Refining abacavir hypersensitivity diagnoses using a structured clinical assessment and genetic testing in the Swiss HIV Cohort Study.
Details
Serval ID
serval:BIB_A2CC94AC8AF9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Refining abacavir hypersensitivity diagnoses using a structured clinical assessment and genetic testing in the Swiss HIV Cohort Study.
Journal
Antiviral Therapy
ISSN
1359-6535
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
13
Number
8
Pages
1019-1028
Language
english
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 > 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.
Keywords
Anti-HIV Agents/adverse effects, Anti-HIV Agents/therapeutic use, Cohort Studies, Dideoxynucleosides/adverse effects, Dideoxynucleosides/therapeutic use, Drug Hypersensitivity/diagnosis, Drug Hypersensitivity/genetics, Genetic Predisposition to Disease, Genetic Variation, HIV Infections/drug therapy, HIV Infections/epidemiology, HLA-B Antigens/genetics, Humans, Patch Tests, Switzerland/epidemiology
Pubmed
Web of science
Create date
15/10/2009 8:43
Last modification date
20/08/2019 15:08