Are mutations in HIV type-1 reverse transcriptase 245 codon predictive of abacavir hypersensitivity reaction?

Abstract

HLA-B*5701 is strongly related to abacavir hypersensitivity reactions (HSRs). Polymorphisms at position 245 of HIV type-1 (HIV-1) reverse transcriptase (RT) show an association with HLA-B*5701 suggesting that viral genotyping performed for antiretroviral drug resistance testing could reduce human leukocyte antigen (HLA) screening necessity to prevent abacavir HSR. To further test the validity of 245 codon analysis results for predicting HSR, we analysed 1,179 sequences from 752 HIV-1-infected patients. Mutant amino acid residues in RT 245 were found in 30.6% of sequences. Among 239 patients with multiple longitudinal genotypes, 245 residues varied in 37 (15.5%) from wild type to mutant and/or vice versa. All these changes appeared during antiretroviral treatment. A total of 15 out of 229 (6.5%) abacavir-treated patients developed a clinically confirmed HSR: all carried B subtypes. There was no significant difference in the prevalence of 245 mutants between abacavir-treated patients with HSR (27%) and those without (29%), even after limiting the analysis to subtype B carriers. The significant intraindividual variability of 245 residues and the lack of their association with clinically confirmed HSR argue against their use as viral genetic markers to exclude patients at risk for HSR.