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1. Primary resistance to integrase strand-transfer inhibitors in Europe

Author

Casadellà, M. van Ham, P.M. Noguera-Julian, M. van Kessel, A. Pou, C. Hofstra, L.M. Santos, J.R. Garcia, F. Struck, D. Alexiev, I. Bakken Kran, A.M. Hoepelman, A.I. Kostrikis, L.G. Somogyi, S. Liitsola, K. Linka, M. Nielsen, C. Otelea, D. Paraskevis, D. Poljak, M. Puchhammer-Stöckl, E. Staneková, D. Stanojevic, M. Van Laethem, K. Zidovec Lepej, S. Clotet, B. Boucher, C.A.B. Paredes, R. Wensing, A.M.J. Puchhammer-Stöckl, E. Sarcletti, M. Schmied, B. Geit, M. Balluch, G. Vandamme, A.M. Vercauteren, J. Derdelinckx, I. Sasse, A. Bogaert, M. Ceunen, H. De Roo, A. De Wit, S. Echahidi, F. Fransen, K. Goffard, J.C. Goubau, P. Goudeseune, E. Yombi, J.C. Lacor, P. Liesnard, C. Moutschen, M. Pierard, D. Rens, R. Schrooten, Y. Vaira, D. Vandekerckhove, L.P. Van den Heuvel, A. Van Der Gucht, B. Van Ranst, M. Van Wijngaerden, E. Vandercam, B. Vekemans, M. Verhofstede, C. Clumeck, N. Van Laethem, K. Beshkov, D. Alexiev, I. Zidovec Lepej, S. Begovac, J. Demetriades, I. Kousiappa, I. Demetriou, V. Hezka, J. Linka, M. Machala, L. Maly, M. Nielsen, C. Jørgensen, L.B. Gerstoft, J. Mathiesen, L. Pedersen, C. Nielsen, H. Laursen, A. Kvinesdal, B. Liitsola, K. Ristola, M. Suni, J. Sutinen, J. Hamouda, O. Kücherer, C. Berg, T. Braun, P. Poggensee, G. Däumer, M. Eberle, J. Heiken, H. Kaiser, R. Knechten, H. Korn, K. Müller, H. Neifer, S. Schmidt, B. Walter, H. Gunsenheimer-Bartmeyer, B. Harrer, T. Paraskevis, D. Hatzakis, A. Magiorkinis, E. Hatzitheodorou, E. Haida, C. Zavitsanou, A. Magiorkinis, G. Lazanas, M. Chini, M. Magafas, N. Tsogas, N. Paparizos, V. Kourkounti, S. Antoniadou, A. Papadopoulos, A. Panagopoulos, P. Poulakou, G. Sakka, V. Chryssos, G. Drimis, S. Gargalianos, P. Lelekis, M. Chilomenos, G. Psichogiou, M. Daikos, G.L. Sabatakou, H. Panos, G. Haratsis, G. Kordossis, T. Kontos, A. Koratzanis, G. Theodoridou, M. Mostrou, G. Spoulou, V. Schmit, J.C. Struck, D. Hemmer, R. Arendt, V. Staub, T. Schneider, F. Roman, F. Wensing, A.M. Boucher, C.A. van de Vijver, D.A. van Kessel, A. van, P.H. Brinkman, K. Op de, E.L. van der Ende, M.E. Hoepelman, I.M. van Kasteren, M. Juttmann, J. Kuipers, M. Langebeek, N. Richter, C. Santegoets, R.M. Schrijnders-Gudde, L. Schuurman, R. van de Ven, B.J. Åsjö, B. Bakken, A.M. Ormaasen, V. Aavitsland, P. Otelea, D. Paraschiv, S. Tudor, A.M. Jevtovic, D. Salemovic, D. Stanekova, D. Habekova, M. Mokras, M. Truska, P. Poljak, M. Lunar, M. Babic, D. Tomazic, J. Vidmar, L. Vovko, T. Karner, P. Clotet, B. Garcia, F. Domingo, P. Galindo, M.J. Miralles, C. Del, M.A. Ribera, E. Iribarren, J.A. Ruiz, L. de la Torre, J. Vidal, F. Garcia, F. Paredes, R. on behalf of the SPREAD programme

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.

Published
2015

2. Primary resistance to integrase strand-transfer inhibitors in Europe

Author

Moutschen, M., Casadellà, M., van Ham, P. M., Noguera-Julian, M., van Kessel, A., Pou, C., Hofstra, Laura Marije Arije, Santos, J. R., Garcia, F., Struck, D., Alexiev, Ivailo, Bakken Kran, A. M., Hoepelman, A. I., Kostrikis, Leontios G., Somogyi, Sybille, Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paraskevis, Dimitrios N., Poljak, M., Puchhammer-Stöckl, E., Staneková, D., Stanojevic, M., Van Laethem, K., Zidovec Lepej, S., Clotet, B., Boucher, C. A. B., Paredes, R., Wensing, A. M. J., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. C., Goubau, P., Goudeseune, E., Yombi, J. C., Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Beshkov, Danail, Begovac, J., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Machala, L., Maly, M., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Ristola, M., Suni, J., Sutinen, J., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Chilomenos, G., Psichogiou, Mina A., Daikos, George L., Sabatakou, H., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., Wensing, A. M., Boucher, C. A., van de Vijver, D. A., van, P. H., Brinkman, K., Op de, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M., Schrijnders-Gudde, L., Schuurman, R., van de Ven, B. J., Åsjö, Birgitta, Bakken, A. M., Ormaasen, V., Aavitsland, P., Paraschiv, S., Tudor, A. M., Jevtovic, D., Salemovic, D., Stanekova, D., Habekova, M., Mokráš, Miloš, Truska, P., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Domingo, P., Galindo, M. J., Miralles, C., Del, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de la Torre, J., Vidal, F., Kostrikis, Leontios G. [0000-0002-5340-7109], and Paraskevis, Dimitrios [0000-0001-6167-7152]

Subjects
sequence analysis, genotype, Human immunodeficiency virus 1, HIV Infections, RNA directed DNA polymerase inhibitor, integrase strand transfer inhibitor, HIV Integrase, molecular epidemiology, Human immunodeficiency virus prevalence, Risk Factors, Antiretroviral Therapy, Highly Active, genetic variability, genetics, Stanford HIVdb score, clinical trial, Human immunodeficiency virus infected patient, highly active antiretroviral therapy, Viral Load, unclassified drug, virology, health survey, dolutegravir, Europe, female, risk factor, Population Surveillance, virus gene, raltegravir, amino acid substitution, p31 integrase protein, Human immunodeficiency virus 1, DNA sequence, gene sequence, Article, male, antiviral resistance, Drug Resistance, Viral, proteinase inhibitor, Humans, cross-sectional study, controlled study, human, HIV Integrase Inhibitors, quality control, scoring system, CD4 lymphocyte count, integrase inhibitor, Sequence Analysis, DNA, virus load, nonnucleoside reverse transcriptase inhibitor, Human immunodeficiency virus 1 infection, major clinical study, drug efficacy, Cross-Sectional Studies, multicenter study, drug effects, genetic variation, HIV-1, integrase
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. 70 2885 2888 Cited By :15

Published
2015

3. Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

Author

Moutschen, M., Frentz, D., Van de Vijver, D. A. M. C., Abecasis, A. B., Albert, Jan, Hamouda, O., Jørgensen, L. B., Ku¨cherer, C., Struck, D., Schmit, J. -C, Vercauteren, J., A˚sjo¨, B., Balotta, Claudia, Beshkov, Danail, Camacho, Ricardo J., Clotet, B., Coughlan, S., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, Leontios G., Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paraskevis, Dimitrios N., Paredes, R., Poljak, M., Puchhammer, Stockl E., So¨nnerborg, A., Stanekova, D., Stanojevic, M., Van Wijngaerden, E., Wensing, A. M. J., Boucher, C. A. B., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. -M, Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Bruckova, M., Machala, L., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Salminen, M., Ristola, M., Suni, J., Sutinen, J., Berg, T., Braun, P., Poggensee, G., Da¨umer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Mu¨ller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Chilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Levi, I., Chemtob, D., Riva, C., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Kessel, A., van Bentum, P. H. M., Brinkman, K., op de Coul, E. L., van der Ende, M. E., Hoepelman, I., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R., Schrijnders-Gudde, L., Schuurman, R., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paixa&tild, o, T., Duque, V., Araújo, F., Jevtovic, D., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de la Torre, J., Vidal, F., Garcia, F., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Thalme, A., Nave´r, L., Bratt, G., Blaxhult, A., Gissle´n, M., Svennerholm, B., Bergbrant, I., Björkman, Per, Sa¨ll, C., Mellgren, A˚, Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Ma¨kitalo, S., o¨berg, S., Holmblad, P., Ho¨fer, M., Holmberg, H., Josefson, P., Ryding, U., Van Kessel, A., Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], Virology, Erasmus MC other, Frentz, Dineke, Van de Vijver, David A.M.C., Abecasis, Ana B., Albert, Jan, Hamouda, Osamah, Jørgensen, Louise B., Ku¨cherer, Claudia, Struck, Daniel, Schmit, Jean-Claude, Vercauteren, Jurgen, A˚sjo¨, Birgitta, Balotta, Claudia, Beshkov, Danail, Camacho, Ricardo J., Clotet, Bonaventura, Coughlan, Suzie, Griskevicius, Algirda, Grossman, Zehava, Horban, Andrzej, Kolupajeva, Tatjana, Korn, Klau, Kostrikis, Leondios G., Liitsola, Kirsi, Linka, Marek, Nielsen, Clau, Otelea, Dan, Paraskevis, Dimitrio, Paredes, Roger, Poljak, Mario, Puchhammer-Sto¨ckl, Elisabeth, So¨nnerborg, Ander, Stanekova, Danica, Stanojevic, Maja, Van Wijngaerden, Eric, Wensing, Annemarie M.J., Boucher, Charles A.B., SPREAD programme investigators, including Vitale F and Tramuto F., Graduate School, UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale, UCL - (SLuc) Service de microbiologie, UCL - (SLuc) Service de médecine interne générale, UCL - (SLuc) Service d'hématologie, Clinicum, and Department of Medicine

Subjects
Male, virus strain, Resistance, HIV Infections, Drug resistance, THERAPY, Nucleoside Reverse Transcriptase Inhibitor, ANTIRETROVIRAL DRUG-RESISTANCE, 0302 clinical medicine, Medical microbiology, Genotype, Medicine and Health Sciences, Prevalence, HIV Infection, 030212 general & internal medicine, UNITED-KINGDOM, Phylogeny, 0303 health sciences, Communicable disease, Transmission (medicine), adult, virus mutation, UPDATED RECOMMENDATIONS, virus transmission, 3. Good health, Europe, Infectious Diseases, female, risk factor, virus resistance, Female, NAIVE PATIENTS, SOCIETY-USA PANEL, Research Article, Human, Adult, medicine.medical_specialty, Anti-HIV Agents, Virus, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, male, MOLECULAR EPIDEMIOLOGY, Drug Resistance, Viral, medicine, proteinase inhibitor, Humans, Transmission, controlled study, human, molecular phylogeny, 030304 developmental biology, nonhuman, MUTATIONS, business.industry, Anti-HIV Agent, nucleotide sequence, nonnucleoside reverse transcriptase inhibitor, Human immunodeficiency virus 1 infection, Virology, major clinical study, unindexed sequence, Parasitology, 3121 General medicine, internal medicine and other clinical medicine, Mutation, HIV-1, business
Abstract

Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy.Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM.Conclusion: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring. © 2014 Frentz et al. licensee BioMed Central Ltd. 14 Cited By :16

Published
2014

4. Increase in transmitted resistance to non-nucleoside reverse transcriptase inhibitors among newly diagnosed HIV-1 infections in Europe

Author

Frentz, D. Van de Vijver, D.A.M.C. Abecasis, A.B. Albert, J. Hamouda, O. Jørgensen, L.B. Kücherer, C. Struck, D. Schmit, J.-C. Vercauteren, J. Åsjö, B. Balotta, C. Beshkov, D. Camacho, R.J. Clotet, B. Coughlan, S. Griskevicius, A. Grossman, Z. Horban, A. Kolupajeva, T. Korn, K. Kostrikis, L.G. Liitsola, K. Linka, M. Nielsen, C. Otelea, D. Paraskevis, D. Paredes, R. Poljak, M. Puchhammer-Stöckl, E. Sönnerborg, A. Stanekova, D. Stanojevic, M. Van Wijngaerden, E. Wensing, A.M.J. Boucher, C.A.B. Puchhammer-Stockl, E. Sarcletti, M. Schmied, B. Geit, M. Balluch, G. Vandamme, A.-M. Vercauteren, J. Derdelinckx, I. Sasse, A. Bogaert, M. Ceunen, H. De Roo, A. De Wit, S. Echahidi, F. Fransen, K. Goffard, J.-C. Goubau, P. Goudeseune, E. Yombi, J.-C. Lacor, P. Liesnard, C. Moutschen, M. Pierard, D. Rens, R. Schrooten, Y. Vaira, D. Vandekerckhove, L.P.R. Van den Heuvel, A. Van Der Gucht, B. Van Ranst, M. Vandercam, B. Vekemans, M. Verhofstede, C. Clumeck, N. Van Laethem, K. Demetriades, I. Kousiappa, I. Demetriou, V. Hezka, J. Bruckova, M. Linka, M. Machala, L. Nielsen, C. Jørgensen, L.B. Gerstoft, J. Mathiesen, L. Pedersen, C. Nielsen, H. Laursen, A. Kvinesdal, B. Salminen, M. Ristola, M. Liitsola, K. Suni, J. Sutinen, J. Korn, K. Kücherer, C. Berg, T. Braun, P. Poggensee, G. Däumer, M. Eberle, J. Heiken, H. Kaiser, R. Knechten, H. Müller, H. Neifer, S. Schmidt, B. Walter, H. Gunsenheimer-Bartmeyer, B. Harrer, T. Paraskevis, D. Hatzakis, A. Magiorkinis, E. Hatzitheodorou, E. Haida, C. Zavitsanou, A. Magiorkinis, G. Lazanas, M. Chini, M. Magafas, N. Tsogas, N. Paparizos, V. Kourkounti, S. Antoniadou, A. Papadopoulos, A. Panagopoulos, P. Poulakou, G. Sakka, V. Chryssos, G. Drimis, S. Gargalianos, P. Lelekis, M. Chilomenos, G. Psichogiou, M. Daikos, G.L. Panos, G. Haratsis, G. Kordossis, T. Kontos, A. Koratzanis, G. Theodoridou, M. Mostrou, G. Spoulou, V. Coughlan, S. De Gascun, C. Byrne, C. Duffy, M. Bergin, C. Reidy, D. Farrell, G. Lambert, J. O'Connor, E. Rochford, A. Low, J. Coakely, P. O'Dea, S. Hall, W. Grossman, Z. Levi, I. Chemtob, D. Balotta, C. Riva, C. Mussini, C. Caramma, I. Capetti, A. Colombo, M.C. Rossi, C. Prati, F. Tramuto, F. Vitale, F. Ciccozzi, M. Angarano, G. Rezza, G. Schmit, J.C. Struck, D. Hemmer, R. Arendt, V. Staub, T. Schneider, F. Roman, F. Wensing, A.M.J. Boucher, C.A.B. van Kessel, A. van Bentum, P.H.M. Brinkman, K. op de Coul, E.L. van der Ende, M.E. Hoepelman, I. van Kasteren, M. Juttmann, J. Kuipers, M. Langebeek, N. Richter, C. Santegoets, R. Schrijnders-Gudde, L. Schuurman, R. van de Ven, B.J.M. Åsjö, B. Ormaasen, V. Aavitsland, P. Horban, A. Stanczak, J.J. Stanczak, G.P. Firlag-Burkacka, E. Wiercinska-Drapalo, A. Jablonowska, E. Malolepsza, E. Leszczyszyn-Pynka, M. Szata, W. Camacho, R. Palma, C. Borges, F. Paixão, T. Duque, V. Araújo, F. Jevtovic, D. Salemovic, D. Stanekova, D. Habekova, M. Mokras, M. Truska, P. Poljak, M. Lunar, M. Babic, D. Tomazic, J. Vidmar, L. Vovko, T. Karner, P. Clotet, B. Domingo, P. Galindo, M.J. Miralles, C. del Pozo, M.A. Ribera, E. Iribarren, J.A. Ruiz, L. de la Torre, J. Vidal, F. Garcia, F. Paredes, R. Albert, J. Heidarian, A. Aperia-Peipke, K. Axelsson, M. Mild, M. Karlsson, A. Sönnerborg, A. Thalme, A. Navér, L. Bratt, G. Karlsson, A. Blaxhult, A. Gisslén, M. Svennerholm, B. Bergbrant, I. Björkman, P. Säll, C. Mellgren, Å. Lindholm, A. Kuylenstierna, N. Montelius, R. Azimi, F. Johansson, B. Carlsson, M. Johansson, E. Ljungberg, B. Ekvall, H. Strand, A. Mäkitalo, S. öberg, S. Holmblad, P. Höfer, M. Holmberg, H. Josefson, P. Ryding, U. on behalf of the SPREAD Programme

Abstract

Background: One out of ten newly diagnosed patients in Europe was infected with a virus carrying a drug resistant mutation. We analysed the patterns over time for transmitted drug resistance mutations (TDRM) using data from the European Spread program.Methods: Clinical, epidemiological and virological data from 4317 patients newly diagnosed with HIV-1 infection between 2002 and 2007 were analysed. Patients were enrolled using a pre-defined sampling strategy.Results: The overall prevalence of TDRM in this period was 8.9% (95% CI: 8.1-9.8). Interestingly, significant changes over time in TDRM caused by the different drug classes were found. Whereas nucleoside resistance mutations remained constant at 5%, a significant decline in protease inhibitors resistance mutations was observed, from 3.9% in 2002 to 1.6% in 2007 (p = 0.001). In contrast, resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) doubled from 2.0% in 2002 to 4.1% in 2007 (p = 0.004) with 58% of viral strains carrying a K103N mutation. Phylogenetic analysis showed that these temporal changes could not be explained by large clusters of TDRM.Conclusion: During the years 2002 to 2007 transmitted resistance to NNRTI has doubled to 4% in Europe. The frequent use of NNRTI in first-line regimens and the clinical impact of NNRTI mutations warrants continued monitoring. © 2014 Frentz et al.; licensee BioMed Central Ltd.

Published
2014

5. Limited cross-border infections in patients newly diagnosed with HIV in Europe

Author

Moutschen, M., Frentz, D., Wensing, A. M. J., Albert, Jan, Paraskevis, Dimitrios N., Abecasis, A. B., Hamouda, O., Jørgensen, L. B., Kücherer, C., Struck, D., Schmit, J. -C, Åsjö, Birgitta, Balotta, Claudia, Beshkov, Danail, Camacho, Ricardo J., Clotet, B., Coughlan, S., De Wit, S., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, Leontios G., Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Sönnerborg, A., Stanekova, D., Stanojevic, M., Vandamme, A. -M, Boucher, C. A. B., Van de Vijver, D. A. M. C., Balluch, G., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Bruckova, M., Machala, L., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Salminen, M., Ristola, M., Suni, J., Sutinen, J., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Chilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Levi, I., Chemtob, D., Franzetti, M., Lai, A., Binda, F., Tramuto, F., Ciccozzi, M., Mussini, C., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Kessel, A., van Bentum, P. H. M., Brinkman, K., de Coul, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., Schuurman, R., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Jevtovic, D., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de la Torre, J., Vidal, F., Garcia, F., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, Per, Säll, C., Mellgren, Å., Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., Ryding, U., Van Kessel, A., Instituto de Higiene e Medicina Tropical (IHMT), Centro de Malária e outras Doenças Tropicais (CMDT), Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Frentz, D, Wensing, AMJ, Albert, J, Paraskevis, D, Abecasis, AB, Hamouda, O, Jørgensen, LB, Kücherer, C, Struck, D, Schmit, JC, Åsjö, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, De Wit, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paredes, R, Poljak, M, Puchhammer-Stöckl, E, Sönnerborg, A, Stanekova, D, Stanojevic, M, Vandamme, AM, Boucher, CAB, Van de Vijver, DAMC, Tramuto, F, Van Wijngaerden, Eric, Van Ranst, Marc, Van Laethem, Kristel, Derdelinckx, Inge, Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], Virology, and Graduate School

Subjects
Male, Epidemiology, Human immunodeficiency virus (HIV), Human immunodeficiency virus 1, HIV Infections, medicine.disease_cause, Virologie générale, phylogeny, Settore MED/42 - Igiene Generale E Applicata, Men who have sex with men, EMERGENCE, 0302 clinical medicine, Medicine and Health Sciences, Medicine, Infection control, Cluster Analysis, 030212 general & internal medicine, Israel, Pathologie maladies infectieuses, travel, Phylogeny, 0303 health sciences, Molecular Epidemiology, Travel, Transmission (medicine), article, virus transmission, IMMUNODEFICIENCY-VIRUS TYPE-1, 3. Good health, Europe, female, Infectious Diseases, SUBTYPE B, DRUG-RESISTANT HIV-1, RNA, Viral, male homosexual, Adult, structural gene, Molecular Sequence Data, Newly diagnosed, Clusters, 03 medical and health sciences, male, SDG 3 - Good Health and Well-being, MOLECULAR EPIDEMIOLOGY, SWITZERLAND, Virology, geographic distribution, Humans, Transmission, In patient, human, 030304 developmental biology, nonhuman, Molecular epidemiology, business.industry, Research, high risk population, Virologie médicale, nucleotide sequence, Sequence Analysis, DNA, Human immunodeficiency virus 1 infection, major clinical study, unindexed sequence, 3121 General medicine, internal medicine and other clinical medicine, HIV-1, business, Europe, HIV-1, Transmission, Clusters, Demography, cluster analysis
Abstract

Background: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe.Results: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2013

6. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

Author

Moutschen, M., Theys, K., Deforche, K., Vercauteren, J., Libin, P., van de Vijver, D. A. M. C., Albert, Jan, Åsjö, Birgitta, Balotta, Claudia, Bruckova, M., Camacho, Ricardo J., Clotet, B., Coughlan, S., Grossman, Z., Hamouda, O., Horban, A., Korn, K., Kostrikis, Leontios G., Kücherer, C., Nielsen, C., Paraskevis, Dimitrios N., Poljak, M., Puchhammer-Stockl, E., Riva, C., Ruiz, L., Liitsola, K., Schmit, J. -C, Schuurman, R., Sönnerborg, A., Stanekova, D., Stanojevic, M., Struck, D., Van Laethem, K., Wensing, A. M. J., Boucher, C. A. B., Vandamme, A. M., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Linka, M., Machala, L., Jrgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Ristola, M., Suni, J., Sutinen, J., K̈ucherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Issaris, C., Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Xilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., Hall, W., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., Levi, I., Chemtob, D., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Bentum, P. H. M., Brinkman, K., op de Coul, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paix̃ao, T., Duque, V., Araújo, F., Jevtovic, D. J., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Babic, Dunja Z., Tomazic, J., Vidmar, L., Karner, P., Gutíerrez, C., deMendoza, C., Erkicia, I., Domingo, P., Camino, X., Galindo, M. J., Blanco, J. L., Leal, M., Masabeu, A., Guelar, A., Llibre, J. M., Margall, N., Iribarren, J. A., Gutierrez, S., Baldov́i, J. F., Pedreira, J. D., Gatell, J. M., Moreno, S., de Mendoza, C., Soriano, V., Blaxhult, A., Heidarian, A., Karlsson, A., Aperia-Peipke, K., Bergbrant, I. -M, Gissĺen, M., Svennerholm, M., Björkman, Per, Bratt, G., Carlsson, M., Ekvall, H., Ericsson, M., Ḧofer, M., Johansson, B., Sonnerb̈org, A., Kuylenstierna, N., Ljungberg, B., Mäkitalo, S., Strand, A., Öberg, S., Virology, Erasmus MC other, Van Wijngaerden, Eric, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Centro de Malária e outras Doenças Tropicais (CMDT), Graduate School, Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale, UCL - (SLuc) Service de microbiologie, UCL - (SLuc) Service de médecine interne générale, Theys, K, Deforche, K, Vercauteren, J, Libin, P, van de Vijver, DA, Albert, J, Asjö, B, Balotta, C, Bruckova, M, Camacho, RJ, Clotet, B, Coughlan, S, Grossman, Z, Hamouda, O, Horban, A, Korn, K, Kostrikis, LG, Kücherer, C, Nielsen, C, Paraskevis, D, Poljak, M, Puchhammer Stockl, E, Riva, C, Ruiz, L, Liitsola, K, Schmit, JC, Schuurman, R, Sönnerborg, A, Stanekova, D, Stanojevic, M, Struck, D, Van Laethem, K, Wensing, AM, Boucher, CA, Vandamme, AM, Tramuto, F, and Vitale, F

Subjects
Adult, Male, lcsh:Immunologic diseases. Allergy, Anti-HIV Agents, education, Virulence, HIV Infections, Drug resistance, Biology, Settore MED/42 - Igiene Generale E Applicata, Virus, polymorphism, 03 medical and health sciences, Viral Proteins, SDG 3 - Good Health and Well-being, Virology, Genotype, Drug Resistance, Viral, drug-naive, medicine, Humans, Prospective Studies, 030304 developmental biology, 0303 health sciences, Polymorphism, Genetic, 030306 microbiology, Research, protease, Viral Load, Reverse transcriptase, 3. Good health, CD4 Lymphocyte Count, Drug-naïve, Infectious Diseases, 3121 General medicine, internal medicine and other clinical medicine, Immunology, biology.protein, HIV-1, Female, Antibody, lcsh:RC581-607, Viral load, HIV-1 infected patient, medicine.drug, Peptide Hydrolases
Abstract

Background: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. Results: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. Conclusions: These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level. ispartof: Retrovirology vol:9 issue:1 ispartof: location:England status: published

Published
2012

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