AIM: International HIV treatment guidelines recommend HLA-B*57:01 typing before abacavir administration, in order to reduce the incidence of abacavir hypersensitivity reactions, the major cause of early therapy discontinuation. A fast, sensitive and specific test for HLA-B*57:01 detection has been developed in the present study. MATERIALS & METHODS: Two sets of sequence-specific primers were designed, and amplification rapidly detected by real-time PCR. RESULTS: A total of 108 samples were analyzed in a single-blind fashion, and 41 samples were identified as positive. Complete agreement, with κ = 1 (standard error = 0.0962, p < 0.0001), was found, with a validated methodology used in the EPI109367 clinical trial funded by GlaxoSmithKline, and consisting of low-resolution sequence-specific oligonucleotide PCR, followed by high-resolution sequence-specific oligonucleotide PCR carried out on the HLA-B*57-positive samples. CONCLUSION: We provided a detailed characterization of a novel HLA-B*57:01 screening test, which can be easily implemented by those laboratories already involved in the detection of viral load and virus genotyping. Original submitted 26 October 2010; Revision submitted 13 December 2010.
Novel sensitive, specific and rapid pharmacogenomic test for the prediction of abacavir hypersensitivity reaction: HLA-B*57:01 detection by real-time PCR / Dello Russo, C; Lisi, L; Lofaro, A; Di Giambenedetto, S; Federico, B; Madeddu, Giordano; Salerno, M; Mura, Maria Stella Anna; Pirazzoli, A; de Luca, A; Cauda, R; Navarra, P.. - In: PHARMACOGENOMICS. - ISSN 1462-2416. - 12:4(2011), pp. 567-576. [10.2217/pgs.10.208]
Novel sensitive, specific and rapid pharmacogenomic test for the prediction of abacavir hypersensitivity reaction: HLA-B*57:01 detection by real-time PCR
MADEDDU, Giordano;MURA, Maria Stella Anna;
2011-01-01
Abstract
AIM: International HIV treatment guidelines recommend HLA-B*57:01 typing before abacavir administration, in order to reduce the incidence of abacavir hypersensitivity reactions, the major cause of early therapy discontinuation. A fast, sensitive and specific test for HLA-B*57:01 detection has been developed in the present study. MATERIALS & METHODS: Two sets of sequence-specific primers were designed, and amplification rapidly detected by real-time PCR. RESULTS: A total of 108 samples were analyzed in a single-blind fashion, and 41 samples were identified as positive. Complete agreement, with κ = 1 (standard error = 0.0962, p < 0.0001), was found, with a validated methodology used in the EPI109367 clinical trial funded by GlaxoSmithKline, and consisting of low-resolution sequence-specific oligonucleotide PCR, followed by high-resolution sequence-specific oligonucleotide PCR carried out on the HLA-B*57-positive samples. CONCLUSION: We provided a detailed characterization of a novel HLA-B*57:01 screening test, which can be easily implemented by those laboratories already involved in the detection of viral load and virus genotyping. Original submitted 26 October 2010; Revision submitted 13 December 2010.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.