Document Detail


Refining abacavir hypersensitivity diagnoses using a structured clinical assessment and genetic testing in the Swiss HIV Cohort Study.
MedLine Citation:
PMID:  19195327     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Andri Rauch; David Nolan; Christine Thurnheer; Christoph A Fux; Matthias Cavassini; Jean-Philippe Chave; Milos Opravil; Elizabeth Phillips; Simon Mallal; Hansjakob Furrer;
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Antiviral therapy     Volume:  13     ISSN:  1359-6535     ISO Abbreviation:  Antivir. Ther. (Lond.)     Publication Date:  2008  
Date Detail:
Created Date:  2009-02-06     Completed Date:  2009-04-08     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9815705     Medline TA:  Antivir Ther     Country:  England    
Other Details:
Languages:  eng     Pagination:  1019-28     Citation Subset:  IM    
Affiliation:
Department of Infectious Diseases, University Hospital Inselspital and University of Bern, Bern, Switzerland. andri.rauch@insel.ch
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MeSH Terms
Descriptor/Qualifier:
Anti-HIV Agents / adverse effects,  therapeutic use
Cohort Studies
Dideoxynucleosides / adverse effects*,  therapeutic use*
Drug Hypersensitivity / diagnosis*,  genetics*
Genetic Predisposition to Disease
Genetic Variation
HIV Infections / drug therapy*,  epidemiology
HLA-B Antigens / genetics
Humans
Patch Tests
Switzerland / epidemiology
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Dideoxynucleosides; 0/HLA-B Antigens; 0/HLA-B*5701 antigen, human; 0/abacavir

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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