Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir

Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruse...

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Vydáno v:The Journal of infectious diseases Ročník 204; číslo 11; s. 1811
Hlavní autoři: Canducci, Filippo, Ceresola, Elisa R, Boeri, Enzo, Spagnuolo, Vincenzo, Cossarini, Francesca, Castagna, Antonella, Lazzarin, Adriano, Clementi, Massimo
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.12.2011
Témata:
Amino Acid Substitution - genetics
Anti-HIV Agents - pharmacology
Drug Resistance, Viral - genetics
Heterocyclic Compounds, 3-Ring - pharmacology
HIV Infections - drug therapy
HIV Infections - virology
HIV Integrase - genetics
HIV Integrase Inhibitors - pharmacology
HIV-1 - drug effects
HIV-1 - enzymology
HIV-1 - genetics
Humans
Inhibitory Concentration 50
Microbial Sensitivity Tests
Mutation
Phenotype
Pyrrolidinones - pharmacology
Raltegravir Potassium
ISSN:1537-6613, 1537-6613
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Abstract Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruses obtained from 11 patients failing previous raltegravir-containing regimens. Dolutegravir maintained its activity in vitro on viruses with mutations in position 143 and 155. However, viruses with mutation Q148R associated with secondary mutations and the combination Q148H+G140S were instead associated with a reduced level of susceptibility to dolutegravir in vitro.
AbstractList Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruses obtained from 11 patients failing previous raltegravir-containing regimens. Dolutegravir maintained its activity in vitro on viruses with mutations in position 143 and 155. However, viruses with mutation Q148R associated with secondary mutations and the combination Q148H+G140S were instead associated with a reduced level of susceptibility to dolutegravir in vitro.Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruses obtained from 11 patients failing previous raltegravir-containing regimens. Dolutegravir maintained its activity in vitro on viruses with mutations in position 143 and 155. However, viruses with mutation Q148R associated with secondary mutations and the combination Q148H+G140S were instead associated with a reduced level of susceptibility to dolutegravir in vitro.
Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage within this class of antiretroviral drugs. Ex vivo phenotypic assays were conducted on 11 wild-type and 27 fully replicating recombinant viruses obtained from 11 patients failing previous raltegravir-containing regimens. Dolutegravir maintained its activity in vitro on viruses with mutations in position 143 and 155. However, viruses with mutation Q148R associated with secondary mutations and the combination Q148H+G140S were instead associated with a reduced level of susceptibility to dolutegravir in vitro.
Author Ceresola, Elisa R
Cossarini, Francesca
Canducci, Filippo
Spagnuolo, Vincenzo
Lazzarin, Adriano
Boeri, Enzo
Clementi, Massimo
Castagna, Antonella
Author_xml – sequence: 1
  givenname: Filippo
  surname: Canducci
  fullname: Canducci, Filippo
  email: canducci.filippo@hsr.it
  organization: Vita-Salute San Raffaele University, Laboratory of Virology and Microbiology, Milan, Italy. canducci.filippo@hsr.it
– sequence: 2
  givenname: Elisa R
  surname: Ceresola
  fullname: Ceresola, Elisa R
– sequence: 3
  givenname: Enzo
  surname: Boeri
  fullname: Boeri, Enzo
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  surname: Spagnuolo
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  surname: Cossarini
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  surname: Lazzarin
  fullname: Lazzarin, Adriano
– sequence: 8
  givenname: Massimo
  surname: Clementi
  fullname: Clementi, Massimo
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Snippet Novel integrase inhibitors are in advanced clinical development, and cross-resistance data are needed to consider the possibility to plan a sequential usage...
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SubjectTerms Amino Acid Substitution - genetics
Anti-HIV Agents - pharmacology
Drug Resistance, Viral - genetics
Heterocyclic Compounds, 3-Ring - pharmacology
HIV Infections - drug therapy
HIV Infections - virology
HIV Integrase - genetics
HIV Integrase Inhibitors - pharmacology
HIV-1 - drug effects
HIV-1 - enzymology
HIV-1 - genetics
Humans
Inhibitory Concentration 50
Microbial Sensitivity Tests
Mutation
Phenotype
Pyrrolidinones - pharmacology
Raltegravir Potassium
Title Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir
URI https://www.ncbi.nlm.nih.gov/pubmed/21984737
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