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Amplification of Near Full-length HIV-1 Proviruses for Next-Generation Sequencing
Published on: October 16, 2018
Are mutations in HIV type-1 reverse transcriptase 245 codon predictive of abacavir hypersensitivity reaction?
Laura Bracciale1, Rosaria Santangelo, Iuri Fanti
1Institute of Clinical Infectious Disease, Catholic University of Sacred Heart, Rome, Italy. laura.bracciale@poste.it
Antiviral Therapy
|March 27, 2009
Summary
HIV-1 reverse transcriptase (RT) 245 codon analysis does not reliably predict abacavir hypersensitivity reactions (HSRs). Viral genotyping at this position is not recommended for excluding patients at risk for HSR.
Area of Science:
- Immunogenetics
- Virology
- Pharmacogenomics
Background:
- Human leukocyte antigen (HLA)-B*5701 is a strong predictor of abacavir hypersensitivity reactions (HSRs).
- Polymorphisms in HIV-1 reverse transcriptase (RT) at codon 245 have been suggested as a potential surrogate marker for HLA-B*5701, potentially reducing the need for HLA screening.
- This study investigates the utility of HIV-1 RT 245 codon analysis for predicting abacavir HSR.
Purpose of the Study:
- To evaluate the predictive value of HIV-1 reverse transcriptase (RT) 245 codon mutations for abacavir hypersensitivity reactions (HSRs).
- To determine if viral genotyping at RT position 245 can replace human leukocyte antigen (HLA) screening for abacavir HSR risk assessment.
Main Methods:
- Analysis of 1,179 HIV-1 sequences from 752 patients to assess RT 245 codon variations.
- Longitudinal genotype analysis in 239 patients to track changes in RT 245 residues during antiretroviral treatment.
- Comparison of RT 245 mutant prevalence in abacavir-treated patients with and without confirmed HSR, with stratification for HIV-1 subtype B.
Main Results:
- Mutant amino acid residues at RT position 245 were present in 30.6% of analyzed sequences.
- Significant intraindividual variability of RT 245 residues was observed, with changes occurring during treatment in 15.5% of patients with longitudinal data.
- No significant difference in the prevalence of 245 mutants was found between abacavir-treated patients who developed HSR (27%) and those who did not (29%), even when limited to subtype B.
Conclusions:
- Significant intraindividual variability in HIV-1 RT 245 residues complicates their use as stable biomarkers.
- The lack of association between RT 245 mutations and clinically confirmed abacavir HSR suggests they are not reliable predictors.
- Viral genotyping at RT position 245 is not recommended for excluding patients at risk of abacavir hypersensitivity reactions.
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