PREDICT-1: a novel randomised prospective study to determine the clinical utility of HLA-B*5701 screening to reduce abacavir hypersensitivity in HIV-1 infected subjects

Objective: Retrospective analyses have identified several risk factors for abacavir (ABC) HSR, however carriage of the HLA-B*5701 allele is the dominant risk factor. The PREDICT-1 study (clinicaltrials.gov identifier NCT00340080) was designed to provide robust and definitive data on the clinical utility of prospective screening for HLA-B*5701 on the incidence of ABC HSR. Methods: ABC-naive adults from 314 centres in Europe/Australia were randomised (1:1) to receive an ABC containing regimen according to standard of care [SOC] (retrospective pharmacogenetic screening) or SOC plus prospective pharmacogenetic screening (to exclude HLA-B*5701 carriers). Co-primary endpoints are incidence of (i) clinically suspected ABC HSR and (ii) clinically suspected ABC HSR with immunological confirmation. Immunologically confirmed ABC HSR was determined approximately 6 weeks following initial clinical diagnosis (ABC stopped at initial diagnosis) using epicutaneous patch testing (EPT). EPT results were evaluated by an Independent Committee. Results: 1956 patients were randomised. Baseline characteristics were similar between the two study arms. The incidence of both clinically diagnosed and immunologically confirmed HSR was significantly lower in the prospective screening arm compared with the control arm; no cases of immunologically confirmed HSR were observed in the prospective screening arm. Conclusion: The results from this landmark study demonstrate that prospective HLA-B*5701 screening results in a dramatic, clinically relevant and statistically significant reduction in abacavir HSR. The PREDICT-1 study provides the high level of evidence required to support the implementation of HLA-B*5701 screening into routine clinical practice and is the first randomised, blinded and powered study to validate pharmacogenetic screening as a clinical tool to personalise therapy.