Primary resistance to integrase strand-transfer inhibitors in Europe
Por:
Casadella, M, van Ham, PM, Noguera-Julian, M, van Kessel, A, Pou, C, Hofstra, LM, Santos, JR, Garcia, F, Struck, D, Alexiev, I, Kran, AMB, Hoepelman, AI, Kostrikis, LG, Somogyi, S, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paraskevis, D, Poljak, M, Puchhammer-Stockl, E, Stanekova, D, Stanojevic, M, Van Laethem, K, Lepej, SZ, Clotet, B, Boucher, CAB, Paredes, R, Wensing, AMJ, Domingo P., SPREAD Programme
Publicada:
1 oct 2015
Resumen:
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.
Filiaciones:
Casadella, M:
Univ Autonoma Barcelona, IrsiCaixa AIDS Res Inst, Badalona, Catalonia, Spain
van Ham, PM:
Utrecht Med Ctr, Dept Virol, Med Microbiol, Utrecht, Netherlands
Noguera-Julian, M:
Univ Autonoma Barcelona, IrsiCaixa AIDS Res Inst, Badalona, Catalonia, Spain
Univ Vic, Univ Cent Catalunya, Vic, Spain
van Kessel, A:
Utrecht Med Ctr, Dept Virol, Med Microbiol, Utrecht, Netherlands
Pou, C:
Univ Autonoma Barcelona, IrsiCaixa AIDS Res Inst, Badalona, Catalonia, Spain
Hofstra, LM:
Utrecht Med Ctr, Dept Virol, Med Microbiol, Utrecht, Netherlands
Luxembourg Inst Hlth, Lab Retrovirol, Luxembourg, Luxembourg
Santos, JR:
Univ Autonoma Barcelona, Hosp Univ Germans Trias & Pujol, HIV Unit, Badalona, Catalonia, Spain
Garcia, F:
Complejo Hosp Univ Granada, Inst Invest IBS, Cohorte Adultos Red Invest SIDA CoRIS, Granada, Spain
Alexiev, I:
Natl Ctr Infect & Parasit Dis, Sofia, Bulgaria
Kran, AMB:
Inst Clin Med, Oslo, Norway
Hoepelman, AI:
Utrecht Med Ctr, Dept Virol, Med Microbiol, Utrecht, Netherlands
Kostrikis, LG:
Univ Cyprus, Nicosia, Cyprus
Somogyi, S:
Robert Koch Inst, Berlin, Germany
Liitsola, K:
Natl Inst Hlth & Welf, Helsinki, Finland
Linka, M:
Natl Inst Publ Hlth, Natl Reference Lab HIV AIDS, Prague, Czech Republic
Nielsen, C:
Statens Serum Inst, DK-2300 Copenhagen, Denmark
Otelea, D:
Natl Inst Infect Dis Prof Dr Matei Bals, Bucharest, Romania
Paraskevis, D:
Univ Athens, Natl Retrovirus Reference Ctr, Athens, Greece
Poljak, M:
Univ Ljubljana, Fac Med, Slovenian HIV AIDS Reference Ctr, Ljubljana, Slovenia
Puchhammer-Stockl, E:
Univ Vienna, Vienna, Austria
Stanekova, D:
Slovak Med Univ, Bratislava, Slovakia
Stanojevic, M:
Univ Belgrade, Fac Med, Belgrade, Serbia
Van Laethem, K:
Katholieke Univ Leuven, Dept Microbiol & Immunol, Rega Inst Med Res, Clin & Epidemiol Virol, Leuven, Belgium
Lepej, SZ:
Univ Hosp Infect Dis Dr Fran Mihaljevic, Zagreb, Croatia
Clotet, B:
Univ Autonoma Barcelona, IrsiCaixa AIDS Res Inst, Badalona, Catalonia, Spain
Univ Vic, Univ Cent Catalunya, Vic, Spain
Luxembourg Inst Hlth, Lab Retrovirol, Luxembourg, Luxembourg
Boucher, CAB:
Erasmus MC, Dept Virol, Rotterdam, Netherlands
Paredes, R:
Univ Autonoma Barcelona, IrsiCaixa AIDS Res Inst, Badalona, Catalonia, Spain
Univ Vic, Univ Cent Catalunya, Vic, Spain
Luxembourg Inst Hlth, Lab Retrovirol, Luxembourg, Luxembourg
Wensing, AMJ:
Utrecht Med Ctr, Dept Virol, Med Microbiol, Utrecht, Netherlands
Domingo P.:
Institut d’Investigació Biomèdica Sant Pau (IIB SANT PAU), Sant Quintí 77-79, 08041 Barcelona, Spain
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