Background:  The HLA-B*5701 allele is highly predictive of abacavir (ABC) hypersensitivity reactions (HSR). However, HLA typing is expensive and labor-intensive and requires specialized laboratories. We assessed the utility of the HCP5-single nucleotide polymorphism (SNP) in the setting of ABC-HSR as this SNP is in high linkage disequilibrium with HLA-B*5701.
Methods:  The HCP5-SNP (rs2395029) was determined in 108 participants of the Swiss HIV Cohort Study (SHCS) who had stopped ABC due to suspected ABC-HSR. ABC-HSR-reactions were reassessed by 2 experienced HIV physicians blinded to the genotyping results and classified as ABC-HSR likely, uncertain, and unlikely based on the presence of rash, fever, concomitant symptoms, onset of symptoms and co-medication use. In addition, we determined the HCP5-SNP in a random sample of 259 SHCS-participants with available HLA typing results. Genotyping of HCP5 rs2395029 was done by TaqMan allelic discrimination. High-resolution HLA-typing was performed by sequence-based methods.
Results:  The HCP5 T>G variant was present in 34 of the 108 individuals with suspected ABC-HSR and 34 of 34 of these individuals carried the HLA*B5701-allele. One individual was homozygous for the rare allele (HCP5-GG) and also carried 2 copies of HLA*B5701. Conversely, none of the HLA*B5701^– individuals carried the HCP5 T>G variant. The HCP5 T>G variant was significantly more frequent in the 25 individuals with likely ABC-HSR as compared to the 50 individuals with uncertain diagnosis and to the 33 with unlikely ABC-HSR (80%, 28%, and 3% respectively, p <0.001). From the random sample of 259 SHCS participants, all 23 HLA*B5701⁺ individuals carried the HCP5 T>G variant. Only 3 (1%) of the 236 HLA*B5701^– individuals carried the HCP5 T>G variant (1 of these carried HLA*B5703). Overall, the sensitivity of the HCP5 T>G variant for carriage of HLA-B*5701 was 100% (95%CI 91 to 100%) and the specificity 99% (95%CI 97 to 100%).
Conclusions:  The HCP5 T>G variant was highly associated with ABC-HSR. This SNP identified all HLA-B*5701⁺ individuals and was absent in 99% of HLA-B*5701^– individuals. If the high sensitivity of HCP5 rs2395029 genotyping for HLA-B*5701 can be confirmed in other populations it could serve as a simple and cheap screening tool for predicting ABC-HSR particularly in settings where high-resolution HLA-typing is not available.