@article{3060741,
    title = "Primary resistance to integrase strand-transfer inhibitors in Europe",
    author = "Casadellà, M. and van Ham, P.M. and Noguera-Julian, M. and van Kessel, A. and Pou, C. and Hofstra, L.M. and Santos, J.R. and Garcia, F. and Struck, D. and Alexiev, I. and Bakken Kran, A.M. and Hoepelman, A.I. and Kostrikis, L.G. and Somogyi, S. and Liitsola, K. and Linka, M. and Nielsen, C. and Otelea, D. and Paraskevis, D. and Poljak, M. and Puchhammer-Stöckl, E. and Staneková, D. and Stanojevic, M. and Van Laethem, K. and Zidovec Lepej, S. and Clotet, B. and Boucher, C.A.B. and Paredes, R. and Wensing, A.M.J. and Puchhammer-Stöckl, E. and Sarcletti, M. and Schmied, B. and Geit, M. and Balluch, G. and Vandamme, A.M. and Vercauteren, J. and Derdelinckx, I. and Sasse, A. and Bogaert, M. and Ceunen, H. and De Roo, A. and De Wit, S. and Echahidi, F. and Fransen, K. and Goffard, J.C. and Goubau, P. and Goudeseune, E. and Yombi, J.C. and Lacor, P. and Liesnard, C. and Moutschen, M. and Pierard, D. and Rens, R. and Schrooten, Y. and Vaira, D. and Vandekerckhove, L.P. and Van den Heuvel, A. and Van Der Gucht, B. and Van Ranst, M. and Van Wijngaerden, E. and Vandercam, B. and Vekemans, M. and Verhofstede, C. and Clumeck, N. and Van Laethem, K. and Beshkov, D. and Alexiev, I. and Zidovec Lepej, S. and Begovac, J. and Demetriades, I. and Kousiappa, I. and Demetriou, V. and Hezka, J. and Linka, M. and Machala, L. and Maly, M. and Nielsen, C. and Jørgensen, L.B. and Gerstoft, J. and Mathiesen, L. and Pedersen, C. and Nielsen, H. and Laursen, A. and Kvinesdal, B. and Liitsola, K. and Ristola, M. and Suni, J. and Sutinen, J. and Hamouda, O. and Kücherer, C. and Berg, T. and Braun, P. and Poggensee, G. and Däumer, M. and Eberle, J. and Heiken, H. and Kaiser, R. and Knechten, H. and Korn, K. and Müller, H. and Neifer, S. and Schmidt, B. and Walter, H. and Gunsenheimer-Bartmeyer, B. and Harrer, T. and Paraskevis, D. and Hatzakis, A. and Magiorkinis, E. and Hatzitheodorou, E. and Haida, C. and Zavitsanou, A. and Magiorkinis, G. and Lazanas, M. and Chini, M. and Magafas, N. and Tsogas, N. and Paparizos, V. and Kourkounti, S. and Antoniadou, A. and Papadopoulos, A. and Panagopoulos, P. and Poulakou, G. and Sakka, V. and Chryssos, G. and Drimis, S. and Gargalianos, P. and Lelekis, M. and Chilomenos, G. and Psichogiou, M. and Daikos, G.L. and Sabatakou, H. and Panos, G. and Haratsis, G. and Kordossis, T. and Kontos, A. and Koratzanis, G. and Theodoridou, M. and Mostrou, G. and Spoulou, V. and Schmit, J.C. and Struck, D. and Hemmer, R. and Arendt, V. and Staub, T. and Schneider, F. and Roman, F. and Wensing, A.M. and Boucher, C.A. and van de Vijver, D.A. and van Kessel, A. and van, P.H. and Brinkman, K. and Op de, E.L. and van der Ende, M.E. and Hoepelman, I.M. and van Kasteren, M. and Juttmann, J. and Kuipers, M. and Langebeek, N. and Richter, C. and Santegoets, R.M. and Schrijnders-Gudde, L. and Schuurman, R. and van de Ven, B.J. and Åsjö, B. and Bakken, A.M. and Ormaasen, V. and Aavitsland, P. and Otelea, D. and Paraschiv, S. and Tudor, A.M. and Jevtovic, D. and Salemovic, D. and Stanekova, D. and Habekova, M. and Mokras, M. and Truska, P. and Poljak, M. and Lunar, M. and Babic, D. and Tomazic, J. and Vidmar, L. and Vovko, T. and Karner, P. and Clotet, B. and Garcia, F. and Domingo, P. and Galindo, M.J. and Miralles, C. and Del, M.A. and Ribera, E. and Iribarren, J.A. and Ruiz, L. and de la Torre, J. and Vidal, F. and Garcia, F. and Paredes, R. and on behalf of the SPREAD programme",
    journal = "The Journal of antimicrobial chemotherapy",
    year = "2015",
    volume = "70",
    number = "10",
    pages = "2885-2888",
    publisher = "Oxford University Press",
    doi = "10.1093/jac/dkv202",
    keywords = "dolutegravir;  integrase;  integrase inhibitor;  integrase strand transfer inhibitor;  nonnucleoside reverse transcriptase inhibitor;  proteinase inhibitor;  raltegravir;  RNA directed DNA polymerase inhibitor;  unclassified drug;  integrase;  integrase inhibitor;  p31 integrase protein, Human immunodeficiency virus 1, amino acid substitution;  antiviral resistance;  Article;  controlled study;  cross-sectional study;  drug efficacy;  Europe;  female;  gene sequence;  genetic variability;  human;  Human immunodeficiency virus 1;  Human immunodeficiency virus 1 infection;  Human immunodeficiency virus infected patient;  Human immunodeficiency virus prevalence;  major clinical study;  male;  molecular epidemiology;  multicenter study;  quality control;  scoring system;  sequence analysis;  Stanford HIVdb score;  virus gene;  CD4 lymphocyte count;  clinical trial;  DNA sequence;  drug effects;  genetic variation;  genetics;  genotype;  health survey;  highly active antiretroviral therapy;  HIV Infections;  risk factor;  virology;  virus load, Antiretroviral Therapy, Highly Active;  CD4 Lymphocyte Count;  Cross-Sectional Studies;  Drug Resistance, Viral;  Europe;  Female;  Genetic Variation;  Genotype;  HIV Infections;  HIV Integrase;  HIV Integrase Inhibitors;  HIV-1;  Humans;  Male;  Population Surveillance;  Risk Factors;  Sequence Analysis, DNA;  Viral Load",
    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 InSTIresistant 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 InSTIswere detected. Eleven (4%) subjects hadmutations at resistance-associated positions with an HIVdb score =10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutationsweredetected, whereas integrase substitutionswithanHIVdbscore=10were found in8(14.3%) individuals. Conclusions:No signature InSTI-resistant variantswere circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistancewere 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. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved."
}