Abacavir (ABC HSR) by HLA-B*5701 Status. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, September 17-20, 2007. Abstract H-374.