Abacavir is an HIV reverse transcriptase inhibitor used in combination with other antivirals in the treatment of HIV infection. Its efficacy is equivalent to other HIV drugs, such as HIV protease inhibitors, and different combinations of drugs are used in clinical practice depending on patient response, side effects, and drug resistance profiles. Hypersensitivity reactions occur in approximately 5% of abacavir patients and are characterized by symptoms such as fever, rash, and acute respiratory symptoms, and can lead to potentially life-threatening hypotension if drug therapy is not discontinued (Clay, 2002). Veenstra (2004) noted that 2 studies had shown that patients with the HLA-B*5701 genotype are at greater risk of a hypersensitivity reaction, with an odds ratio of 117 (95% CI = 29-481) in 1 study (Mallal et al., 2002) and 23.6 (95% CI = 8-70) in another (Hetherington et al., 2002). Hughes et al. (2004) presented a cost-effectiveness analysis of HLA-B*5701 genotyping in preventing abacavir hypersensitivity.
Martin et al. (2004) reported that the combination of HLA-B*5701 and a haplotypic M493T polymorphism of HSP70-HOM (140559) is highly predictive of abacavir hypersensitivity.
Mallal et al. (2008) found that HLA-B*5701 screening reduced the risk of hypersensitivity reaction to abacavir used in the treatment of HIV infection.
In a genomewide association study of 51 patients with flucloxacillin-induced liver injury and 282 controls, Daly et al. (2009) found an association with rs2395029 in the MHC region (p = 8.7 x 10(-33)). The SNP is in complete linkage disequilibrium with HLA-B*5701. Further MHC genotyping of 64 flucloxacillin-tolerant controls confirmed the association with HLA-B*5701 (odds ratio of 80.6; p = 9.0 x 10(-19)). The association was replicated in a second cohort of 23 patients. In HLA-B*5701 carriers, rs10937275 in the ST6GAL1 (109675) gene on chromosome 3q also showed genomewide significance (odds ratio of 4.1; p = 1.4 x 10(-8)).
