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Refining abacavir hypersensitivity diagnoses using a structured clinical assessment and genetic testing in the Swiss HIV Cohort Study


Rauch, A; Nolan, D; Thurnheer, C; Fux, C; Cavassini, M; Chave, J P; Opravil, M; Phillips, E; Mallal, S; Furrer, H; Swiss HIV Cohort Study (2008). Refining abacavir hypersensitivity diagnoses using a structured clinical assessment and genetic testing in the Swiss HIV Cohort Study. Antiviral Therapy, 13(8):1019-1028.

Abstract

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 ≥2), uncertain (mean score ≥-1 and ≤1) and unlikely (mean score ≤-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.

Abstract

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 ≥2), uncertain (mean score ≥-1 and ≤1) and unlikely (mean score ≤-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.

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20 citations in Web of Science®
24 citations in Scopus®
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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Infectious Diseases
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2008
Deposited On:02 Feb 2009 16:20
Last Modified:06 Dec 2017 17:30
Publisher:International Medical Press
ISSN:1359-6535
Additional Information:Full text at http://www.infekt.ch/updown/documents/publ/2008/Rauch_2008_RefiningABChypersensitivityDiagnosis_AVT.pdf?PHPSESSID=9698afe55eed90828f0f483c814b6843

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