PMID- 17479950
OWN - NLM
STAT- MEDLINE
DCOM- 20070611
LR  - 20171116
IS  - 1537-6591 (Electronic)
IS  - 1058-4838 (Linking)
VI  - 44
IP  - 11
DP  - 2007 Jun 1
TI  - A simple screening approach to reduce B*5701-associated abacavir hypersensitivity 
      on the basis of sequence variation in HIV reverse transcriptase.
PG  - 1503-8
AB  - BACKGROUND: Abacavir hypersensitivity is strongly associated with the human 
      leukocyte antigen (HLA)-B*5701 allele; however, the cost of routine 
      high-resolution HLA typing before initiation of therapy remains prohibitive. We 
      propose a simple approach to reduce B*5701-associated abacavir hypersensitivity 
      based on the screening of human immunodeficiency virus (HIV) reverse 
      transcriptase (RT) for a signature B*5701-associated cytotoxic T lymphocyte 
      escape mutation at RT codon 245. METHODS: The correlation between HLA-B*5701 and 
      RT codon 245 variation was investigated in 392 HIV-infected, antiretroviral-naive 
      adults who were initiating highly active antiretroviral therapy. The relationship 
      between codon 245 variation and premature abacavir discontinuation was 
      investigated in a larger cohort of treated individuals (n=982). Associations 
      between HLA-B*5701 and codon 245 variants were determined using Fisher's exact 
      test or the chi (2) test. RESULTS: A very strong association between HLA-B*5701 
      and RT codon 245 variation was observed. Only 1 (4.2%) of 24 subjects with B*5701 
      harbored virus with the clade B "wild-type" amino acid 245V, compared with 278 
      (75.5%) of 368 who did not have B*5701 (P<.001). The sensitivity and specificity 
      of codon 245 substitutions for predicting HLA-B*5701 were 96% and 75%, 
      respectively, and the positive and negative predictive values were 20% and 99.6%, 
      respectively. This association remained robust even after antiretroviral 
      treatment was administered (negative predictive value, 100%; n=269). In 
      abacavir-treated individuals (n=982), codon 245 substitutions were predictive of 
      premature abacavir discontinuation (P=.02). CONCLUSIONS: As HIV RT sequence is 
      incidentally obtained as a part of routine drug-resistance testing, the 
      examination of sequence variation at RT codon 245 could be adopted as a simple, 
      low-cost screening method to identify individuals who could be safely treated 
      with abacavir and/or who could benefit from HLA characterization.
FAU - Chui, Celia K S
AU  - Chui CK
AD  - British Columbia Centre for Excellence in HIV/AIDS, University of British 
      Columbia, Vancouver, Canada.
FAU - Brumme, Zabrina L
AU  - Brumme ZL
FAU - Brumme, Chanson J
AU  - Brumme CJ
FAU - Yip, Benita
AU  - Yip B
FAU - Phillips, Elizabeth J
AU  - Phillips EJ
FAU - Montaner, Julio S G
AU  - Montaner JS
FAU - Harrigan, P Richard
AU  - Harrigan PR
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070418
PL  - United States
TA  - Clin Infect Dis
JT  - Clinical infectious diseases : an official publication of the Infectious Diseases 
      Society of America
JID - 9203213
RN  - 0 (Anti-HIV Agents)
RN  - 0 (Dideoxynucleosides)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*57:01 antigen)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - WR2TIP26VS (abacavir)
SB  - IM
CIN - Clin Infect Dis. 2007 Nov 1;45(9):1243-4; author reply 1244-5. PMID: 17918094
MH  - Adult
MH  - Alleles
MH  - Anti-HIV Agents/*adverse effects
MH  - Antiretroviral Therapy, Highly Active/adverse effects
MH  - Contraindications
MH  - Dideoxynucleosides/*adverse effects
MH  - Drug Hypersensitivity/*genetics
MH  - Female
MH  - Genetic Testing/economics/*methods
MH  - Genotype
MH  - HIV Reverse Transcriptase/antagonists & inhibitors/chemistry/*genetics
MH  - HLA-B Antigens/*genetics
MH  - Humans
MH  - Male
MH  - Mutation
MH  - Prevalence
MH  - Reverse Transcriptase Inhibitors/*adverse effects
MH  - Sensitivity and Specificity
MH  - Sequence Analysis, RNA
EDAT- 2007/05/08 09:00
MHDA- 2007/06/15 09:00
CRDT- 2007/05/08 09:00
PHST- 2006/11/02 00:00 [received]
PHST- 2007/02/12 00:00 [accepted]
PHST- 2007/05/08 09:00 [pubmed]
PHST- 2007/06/15 09:00 [medline]
PHST- 2007/05/08 09:00 [entrez]
AID - CID41502 [pii]
AID - 10.1086/517499 [doi]
PST - ppublish
SO  - Clin Infect Dis. 2007 Jun 1;44(11):1503-8. doi: 10.1086/517499. Epub 2007 Apr 18.