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.
- 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
- MeSH
- chování MeSH
- dospělí MeSH
- HIV protilátky analýza MeSH
- kontrola infekce statistika a číselné údaje MeSH
- lidé MeSH
- mladiství MeSH
- pilotní projekty MeSH
- riziko MeSH
- sliny MeSH
- vězni MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Geografické názvy
- Slovenská republika MeSH
- MeSH
- bisexualita MeSH
- HIV infekce epidemiologie imunologie prevence a kontrola MeSH
- HIV protilátky analýza MeSH
- homosexualita mužská MeSH
- kondomy využití MeSH
- lidé MeSH
- prevalence MeSH
- sliny imunologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Geografické názvy
- Slovenská republika MeSH
- MeSH
- glykoproteiny MeSH
- HIV infekce MeSH
- imunoanalýza MeSH
- lidé MeSH
- lidský herpesvirus 2 imunologie MeSH
- protilátky virové krev MeSH
- rizikové faktory MeSH
- virové proteiny diagnostické užití imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- biologické markery MeSH
- HIV séropozitivita imunologie MeSH
- lidé MeSH
- nádory imunologie MeSH
- Check Tag
- lidé MeSH
