Title

 

Authors

C. Dello Russo¹, L. Lisi¹, S. Di Giambenedetto², R. Cauda², and P. Navarra¹.
 
1 Institute of Pharmacology, Catholic University Medical School, Rome, Italy
2 Institute of Clinical Infectious Diseases, Catholic University Medical School, Rome, Italy

 

Abstract

BACKGROUND: International HIV treatment guidelines recommend HLA-B*57:01 typing before abacavir (ABC) administration, in order to reduce the incidence of ABC hypersensitivity reaction, the major cause of early therapy discontinuation. Recently, the screening has been also included in the license of ABC-containing products. Different technologies are available to detect individual HLA types that are routinely used for characterization of tissue compatibility during organ transplantation, such as DNA sequence-based typing (SBT) or sequence specific oligonucleotide probe (SSOP) method with additional DNA sequencing for patients screened as positive with the probes. However, these approaches are time consuming, expensive and not readily available. Alternative methods have been developed and validated, and used as more rapid screening tests of HLA-B*57:01 positive patients. These methods are based on identification of the HLA-B*57:01 allele by sequence specific primers (SSP) and semi-quantitative PCR. Considering that most of the standard semi-quantitative PCR techniques have been replaced by real-time (Q)-PCR, we have validated an alternative screening test based on the SSP method but using Q-PCR to detect the amplification products [Dello Russo et al., 2011]. In the present study, data from the use of the test into routine clinical practice are presented. During the validation procedure, genotyping obtained by this  new test were in complete (100%) agreement with a previous validated methodology, therefore the test has been used to screen HLA-B*57:01 patients of the Institute of Clinical Infectious Diseases, Catholic University Hospital ‘Policlinico Gemelli’, Rome. A total of 172 patients were genotyped, and 6.9 % were found HLA-B*57:01 positive carriers. Results from the genotyping have been used to make clinical therapeutic decisions. An analysis on possible adverse effects registered in the sub-group of patients effectively receiving ABC containing drugs is currently ongoing. In conclusion, in the present study, we implemented a novel HLA-B*57:01 screening test into routine clinical practice. Evidence presented would suggest that this test can be safely used in clinic settings and easily implemented by those laboratories already involved in detection of viral load, and virus genotyping.
 
Dello Russo C et al., (2011) Pharmacogenomics, in press.