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| The Journal of antimicrobial chemotherapy. 2015 Jul 17. pii: dkv202. doi: 10.1093/jac/dkv202 |
| Primary resistance to integrase strand-transfer inhibitors in Europe. |
| Casadellà M1, van Ham PM2, Noguera-Julian M3, van Kessel A4, Pou C5, Hofstra LM6, Santos JR7, Garcia F8, Struck D9, Alexiev I10, Bakken Kran AM11, Hoepelman AI12, Kostrikis LG13, Somogyi S14, Liitsola K15, Linka M16, Nielsen C17, Otelea D18, Paraskevis D19, Poljak M20, Puchhammer-Stöckl E21, Staneková D22, Stanojevic M23, Van Laethem K24, Zidovec Lepej S25, Clotet B26, Boucher CA27, Paredes R28, Wensing AM29 |
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Abstract 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. |
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© The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com. |
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Publikations ID: 26188038 Quelle: öffnen |
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