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IAS 2007: Sydney, Australia; July 22-25

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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.

PREDICT-1: Study Design
Click to enlarge
Adapted from Simon Mallal, M.D., et al.
Prospective analysis of such screening in clinical cohorts from Australia and the United Kingdom, where this test is now in fairly routine use, suggests that excluding HLA-B*5701-positive individuals from abacavir use leads to substantial reductions in the number of observed HSR events.

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.


Factor Associated With Abacavir HSR, OR (P Value)Abacavir HSR
Clinically SuspectedImmunologically ConfirmedClinically Suspected but Not Immunologically Confirmed
Prospective HLA-B*5701 screening vs. control0.40 (< .0001)0.03 (< .000001)0.69 (.1513)
White vs. non-white2.19 (.0242)4.21 (.2239)2.00 (.0879)
Introduction of NNRTI: yes vs. no3.19 (.0011)1.45 (.5693)4.04 (.0008)
Concurrent PI use: yes vs. no1.86 (.0094)1.05 (.9123)2.38 (.0031)

OR = odds ratio.


The sensitivity and specificity of immunologically confirmed HSR following HLA-B*5701 screening was 100% and 97%, respectively. In accord, the negative predicted value of HLA-B*5701 screening for immunologically confirmed HSR was 100%. Abacavir tolerance for up to six weeks or more is known to occur in some HLA-B*5701-positive individuals; thus, the positive predictive value of immunologically confirmed HSR following HLA-B*5701 screening was only 48%.

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.


Footnote

  1. Mallal S, Phillips E, Carosi G, et al. 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). In: Program and abstracts of the 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; July 22-25, 2007; Sydney, Australia. Abstract WESS101.



  
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