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Conference
"Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions" Dr. Simon Mallal (biography) English - 2005-11-19 - 28 minutes
(16 slides)
Summary : Objectives: Abacavir (ABC) treatment is associated with hypersensitivity reactions in ~8% of Caucasians, and is highly predicted by the presence of the HLA-B*5701 allele. We aimed to determine the incidence of abacavir hypersensitivity reactions (ABC-HSR) after the introduction of prospective HLA-B*5701 screening.
Methods: All antiretroviral therapy (ART)-naīve and ARTexperienced but abacavir-naīve patients starting a new NRTIbackbone regimen after January 2002 were included. HLA-typing was performed by sequence-based methods, with avoidance of ABC in HLA-B*5701-positive patients. ABC-HSR was assessed using standardised clinical criteria and adjunctive epicutaneous patch testing in all patients with <6 weeks of ABC exposure.
Results: ART-naīve patients: 44 (37%) of 120 HLA-B*5701- negative patients started ABC and in 2 of these, ABC was discontinued within 6 weeks (1 diarrhoea, 1 headache probably zidovudin-related). ABC was prescribed for 1 of 8 HLA-B*5701- positive patients (HLA results not reviewed prior to therapy) who developed ABC-HSR and had a positive patch test. ARTexperienced patients: 106 (64%) of 164 HLA-B*5701-negative patients started ABC and in 3 of these, ABC was discontinued within 6 weeks: 1 with non-specific symptoms of headache and cold sweats not responsive to ABC withdrawal; and 2 with symptoms attributed to efavirenz or nevirapine (1 nausea, 1 rash) associated with negative ABC-patch-tests. 2 of 14 HLA-B*5701- positive patients started ABC: 1 HLA results not reviewed, 1 informed choice based on absence of HLA-B57-associated ancestral haplotype markers and limited treatment options; both patients experienced ABC-HSR and had positive patch tests results. After introduction of HLA-B*5701 screening before starting ABC, ABC-HSR was experienced by 1.9% (95% CI of 0.4%-5.6%) of all patients and by 0% of HLA-B*5701 negative patients, compared with 7% ABC-HSR prior to genetic screening.
Conclusion: Avoiding ABC in patients carrying the susceptibility locus HLA-B*5701 by prospective genetic screening dramatically decreased the incidence of ABC-HSR in the Western Australian HIV Cohort.
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