Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV Cohort
Rauch, A., Nolan, D., Martin, A., McKinnon, E., Almeida, C. and Mallal, S. (2005) Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV Cohort. In: 7th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 13 - 16 November 2005, Dublin, Ireland.
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)-naive and ARTexperienced but abacavir-naive 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-naive 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.
|Publication Type:||Conference Item|
|Murdoch Affiliation:||Centre for Clinical Immunology and Biomedical Statistics|
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