Document Detail

Cross-resistance profile of the novel integrase inhibitor Dolutegravir (S/GSK1349572) using clonal viral variants selected in patients failing raltegravir.
MedLine Citation:
PMID:  21984737     Owner:  NLM     Status:  MEDLINE    
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.
Filippo Canducci; Elisa R Ceresola; Enzo Boeri; Vincenzo Spagnuolo; Francesca Cossarini; Antonella Castagna; Adriano Lazzarin; Massimo Clementi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-10-07
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  204     ISSN:  1537-6613     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-10-31     Completed Date:  2011-12-22     Revised Date:  2013-08-15    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1811-5     Citation Subset:  AIM; IM    
Vita-Salute San Raffaele University, Laboratory of Virology and Microbiology, Milan, Italy.
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MeSH Terms
Amino Acid Substitution / genetics
Anti-HIV Agents / pharmacology*
Drug Resistance, Viral / genetics*
HIV Infections / drug therapy*,  virology
HIV Integrase / genetics
HIV Integrase Inhibitors / pharmacology*
HIV-1 / drug effects*,  enzymology,  genetics*
Heterocyclic Compounds, 3-Ring / pharmacology*
Inhibitory Concentration 50
Microbial Sensitivity Tests
Pyrrolidinones / pharmacology
Reg. No./Substance:
0/Anti-HIV Agents; 0/HIV Integrase Inhibitors; 0/Heterocyclic Compounds, 3-Ring; 0/Pyrrolidinones; 22VKV8053U/raltegravir; DKO1W9H7M1/dolutegravir; EC 2.7.7.-/HIV Integrase

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