By Liz Highleyman

An estimated 3%-8% of patients who take the nucleoside reverse transcriptase inhibitor abacavir (Ziagen; also in the fixed-dose combination pills Epzicom and Trizivir) may develop a potentially severe allergic hypersensitivity reaction characterized by symptoms including skin rash, fever, gastrointestinal, and respiratory symptoms; this usually occurs within the first 6 weeks after starting the drug.

Individuals who experience such a reaction should not take abacavir again, since doing so can be life-threatening. Because of this risk, physicians usually recommended that patients stop taking abacavir if they have a suspected reaction, although this may lead some people to discontinue the drug unnecessarily.

A few years ago researchers discovered that a human genetic variation known as the HLA-B*5071 allele is strongly associated with susceptibility to abacavir hypersensitivity reactions. As previously reported, the PREDICT-1 study showed that a genetic test for HLA-B*5071 can accurately predict which patients are at risk for abacavir hypersensitivity, enabling them to avoid the drug.

The HLA-B*5701 variation is not distributed evenly among different racial groups, being most common among people of Northern European descent and less so among people of African descent.

But a new study, published in the April 1, 2008 issue of Clinical Infectious Diseases, indicates that the HLA-B*5701 genetic test is as accurate for predicting potential abacavir hypersensitivity in blacks as in whites.

Researchers with the Study of Hypersensitivity to Abacavir and Pharmacogenetic Evaluation (SHAPE) team analyzed white and black case patients, identified through a chart review, who had been diagnosed as having an abacavir hypersensitivity reaction based on clinical findings only (a clinically suspected reaction) or based on clinical findings plus a positive skin patch test result (an immunologically confirmed reaction). Control subjects were racially matched individuals who tolerated abacavir for at least 12 weeks without experiencing a hypersensitivity reaction.

Case patients and control subjects were tested for the presence of the HLA-B*5701 variation. Sensitivity, specificity, and odds ratios for the detection of HLA-B*5701 as a marker for an abacavir hypersensitivity reaction were calculated separately for white and black participants.

Results

Conclusion

Based on these results, the study authors concluded, "Although immunologically confirmed abacavir hypersensitivity reactions are uncommon in black persons, the 100% sensitivity of HLA-B*5701 as a marker for immunologically confirmed abacavir hypersensitivity reaction in both U.S. white and black patients suggests similar implications of the association between HLA-B*5701 positivity and risk of abacavir hypersensitivity reactions in both races.

These findings, they added, "support the generalizability of HLA-B*5701 screening for the prevention of abacavir hypersensitivity reactions in U.S. white and black populations."

Center for AIDS Research, University of Alabama at Birmingham, Birmingham, AL; GlaxoSmithKline, Research Triangle Park, NC; Atlanta Infectious Diseases Group Professional Corporation, Atlanta, GA; Research Institute, Springfield, MA; Denver Public Health, Denver, CP; Centres for Clinical Pharmacology and Infectious Diseases and Clinical Immunology and Biomedical Statistics, Royal Perth Hospital, Murdoch University, Perth, Australia.

5/02/08

Reference
M Saag, R Balu, E Phillips, and others. High Sensitivity of Human Leukocyte Antigen-B*5701 as a Marker for Immunologically Confirmed Abacavir Hypersensitivity in White and Black Patients. Clinical Infectious Diseases 46(7): 1111-1118. April 1, 2008.