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Low-Level K65R Mutation in HIV-1 Reverse Transcriptase of Treatment-Experienced Patients Exposed to Abacavir or Didanosine

BACKGROUND:: Prior abacavir (ABC) or didanosine (ddI) therapy can result in the L74V/I or K65R mutation in HIV-1 reverse transcriptase. Preexisting K65R may have an impact on the treatment response to tenofovir disoproxil fumarate (TDF). METHODS:: An allele-specific polymerase chain reaction (AS-PCR... Full description

Journal Title: JAIDS Journal of Acquired Immune Deficiency Syndromes 2007, Vol.46(2), pp.174-180
Main Author: Svarovskaia, S, Evguenia
Other Authors: Margot, A, Nicolas , Bae, S, Andrew , Waters, M, Joshua , Goodman, D, Derrick , Zhong, D, Lijie , Borroto-Esoda, D, Katyna , Miller, D, Michael
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ID: ISSN: 1525-4135 ; DOI: 10.1097/QAI.0b013e31814258c0
Link: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&NEWS=n&CSC=Y&PAGE=fulltext&D=ovft&AN=00126334-200710010-00007
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title: Low-Level K65R Mutation in HIV-1 Reverse Transcriptase of Treatment-Experienced Patients Exposed to Abacavir or Didanosine
format: Article
creator:
  • Svarovskaia, S, Evguenia
  • Margot, A, Nicolas
  • Bae, S, Andrew
  • Waters, M, Joshua
  • Goodman, D, Derrick
  • Zhong, D, Lijie
  • Borroto-Esoda, D, Katyna
  • Miller, D, Michael
subjects:
  • Didanosine
  • Multivariate Analysis
  • Polymerase Chain Reaction
  • RNA-Directed DNA Polymerase
  • Tenofovir
  • Genotypes
  • Abacavir
  • Quantitation
  • Mutation
  • Thymidine
  • Human Immunodeficiency Virus 1
  • AIDS and HIV
  • Microorganisms & Parasites
  • Human Genetics
  • Methods
ispartof: JAIDS Journal of Acquired Immune Deficiency Syndromes, 2007, Vol.46(2), pp.174-180
description: BACKGROUND:: Prior abacavir (ABC) or didanosine (ddI) therapy can result in the L74V/I or K65R mutation in HIV-1 reverse transcriptase. Preexisting K65R may have an impact on the treatment response to tenofovir disoproxil fumarate (TDF). METHODS:: An allele-specific polymerase chain reaction (AS-PCR) assay was developed to detect K65R with a lower limit of quantitation of 0.5%. RESULTS:: Among baseline plasma samples from 63 treatment-naive patients, no K65R was detected by AS-PCR. Among baseline samples from 154 treatment-experienced patients, 8 had K65R and 44 had L74V/I by population sequencing. Low-level K65R was detected in an additional 11 patients by AS-PCR, 3 of whom subsequently developed full K65R. Baseline K65R correlated with absence of thymidine analog mutations (TAMs; P = 0.003) and use of ABC or ddI (P = 0.004). Patients with full or low-level K65R at baseline or with L74V/I showed a diminished TDF response. Multivariate analyses confirmed that multiple TAMs, K65R, and L74V/I were independent predictors of diminished TDF response. CONCLUSIONS:: Prior therapy with ABC or ddI can result in a population genotype that shows K65R or L74V/I but does not reveal low-level K65R present in some patients. Subsequent treatment intensification with TDF resulted in a poor virologic response and may result in expansion of the preexisting K65R mutant.
language:
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identifier: ISSN: 1525-4135 ; DOI: 10.1097/QAI.0b013e31814258c0
fulltext: fulltext
issn:
  • 1525-4135
  • 15254135
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titleLow-Level K65R Mutation in HIV-1 Reverse Transcriptase of Treatment-Experienced Patients Exposed to Abacavir or Didanosine
creatorSvarovskaia, S, Evguenia ; Margot, A, Nicolas ; Bae, S, Andrew ; Waters, M, Joshua ; Goodman, D, Derrick ; Zhong, D, Lijie ; Borroto-Esoda, D, Katyna ; Miller, D, Michael
ispartofJAIDS Journal of Acquired Immune Deficiency Syndromes, 2007, Vol.46(2), pp.174-180
identifierISSN: 1525-4135 ; DOI: 10.1097/QAI.0b013e31814258c0
descriptionBACKGROUND:: Prior abacavir (ABC) or didanosine (ddI) therapy can result in the L74V/I or K65R mutation in HIV-1 reverse transcriptase. Preexisting K65R may have an impact on the treatment response to tenofovir disoproxil fumarate (TDF). METHODS:: An allele-specific polymerase chain reaction (AS-PCR) assay was developed to detect K65R with a lower limit of quantitation of 0.5%. RESULTS:: Among baseline plasma samples from 63 treatment-naive patients, no K65R was detected by AS-PCR. Among baseline samples from 154 treatment-experienced patients, 8 had K65R and 44 had L74V/I by population sequencing. Low-level K65R was detected in an additional 11 patients by AS-PCR, 3 of whom subsequently developed full K65R. Baseline K65R correlated with absence of thymidine analog mutations (TAMs; P = 0.003) and use of ABC or ddI (P = 0.004). Patients with full or low-level K65R at baseline or with L74V/I showed a diminished TDF response. Multivariate analyses confirmed that multiple TAMs, K65R, and L74V/I were independent predictors of diminished TDF response. CONCLUSIONS:: Prior therapy with ABC or ddI can result in a population genotype that shows K65R or L74V/I but does not reveal low-level K65R present in some patients. Subsequent treatment intensification with TDF resulted in a poor virologic response and may result in expansion of the preexisting K65R mutant.
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subjectDidanosine ; Multivariate Analysis ; Polymerase Chain Reaction ; RNA-Directed DNA Polymerase ; Tenofovir ; Genotypes ; Abacavir ; Quantitation ; Mutation ; Thymidine ; Human Immunodeficiency Virus 1 ; AIDS and HIV ; Microorganisms & Parasites ; Human Genetics ; Methods;
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6Borroto-Esoda, D, Katyna
7Miller, D, Michael
titleLow-Level K65R Mutation in HIV-1 Reverse Transcriptase of Treatment-Experienced Patients Exposed to Abacavir or Didanosine
descriptionBACKGROUND:: Prior abacavir (ABC) or didanosine (ddI) therapy can result in the L74V/I or K65R mutation in HIV-1 reverse transcriptase. Preexisting K65R may have an impact on the treatment response to tenofovir disoproxil fumarate (TDF). METHODS:: An allele-specific polymerase chain reaction (AS-PCR) assay was developed to detect K65R with a lower limit of quantitation of 0.5%. RESULTS:: Among baseline plasma samples from 63 treatment-naive patients, no K65R was detected by AS-PCR. Among baseline samples from 154 treatment-experienced patients, 8 had K65R and 44 had L74V/I by population sequencing. Low-level K65R was detected in an additional 11 patients by AS-PCR, 3 of whom subsequently developed full K65R. Baseline K65R correlated with absence of thymidine analog mutations (TAMs; P = 0.003) and use of ABC or ddI (P = 0.004). Patients with full or low-level K65R at baseline or with L74V/I showed a diminished TDF response. Multivariate analyses confirmed that multiple TAMs, K65R, and L74V/I were independent predictors of diminished TDF response. CONCLUSIONS:: Prior therapy with ABC or ddI can result in a population genotype that shows K65R or L74V/I but does not reveal low-level K65R present in some patients. Subsequent treatment intensification with TDF resulted in a poor virologic response and may result in expansion of the preexisting K65R mutant.
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authorSvarovskaia, S, Evguenia ; Margot, A, Nicolas ; Bae, S, Andrew ; Waters, M, Joshua ; Goodman, D, Derrick ; Zhong, D, Lijie ; Borroto-Esoda, D, Katyna ; Miller, D, Michael
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abstractBACKGROUND:: Prior abacavir (ABC) or didanosine (ddI) therapy can result in the L74V/I or K65R mutation in HIV-1 reverse transcriptase. Preexisting K65R may have an impact on the treatment response to tenofovir disoproxil fumarate (TDF). METHODS:: An allele-specific polymerase chain reaction (AS-PCR) assay was developed to detect K65R with a lower limit of quantitation of 0.5%. RESULTS:: Among baseline plasma samples from 63 treatment-naive patients, no K65R was detected by AS-PCR. Among baseline samples from 154 treatment-experienced patients, 8 had K65R and 44 had L74V/I by population sequencing. Low-level K65R was detected in an additional 11 patients by AS-PCR, 3 of whom subsequently developed full K65R. Baseline K65R correlated with absence of thymidine analog mutations (TAMs; P = 0.003) and use of ABC or ddI (P = 0.004). Patients with full or low-level K65R at baseline or with L74V/I showed a diminished TDF response. Multivariate analyses confirmed that multiple TAMs, K65R, and L74V/I were independent predictors of diminished TDF response. CONCLUSIONS:: Prior therapy with ABC or ddI can result in a population genotype that shows K65R or L74V/I but does not reveal low-level K65R present in some patients. Subsequent treatment intensification with TDF resulted in a poor virologic response and may result in expansion of the preexisting K65R mutant.
pub© 2007 Lippincott Williams & Wilkins, Inc.
doi10.1097/QAI.0b013e31814258c0
date2007-10-01