PMID- 19320242
OWN - NLM
STAT- MEDLINE
DCOM- 20090414
LR  - 20151119
IS  - 1359-6535 (Print)
IS  - 1359-6535 (Linking)
VI  - 14
IP  - 1
DP  - 2009
TI  - Are mutations in HIV type-1 reverse transcriptase 245 codon predictive of 
      abacavir hypersensitivity reaction?
PG  - 99-101
AB  - BACKGROUND: HLA-B*5701 is strongly related to abacavir hypersensitivity reactions 
      (HSRs). Polymorphisms at position 245 of HIV type-1 (HIV-1) reverse transcriptase 
      (RT) show an association with HLA-B*5701 suggesting that viral genotyping 
      performed for antiretroviral drug resistance testing could reduce human leukocyte 
      antigen (HLA) screening necessity to prevent abacavir HSR. METHODS: To further 
      test the validity of 245 codon analysis results for predicting HSR, we analysed 
      1,179 sequences from 752 HIV-1-infected patients. RESULTS: Mutant amino acid 
      residues in RT 245 were found in 30.6% of sequences. Among 239 patients with 
      multiple longitudinal genotypes, 245 residues varied in 37 (15.5%) from wild type 
      to mutant and/or vice versa. All these changes appeared during antiretroviral 
      treatment. A total of 15 out of 229 (6.5%) abacavir-treated patients developed a 
      clinically confirmed HSR: all carried B subtypes. There was no significant 
      difference in the prevalence of 245 mutants between abacavir-treated patients 
      with HSR (27%) and those without (29%), even after limiting the analysis to 
      subtype B carriers. CONCLUSIONS: The significant intraindividual variability of 
      245 residues and the lack of their association with clinically confirmed HSR 
      argue against their use as viral genetic markers to exclude patients at risk for 
      HSR.
FAU - Bracciale, Laura
AU  - Bracciale L
AD  - Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, 
      Rome, Italy. laura.bracciale@poste.it
FAU - Santangelo, Rosaria
AU  - Santangelo R
FAU - Fanti, Iuri
AU  - Fanti I
FAU - Prosperi, Mattia
AU  - Prosperi M
FAU - Colafigli, Mauela
AU  - Colafigli M
FAU - Di Giambenedetto, Simona
AU  - Di Giambenedetto S
FAU - Marchetti, Simona
AU  - Marchetti S
FAU - Di Franco, Aldo
AU  - Di Franco A
FAU - Cauda, Roberto
AU  - Cauda R
FAU - De Luca, Andrea
AU  - De Luca A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Antivir Ther
JT  - Antiviral therapy
JID - 9815705
RN  - 0 (Biomarkers)
RN  - 0 (Dideoxynucleosides)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B*57:01 antigen)
RN  - 0 (RNA, Viral)
RN  - 0 (Reverse Transcriptase Inhibitors)
RN  - EC 2.7.7.- (reverse transcriptase, Human immunodeficiency virus 1)
RN  - EC 2.7.7.49 (HIV Reverse Transcriptase)
RN  - WR2TIP26VS (abacavir)
SB  - IM
MH  - Biomarkers
MH  - Dideoxynucleosides/*adverse effects/therapeutic use
MH  - *Drug Hypersensitivity
MH  - Drug Resistance, Viral/genetics
MH  - Genotype
MH  - HIV Infections/*drug therapy/genetics/*virology
MH  - HIV Reverse Transcriptase/*genetics
MH  - HIV-1/*genetics
MH  - HLA-B Antigens/genetics
MH  - Humans
MH  - Mutation
MH  - *Polymorphism, Genetic
MH  - RNA, Viral/*genetics
MH  - Reverse Transcriptase Inhibitors/*adverse effects/therapeutic use
MH  - Sequence Analysis, DNA
MH  - Sequence Analysis, RNA
EDAT- 2009/03/27 09:00
MHDA- 2009/04/15 09:00
CRDT- 2009/03/27 09:00
PHST- 2009/03/27 09:00 [entrez]
PHST- 2009/03/27 09:00 [pubmed]
PHST- 2009/04/15 09:00 [medline]
PST - ppublish
SO  - Antivir Ther. 2009;14(1):99-101.