The Body Covers: The 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
Can HLA-B*5701 Testing Help Avoid Abacavir Hypersensitivity Reaction?
July 25, 2007
Retrospective analyses of abacavir (ABC, Ziagen)-treated individuals who have experienced hypersensitivity reaction (HSR) have suggested that the majority of these abacavir-related events, at least in white and Thai persons, occur in the presence of a familial haplotype involving the HLA-B*5701 allele. This allele can be rapidly and inexpensively identified through screening, which can help guide decisions about whether to use abacavir when designing an antiretroviral regimen.
The PREDICT-1 study1 prospectively evaluated the use of HLA-B*5701 testing in a group of abacavir-naive individuals commencing abacavir-based therapy. Individuals were randomized to begin abacavir without HLA testing (i.e., the standard of care) or to undergo HLA screening prior to abacavir initiation. Any HLA-B*5701-positive individuals identified in the screening arm were excluded from the use of abacavir. Individuals with a suspected HSR during abacavir therapy underwent a standardized patch test to immunologically confirm the HSR.
The study enrolled 1,956 abacavir-naive patients, but only 1,772 actually received at least one dose of abacavir-containing medication, thus constituting the "exposed" population. Among the exposed individuals, 84% were white, and 71% to 74% were male. In addition, the majority (81% to 82%) were treatment experienced.
The overall prevalence of HLA-B*5701 was 5.7%; 60% of these individuals were white, whereas less than 1% were black (one of 232 participants). Abacavir HSR was clinically diagnosed in 7.8% and 3.4% of individuals in the control and screened arms, respectively (P P < .0001). Risk factors for suspected HSR included white race, commencing a non-nucleoside reverse transcriptase inhibitor (NNRTI) simultaneously with abacavir and concurrent protease inhibitor (PI) use.
Although this study does not fully validate the HLA-B*5701 screening test across all racial groups, the data indicate that if testing for HLA-B*5701 becomes the standard of care, it could substantially reduce and possibly eliminate abacavir HSR while denying abacavir to only a very few individuals who test positive for HLA-B*5701. As such, the investigators argued that clinicians should consider screening for the HLA-B*5701 allele in any HIV-infected, abacavir-naive patient for whom abacavir therapy is being considered if validated screening methods are available.
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