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Primary resistance to integrase strand-transfer inhibitors in Europe
M. Casadellà, PM. van Ham, M. Noguera-Julian, A. van Kessel, C. Pou, LM. Hofstra, JR. Santos, F. Garcia, D. Struck, I. Alexiev, AM. Bakken Kran, AI. Hoepelman, LG. Kostrikis, S. Somogyi, K. Liitsola, M. Linka, C. Nielsen, D. Otelea, D....
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články, multicentrická studie, práce podpořená grantem
NLK
Free Medical Journals
od 1996 do Před 1 rokem
Open Access Digital Library
od 1996-01-01
PubMed
26188038
DOI
10.1093/jac/dkv202
Knihovny.cz E-zdroje
- MeSH
- genetická variace MeSH
- genotyp MeSH
- HIV infekce farmakoterapie epidemiologie virologie MeSH
- HIV-1 účinky léků genetika MeSH
- HIV-integrasa genetika MeSH
- inhibitory HIV-integrasy farmakologie terapeutické užití MeSH
- lidé MeSH
- počet CD4 lymfocytů MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- sekvenční analýza DNA MeSH
- surveillance populace MeSH
- virová léková rezistence * MeSH
- virová nálož MeSH
- vysoce aktivní antiretrovirová terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
OBJECTIVES: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. METHODS: This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score ≥ 10 to at least one InSTI. To rule out circulation of minority InSTI-resistant HIV, 65 samples were selected for 454 integrase sequencing. RESULTS: For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIs were detected. Eleven (4%) subjects had mutations at resistance-associated positions with an HIVdb score ≥ 10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutations were detected, whereas integrase substitutions with an HIVdb score ≥ 10 were found in 8 (14.3%) individuals. CONCLUSIONS: No signature InSTI-resistant variants were circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistance were not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years.
Department of Virology Erasmus Medical Center Rotterdam The Netherlands
Department of Virology Medical Microbiology Utrecht Medical Centre Utrecht The Netherlands
Faculty of Medicine University of Belgrade Belgrade Serbia
Institute of Clinical Medicine Oslo Norway
IrsiCaixa AIDS Research Institute Universitat Autònoma de Barcelona Badalona Catalonia Spain
Laboratory of Retrovirology Luxembourg Institute of Health Luxembourg
National Center of Infectious and Parasitic Diseases Sofia Bulgaria
National Institute for Infectious Diseases 'Prof Dr Matei Bals' Bucharest Romania
National Institute of Health and Welfare Helsinki Finland
National Reference Laboratory for HIV AIDS National Institute of Public Health Prague Czech Republic
National Retrovirus Reference Center University of Athens Athens Greece
Robert Koch Institute Berlin Germany
Slovak Medical University Bratislava Slovakia
Slovenian HIV AIDS Reference Centre University of Ljubljana Faculty of Medicine Ljubljana Slovenia
Statens Serum Institut Copenhagen Denmark
University Hospital for Infectious Diseases 'Dr Fran Mihaljevic' Zagreb Croatia
Citace poskytuje Crossref.org
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