Abstract
Background: The abacavir hypersensitivity reaction (ABC HSR) is a well characterised adverse event, affecting approx. 5% of individuals exposed to ABC in clinical trials. Retrospective analyses have identified several risk factors for ABC HSR: carriage of the HLA-B*5701 allele is the dominant risk factor. The PREDICT-1 study (ClinicalTrials.gov ID: NCT00340080) is designed to provide robust definitive data on the clinical utility of prognostic screening for HLA-B*5701.
Methods: 1806 ABC-naive adults from 356 centres in Europe/Australia will be randomised (1:1) blindly to receive an ABC containing regimen as part of Arm A: standard of care (SOC) (retrospective genetic screening) or Arm B: SOC plus prospective genetic screening (to exclude HLA-B*5701 carriers). Co-primary endpoints are incidence of (i) clinically suspected ABC HSR and (ii) clinically suspected plus immunologically confirmed ABC HSR. Immunologically confirmed ABC HSR will be determined 6 weeks following clinical diagnosis (ABC stopped at initial diagnosis) using epicutaneous patch testing (EPT) read by an Independent Committee.
Conclusions: This is the first randomised, blinded, prospective study designed to determine the clinical utility of screening for a specific pharmacogenetic marker, HLA-B*5701, in the management of HIV patients. This design could be adapted by others to assess the utility of pharmacogenetic screening and the use of other medicines. In the absence of definitive data from well designed clinical studies, GSK does not recommend routine use of prognostic screening for HLA-B*5701 outside of a clinical research setting. Pharmacovigilance remains the cornerstone of successful ABC risk management.