Refining abacavir hypersensitivity diagnoses using a structured clinical assessment and genetic testing in the Swiss HIV Cohort Study.
BACKGROUND
We aimed to assess the value of a structured clinical assessment and genetic testing for refining the diagnosis of abacavir hypersensitivity reactions (ABC-HSRs) in a routine clinical setting.


METHODS
We performed a diagnostic reassessment using a structured patient chart review in individuals who had stopped ABC because of suspected HSR. Two HIV physicians blinded to the human leukocyte antigen (HLA) typing results independently classified these individuals on a scale between 3 (ABC-HSR highly likely) and -3 (ABC-HSR highly unlikely). Scoring was based on symptoms, onset of symptoms and comedication use. Patients were classified as clinically likely (mean score > or =2), uncertain (mean score > or = -1 and < or = 1) and unlikely (mean score < or = -2). HLA typing was performed using sequence-based methods.


RESULTS
From 131 reassessed individuals, 27 (21%) were classified as likely, 43 (33%) as unlikely and 61 (47%) as uncertain ABC-HSR. Of the 131 individuals with suspected ABC-HSR, 31% were HLA-B*5701-positive compared with 1% of 140 ABC-tolerant controls (P < 0.001). HLA-B*5701 carriage rate was higher in individuals with likely ABC-HSR compared with those with uncertain or unlikely ABC-HSR (78%, 30% and 5%, respectively, P < 0.001). Only six (7%) HLA-B*5701-negative individuals were classified as likely HSR after reassessment.


CONCLUSIONS
HLA-B*5701 carriage is highly predictive of clinically diagnosed ABC-HSR. The high proportion of HLA-B*5701-negative individuals with minor symptoms among individuals with suspected HSR indicates overdiagnosis of ABC-HSR in the era preceding genetic screening. A structured clinical assessment and genetic testing could reduce the rate of inappropriate ABC discontinuation and identify individuals at high risk for ABC-HSR.
Rauch
Andri
A
Department of Infectious Diseases, University Hospital Inselspital and University of Bern, Bern, Switzerland. andri.rauch@insel.ch
Nolan
David
D
Thurnheer
Christine
C
Fux
Christoph A
CA
Cavassini
Matthias
M
Chave
Jean-Philippe
JP
Opravil
Milos
M
Phillips
Elizabeth
E
Mallal
Simon
S
Furrer
Hansjakob
H
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use*; D004342:Drug Hypersensitivity / Q000175:diagnosis* / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D010328:Patch Tests; D013557:Switzerland / Q000453:epidemiology; D000099227:Abacavir
D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D015235:HLA-B Antigens; D000099227:Abacavir; C484830:HLA-B*57:01 antigen