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3. Molecular epidemiology analysis of SARS-CoV-2 strains circulating in romania during the first months of the pandemic

Author

Surleac, M. Banica, L. Casangiu, C. Cotic, M. Florea, D. Sandulescu, O. Milu, P. Streinu-Cercel, A. Vlaicu, O. Paraskevis, D. Paraschiv, S. Otelea, D.

Abstract

BACKGROUND: The spread of SARS-CoV-2 generated an unprecedented global public health crisis. Soon after Asia, Europe was seriously affected. Many countries, including Romania, adopted lockdown measures to limit the outbreak. AIM: We performed a molecular epidemiology analysis of SARS-CoV-2 viral strains circulating in Romania during the first two months of the epidemic in order to detect mutation profiles and phylogenetic relatedness. METHODS: Respiratory samples were directly used for shotgun sequencing. RESULTS: All Romanian sequences belonged to lineage B, with a different subtype distribution between northern and southern regions (subtype B.1.5 and B.1.1). Phylogenetic analysis suggested that the Romanian epidemic started with multiple introduction events from other European countries followed by local transmission. Phylogenetic links between northern Romania and Spain, Austria, Scotland and Russia were observed, as well as between southern Romania and Switzerland, Italy, France and Turkey. One viral strain presented a previously unreported mutation in the Nsp2 gene, namely K489E. Epidemiologically-defined clusters displayed specific mutations, suggesting molecular signatures for strains coming from areas that were isolated during the lockdown. CONCLUSIONS: Romanian epidemic was initiated by multiple introductions from European countries followed by local transmissions. Different subtype distribution between northern and southern Romania was observed after two months of the pandemic. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2020

5. Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

Author

Colagrossi, L. Hermans, L.E. Salpini, R. Di Carlo, D. Pas, S.D. Alvarez, M. Ben-Ari, Z. Boland, G. Bruzzone, B. Coppola, N. Seguin-Devaux, C. Dyda, T. Garcia, F. Kaiser, R. Köse, S. Krarup, H. Lazarevic, I. Lunar, M.M. Maylin, S. Micheli, V. Mor, O. Paraschiv, S. Paraskevis, D. Poljak, M. Puchhammer-Stöckl, E. Simon, F. Stanojevic, M. Stene-Johansen, K. Tihic, N. Trimoulet, P. Verheyen, J. Vince, A. Lepej, S.Z. Weis, N. Yalcinkaya, T. Boucher, C.A.B. Wensing, A.M.J. Perno, C.F. Svicher, V. HEPVIR working group of the European Society for translational antiviral research (ESAR)

Abstract

Background: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. Methods: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. Results: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties. Conclusions: Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence. © 2018 The Author(s).

Published
2018

7. HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012

Author

Pineda-Peña, AC, Theys, K, Stylianou, D C, Demetriades, I, Puchhammer, E, Vandamme, AM, Aleksiev, I, Lepej, SZ, Linka, M, Fonager, J, Liitsola, K, Kaiser, R, Hamouda, O, Paraskevis, D, Coughlan, S, Grossman, Z, Mor, O, Zazzi, M, Griskevicius, A, Lipnickiene, V, Devaux, C, Boucher, Charles, Hofstra, M, Wensing, A, Bakken-Kran, AM, Horban, A, Camacho, R, Paraschiv, S, Otelea, D, Stanojevic, M, Stanekova, D, Poljak, M, Garcia, F, Paredes, R, Albert, J, Abecasis, AB, Kostrikis, LG, Pineda-Peña, AC, Theys, K, Stylianou, D C, Demetriades, I, Puchhammer, E, Vandamme, AM, Aleksiev, I, Lepej, SZ, Linka, M, Fonager, J, Liitsola, K, Kaiser, R, Hamouda, O, Paraskevis, D, Coughlan, S, Grossman, Z, Mor, O, Zazzi, M, Griskevicius, A, Lipnickiene, V, Devaux, C, Boucher, Charles, Hofstra, M, Wensing, A, Bakken-Kran, AM, Horban, A, Camacho, R, Paraschiv, S, Otelea, D, Stanojevic, M, Stanekova, D, Poljak, M, Garcia, F, Paredes, R, Albert, J, Abecasis, AB, and Kostrikis, LG

Published
2018

8. Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

Author

Colagrossi, L, Hermans, Lucas, Salpini, R, Di Carlo, D, Pas, Suzan, Alvarez, M, Ben-Ari, Z, Boland, G, Bruzzone, B, Coppola, N, Seguin-Devaux, C, Dyda, T, Garcia, F, Kaiser, R, Kose, S, Krarup, H, Lazarevic, I, Lunar, MM, Maylin, S, Micheli, V, Mor, O, Paraschiv, S, Paraskevis, D, Poljak, M, Puchhammer-Stockl, E, Simon, F, Stanojevic, M, Stene-Johansen, K, Tihic, N, Trimoulet, P, Verheyen, J, Vince, A, Lepej, SZ, Weis, N, Yalcinkaya, T, Boucher, Charles, Wensing, AMJ, Perno, CF, Svicher, V, Colagrossi, L, Hermans, Lucas, Salpini, R, Di Carlo, D, Pas, Suzan, Alvarez, M, Ben-Ari, Z, Boland, G, Bruzzone, B, Coppola, N, Seguin-Devaux, C, Dyda, T, Garcia, F, Kaiser, R, Kose, S, Krarup, H, Lazarevic, I, Lunar, MM, Maylin, S, Micheli, V, Mor, O, Paraschiv, S, Paraskevis, D, Poljak, M, Puchhammer-Stockl, E, Simon, F, Stanojevic, M, Stene-Johansen, K, Tihic, N, Trimoulet, P, Verheyen, J, Vince, A, Lepej, SZ, Weis, N, Yalcinkaya, T, Boucher, Charles, Wensing, AMJ, Perno, CF, and Svicher, V

Published
2018

9. HIV-1 sub-subtype F1 outbreak among MSM in Belgium

Author

Vinken, L, Fransen, K, Pineda-Peña, A C, Alexiev, I, Balotta, C, Debaisieux, L, Devaux, C, García Ribas, S, Gomes, P, Incardona, F, Kaiser, R, Ruelle, J, Sayan, M, Paraschiv, S, Paredes, R, Peeters, M, Sonnerborg, A, Vancutsem, E, Van den Wijngaert, S, Van Ranst, M, Verhofstede, C, Vandamme, A-M, Lemey, P, Van Laethem, K, Faculty of Sciences and Bioengineering Sciences, UGENT VUB Alliance Research Group in Information Systems, Faculty of Medicine and Pharmacy, Supporting clinical sciences, Microbiology and Infection Control, Clinical Biology, Department of Bio-engineering Sciences, Faculty of Law and Criminology, and Fundamental rights centre

Abstract

HIV-1 non-B subtype infections have been observed in Belgium since the 1980s. However, subtype B predominates amongst men having sex with men (MSM), whereas other subtypes are mainly associated with sub-Saharan African migrants and heterosexual risk behavior. In the last decade, subtype F1 diagnoses have increased substantially in Belgium, representing 9% of newly diagnosed and therapy-naïve HIV-1 patients linked to care in 2014. In the present study, the Belgian subtype F1 epidemic has been characterized within a global context, where F1 is responsible for

Published
2017
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10. A21 HIV-1 sub-subtype F1 outbreak among MSM in Belgium

Author

Vinken, L., Fransen, K., Pineda-Peña, A.C., Alexiev, I., Balotta, C., Debaisieux, L., Devaux, C., García Ribas, S., Gomes, P., Incardona, F., Kaiser, R, Ruelle, J., Sayan, M., Paraschiv, S., Paredes, Roger, Peeters, M., Sonnerborg, A., Vancutsem, E., Van den Wijngaert, S., Van Ranst, M., Verhofstede, C., Vandamme, A.-M., Lemey, P., Van Laethem, K., and Universitat Autònoma de Barcelona

Published
2017

11. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

Author

Hofstra, L.M. Sauvageot, N. Albert, J. Alexiev, I. Garcia, F. Struck, D. Van De Vijver, D.A.M.C. Åsjö, B. Beshkov, D. Coughlan, S. Descamps, D. Griskevicius, A. Hamouda, O. Horban, A. Van Kasteren, M. Kolupajeva, T. Kostrikis, L.G. Liitsola, K. Linka, M. Mor, O. Nielsen, C. Otelea, D. Paraskevis, D. Paredes, R. Poljak, M. Puchhammer-Stöckl, E. Sönnerborg, A. Staneková, D. Stanojevic, M. Van Laethem, K. Zazzi, M. Lepej, S.Z. Boucher, C.A.B. Schmit, J.-C. Wensing, A.M.J. 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. Van Wijngaerden, E. Vandercam, B. Vekemans, M. Verhofstede, C. Clumeck, N. Begovac, J. Demetriades, I. Kousiappa, I. Demetriou, V. Hezka, J. Maly, M. Machala, L. Jørgensen, L.B. Gerstoft, J. Mathiesen, L. Pedersen, C. Nielsen, H. Laursen, A. Kvinesdal, B. Ristola, M. Suni, J. Sutinen, J. Assoumou, L. Castor, G. Grude, M. Flandre, P. Storto, A. 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, A. Zavitsanou, A. Vassilakis, A. Lazanas, M. Chini, M. Lioni, A. Sakka, V. Kourkounti, S. Paparizos, V. Antoniadou, A. Papadopoulos, A. Poulakou, G. Katsarolis, I. Protopapas, K. Chryssos, G. Drimis, S. Gargalianos, P. Xylomenos, G. Lourida, G. Psichogiou, M. Daikos, G.L. Sipsas, N.V. Kontos, A. Gamaletsou, M.N. Koratzanis, G. Sambatakou, E. Mariolis, H. Skoutelis, A. Papastamopoulos, V. Georgiou, O. Panagopoulos, P. Maltezos, E. 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. Grossman, Z. De Luca, A. 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. Vasins, O. Lipnickiene, V. Hemmer, R. Arendt, V. Michaux, C. Staub, T. Sequin-Devaux, C. Van Kessel, A. Van Bentum, P.H.M. Brinkman, K. Connell, B.J. Van Der Ende, M.E. Hoepelman, I.M. Kuipers, M. Langebeek, N. Richter, C. Santegoets, R.M.W.J. Schrijnders-Gudde, L. Schuurman, R. Van De Ven, B.J.M. Kran, A.-M.B. Ormaasen, V. Aavitsland, P. Stanczak, J.J. Stanczak, G.P. Firlag-Burkacka, E. Wiercinska-Drapalo, A. Jablonowska, E. Maolepsza, E. Leszczyszyn-Pynka, M. Szata, W. Camacho, R. Palma, C. Borges, F. Paixão, T. Duque, V. Araújo, F. Paraschiv, S. Tudor, A.M. Cernat, R. Chiriac, C. Dumitrescu, F. Prisecariu, L.J. Jevtovic, Dj. Salemovic, D. Stanekova, D. Habekova, M. Chabadová, Z. Drobkova, T. Bukovinova, P. Shunnar, A. Truska, P. Lunar, M. Babic, D. Tomazic, J. Vidmar, L. Vovko, T. Karner, P. Monge, S. Moreno, S. Del Amo, J. Asensi, V. Sirvent, J.L. De Mendoza, C. Delgado, R. Gutiérrez, F. Berenguer, J. Garcia-Bujalance, S. Stella, N. De Los Santos, I. Blanco, J.R. Dalmau, D. Rivero, M. Segura, F. Elías, M.J.P. Alvarez, M. Chueca, N. Rodríguez-Martín, C. Vidal, C. Palomares, J.C. Viciana, I. Viciana, P. Cordoba, J. Aguilera, A. Domingo, P. Galindo, M.J. Miralles, C. Del Pozo, M.A. Ribera, E. Iribarren, J.A. Ruiz, L. De La Torre, J. Vidal, F. Clotet, B. Heidarian, A. Aperia-Peipke, K. Axelsson, M. Mild, M. Karlsson, A. Thalme, A. Navér, L. Bratt, G. Blaxhult, A. Gisslén, M. Svennerholm, B. 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. Bergbrant, I. SPREAD Program

Abstract

Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%-9.5%) in 2008-2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected. © The Author 2015.

Published
2016

12. IMMUNE-ESCAPE MUTATIONS AND STOP-CODONS IN HBSAG CIRCULATES IN A RELEVANT PROPORTION OF PATIENTS WITH CHRONIC HBV INFECTION EXPOSED TO ANTI-HBV DRUGS IN EUROPE: IMPLICATIONS FOR HBV TRANSMISSION IN THE SETTING OF VACCINATION AND DISEASE PROGRESSION

Author

Colagrossi, L. Hermans, L. E. Salpini, R. Pas, S. D. and Alvarez, M. Ben Ari, Z. Boland, G. Bruzzone, B. Coppola, N. Seguin-Devaux, C. Dyda, T. Garcia, F. Kaiser, R. and Kose, S. Krarup, H. Lazarevic, I. Lunar, M. M. Maylin, S. Micheli, V. Mor, O. Paraschiv, S. Paraskevis, D. and Poljak, M. Puchhammer-Stoeckl, E. Simon, F. Stanojevic, M. and Stene-Johansen, K. Tihic, N. Trimoulet, P. Verheyen, J. and Vince, A. Weis, N. Yalcinkaya, T. Lepej, S. Z. and Boucher, C. A. Wensing, A. M. Perno, C. F. Svicher, V. and European Soc Translational

Published
2016

13. Combined analysis of the prevalence of drug-resistant Hepatitis B virus in antiviral therapy-experienced patients in Europe (CAPRE)

Author

Hermans, L.E. Svicher, V. Pas, S.D. Salpini, R. Alvarez, M. Ben Ari, Z. Boland, G. Bruzzone, B. Coppola, N. Seguin-Devaux, C. Dyda, T. Garcia, F. Kaiser, R. Köse, S. Krarup, H. Lazarevic, I. Lunar, M.M. Maylin, S. Micheli, V. Mor, O. Paraschiv, S. Paraskevis, D. Poljak, M. Puchhammer-Stöckl, E. Simon, F. Stanojevic, M. Stene-Johansen, K. Tihic, N. Trimoulet, P. Verheyen, J. Vince, A. Weis, N. Yalcinkaya, T. Lepej, S.Z. Perno, C. Boucher, C.A.B. Wensing, A.M.J.

Abstract

Background European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. Methods A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. Results Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P

Published
2016

14. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe

Author

Moutschen, M., Hofstra, Laura Marije Arije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van, de Vijver, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios N., Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Zidovec Lepej, Snjezana, Boucher, Charles A. B., Schmit, Jean-Claude, Wensing, Annemarie M. J., 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., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van, den Heuvel, Van, Der Gucht, Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Lepej, S. Z., Begovac, J., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Linka, M., Maly, M., Machala, L., 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., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., 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., Zavitsanou, Assimina, Vassilakis, A., Lazanas, Marios C., Chini, Maria C., Lioni, A., Sakka, V., Kourkounti, Sofia, Paparizos, Vassilios A., Antoniadou, Anastasia C., Papadopoulos, Antonios I., Poulakou, Garyphallia G., Katsarolis, I., Protopapas, K., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Xylomenos, Georgios, Lourida, G., Psichogiou, Mina A., Daikos, George L., Sipsas, N. V., Kontos, Athanasios N., Gamaletsou, M. N., Koratzanis, Georgios, Sambatakou, H., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, Periklis, Maltezos, E., 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., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., de Luca, A., Balotta, Claudia, 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., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M. J., Boucher, C. A. B., van, de Vijver, van Kessel, A., van Bentum, P. H. M., Brinkman, K., Connell, B. J., van, der Ende, Hoepelman, I. M., van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., Schuurman, R., van, de Ven, Kran, A. -M B., Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, Ricardo J., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., del Amo, J., Asensi, V., Sirvent, J. L., de Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, Natalia C., de, los Santos, Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elıás, Marıá Jesús Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de, la Torre, Vidal, F., Clotet, B., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, 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., Clinical sciences, Microbiology and Infection Control, Supporting clinical sciences, Clinicum, Department of Medicine, Virology, Cohorte de Adultos de la Red de Investigación en SIDA, Spain., SPREAD Program, [Hofstra,LM, Sauvageot,N, Struck,D, Schmit,JC ] Luxembourg Institute of Health, Luxembourg. [Hofstra,LM, Wensing,AMJ] Department of Virology, University Medical Center Utrecht, The Netherlands. [Albert,J, Sönnerborg,A] Karolinska Institute, Solna. Karolinska University Hospital, Stockholm, Sweden. [Alexiev,I, Beshkov,D] National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria. [Garcia,F] Complejo Hospitalario Universitario de Granada. Instituto de Investigación IBS Granada, Spain. [Van de Vijver,DAMC, Boucher,CAB] Erasmus MC, University Medical Center, Rotterdam, The Netherlands. [Åsjö,B] University of Bergen, Norway. [Coughlan,S] University College Dublin, Ireland. [Descamps,D] AP-HP Groupe hospitalier Bichat-Claude Bernard. IAME INSERM UMR 1137. Université Paris Diderot Sorbonne Paris Cité, Paris, France. [Griskevicius,A] Lithuanian AIDS Center, Vilnius, Lithuania. [Hamouda,O] Robert Koch Institute, Berlin, Germany. [Horban,A] Hospital of Infectious Diseases, Warsaw, Poland. [Van Kasteren,M] St Elisabeth Hospital, Tilburg, The Netherlands. [Kolupajeva,T] Infectiology Center of Latvia, Riga. [Kostrikis,LG] University of Cyprus, Nicosia. [Liitsola,K] Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki, Finland. [Linka,M] National Reference Laboratory for HIV/AIDS, National Institute of Public Health, Prague, Czech Republic. [Mor,O] National HIV Reference Laboratory, Chaim Sheba Medical Center, Tel-Hashomer, Israel. [Nielsen,C] Statens Serum Institut, Copenhagen, Denmark. [Otelea,D] National Institute for Infectious Diseases 'Prof. dr. Matei Bals', Bucharest, Romania. [Paraskevis,D] National Retrovirus Reference Center, University of Athens, Greece. [Paredes,R] IrsiCaixa Foundation, Badalona, Spain. [Poljak,M] Faculty of Medicine, Slovenian HIV/AIDS Reference Centre, University of Ljubljana, Slovenia. [Puchhammer-Stöckl,E] Medical University Vienna, Austria. [Staneková,D] Slovak Medical University, Bratislava, Slovakia. [Stanojevic,M] Faculty of Medicine, University of Belgrade, Serbia. [Van Laethem,K] Rega Institute for Medical Research, KU Leuven, Belgium. [Zazzi,M] University of Siena, Italy. [Zidovec Lepej,S] University Hospital for Infectious Diseases 'Dr. Fran Mihaljevic', Zagreb, Croatia., This work was supported by a CORE grant of Fond National de la Recherche Luxembourg (grant number C12/BM/4011111–HIV molecular epidemiology in Europe). This work has been partially supported by the European Commission (fifth framework, grant number QLK2-CT-2001-01344, sixth framework, grant number LSHP-CT-2006-518211, DynaNets grant number 233847, seventh framework, CHAIN grant number 223131), Belgium: Belgian AIDS Reference Laboratory Fund, Belgian Fonds voor Wetenschappelijk Onderzoek (grant number G.0692.14), Cyprus: Cyprus Research Promotion Foundation (grant number Health/0104/22), Denmark: Danish AIDS Foundation, France: Agence Nationale de Recherches sur le SIDA et les Hepatites Virales, Germany: Ministry of Health (grant number 1502-686-18), Ministry of Education and Research (grant number 01KI501), Italy: Fifth National Program on HIV/AIDS, Instituto Superiore di Sanità (grant numbers 40F.56 and 20D.1.6), Luxembourg: Fondation Recherche sur le SiDA and Ministry of Health, Republic of Serbia: Ministry of Education and Science (grant number 175024), Slovakia: project 'Center of Excellence of Environmental Health,' ITMS number 26240120033, based on supporting operational research and development program financed from the European Regional Development Fund, and Sweden: Swedish Research Council and Swedish Civil Contingencies Agency., APH - Health Behaviors & Chronic Diseases, Graduate School, Hofstra, LM, Sauvageot, N, Albert, J, Alexiev, I, Garcia, F, Struck, D, Van de Vijver, DA, Åsjö, B, Beshkov, D, Coughlan, S, Descamps, D, Griskevicius, A, Hamouda, O, Horban, A, Van Kasteren, M, Kolupajeva, T, Kostrikis, LG, Liitsola, K, Linka, M, Mor, O, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stöckl, E, Sönnerborg, A, Staneková, D, Stanojevic, M, Van Laethem, K, Zazzi, M, Lepej, SZ, Boucher, CA, Schmit, JC, Wensing, AM, SPREAD program investigators, including Vitale F and Tramuto, F, Vandamme, Annemie, Vercauteren, Jurgen, Schrooten, Yoeri, Van Ranst, Marc, Van Wijngaerden, Eric, Derdelinckx, Inge, Camacho, Ricardo Jorge, Kostrikis, Leontios G. [0000-0002-5340-7109], and Paraskevis, Dimitrios [0000-0001-6167-7152]

Subjects
Male, Human immunodeficiency virus 1, Etravirine, RNA directed DNA polymerase inhibitor, darunavir, HIV Infections, Settore MED/42 - Igiene Generale E Applicata, Disciplines and Occupations::Health Occupations::Medicine::Public Health [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Salud pública, genetics, Inhibidores de proteasas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], atazanavir, media_common, transmission, Geographicals::Geographic Locations::Europe [Medical Subject Headings], 3. Good health, microbial sensitivity test, priority journal, Europe, HIV-1, antiretroviral therapy, drug resistance, HIV/AIDS, lamivudine, Reverse Transcriptase Inhibitors/pharmacology, anti human immunodeficiency virus agent, Drug, Microbiology (medical), medicine.medical_specialty, antiviral susceptibility, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], media_common.quotation_subject, 030106 microbiology, HIV Infections/drug therapy, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Reverse Transcriptase Inhibitors [Medical Subject Headings], Microbial Sensitivity Tests, RILPIVIRINE, Article, EFAVIRENZ, 03 medical and health sciences, transmitted drug resistance, SDG 3 - Good Health and Well-being, Humans, Transmission, human, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance [Medical Subject Headings], REVERSE-TRANSCRIPTASE INHIBITORS, Rilpivirina, INTEGRASE, MUTATIONS, abacavir, major clinical study, Virology, Infecciones por VIH, Regimen, Antiretroviral therapy, Drug resistance, Medicine (all), Infectious Diseases, chemistry, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Oxazines::Benzoxazines [Medical Subject Headings], Mutation, 0301 basic medicine, nevirapine, Communicable diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Confidence Intervals [Medical Subject Headings], chemistry.chemical_compound, antiviral therapy, INFECTION, Medicine and Health Sciences, Prevalence, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [Medical Subject Headings], Viral, Non-U.S. Gov't, Reverse-transcriptase inhibitor, antiretrovirus agent, Research Support, Non-U.S. Gov't, Human immunodeficiency virus infected patient, Middle Aged, virology, PREVALENCE, Encuestas y Cuestionarios, ANTIRETROVIRAL TREATMENT, HIV-1/drug effects, HIV Protease Inhibitors/pharmacology, Rilpivirine, Reverse Transcriptase Inhibitors, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Female, HIV drug resistance, medicine.drug, Adult, Human immunodeficiency virus proteinase inhibitor, Chemicals and Drugs::Organic Chemicals::Nitriles::Rilpivirine [Medical Subject Headings], Efavirenz, Anti-HIV Agents, Research Support, Resistencia a medicamentos, Settore MED/17 - MALATTIE INFETTIVE, antiviral resistance, Internal medicine, Anti-HIV Agents/pharmacology, Drug Resistance, Viral, Journal Article, medicine, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings], abacavir plus lamivudine, Europa (Continente), HIV Protease Inhibitors, emtricitabine, nonhuman, Intervalos de confianza, Mutación, business.industry, HIV, prediction, Inhibidores de la transcriptasa inversa, Human immunodeficiency virus 1 infection, tenofovir, INDIVIDUALS, Drug Resistance, Viral/genetics, Benzoxazinas, ETRAVIRINE, drug effects, 3121 General medicine, internal medicine and other clinical medicine, Prevalencia, business
Abstract

Transmitted human immunodeficiency virus drug resistance in Europe is stable at around 8%. The impact of baseline mutation patterns on susceptibility to antiretroviral drugs should be addressed using clinical guidelines. The impact on baseline susceptibility is largest for nonnucleoside reverse transcriptase inhibitors., Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)–infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%–9.5%) in 2008–2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.

Published
2016
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15. RegaDB: Community-driven data management and analysis for infectious diseases

Author

Libin, P, Beheydt, G, Deforche, K, Imbrechts, S, Ferreira, F, Van Laethem, K, Theys, K, Carvalho, A, Cavaco-Silva, J, Lapadula, G, Torti, C, Assel, M, Wesner, S, Snoeck, J, Ruelle, J, De Bel, A, Lacor, P, De Munter, P, Van Wijngaerden, E, Zazzi, M, Kaiser, R, Ayouba, A, Peeters, M, De Oliveira, T, Alcantara, L, Grossman, Z, Sloot, P, Otelea, D, Paraschiv, S, Boucher, C, Camacho, R, Vandamme, A, Libin P., Beheydt G., Deforche K., Imbrechts S., Ferreira F., Van Laethem K., Theys K., Carvalho A. P., Cavaco-Silva J., Lapadula G., Torti C., Assel M., Wesner S., Snoeck J., Ruelle J., De Bel A., Lacor P., De Munter P., Van Wijngaerden E., Zazzi M., Kaiser R., Ayouba A., Peeters M., De Oliveira T., Alcantara L. C. J., Grossman Z., Sloot P., Otelea D., Paraschiv S., Boucher C., Camacho R. J., Vandamme A. -M., Libin, P, Beheydt, G, Deforche, K, Imbrechts, S, Ferreira, F, Van Laethem, K, Theys, K, Carvalho, A, Cavaco-Silva, J, Lapadula, G, Torti, C, Assel, M, Wesner, S, Snoeck, J, Ruelle, J, De Bel, A, Lacor, P, De Munter, P, Van Wijngaerden, E, Zazzi, M, Kaiser, R, Ayouba, A, Peeters, M, De Oliveira, T, Alcantara, L, Grossman, Z, Sloot, P, Otelea, D, Paraschiv, S, Boucher, C, Camacho, R, Vandamme, A, Libin P., Beheydt G., Deforche K., Imbrechts S., Ferreira F., Van Laethem K., Theys K., Carvalho A. P., Cavaco-Silva J., Lapadula G., Torti C., Assel M., Wesner S., Snoeck J., Ruelle J., De Bel A., Lacor P., De Munter P., Van Wijngaerden E., Zazzi M., Kaiser R., Ayouba A., Peeters M., De Oliveira T., Alcantara L. C. J., Grossman Z., Sloot P., Otelea D., Paraschiv S., Boucher C., Camacho R. J., and Vandamme A. -M.

Abstract

RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyse patient data, including viral genetic sequences. Moreover, RegaDB provides researchers with a mechanism to collect data in a uniform format and offers them a canvas to make newly developed bioinformatics tools available to clinicians and virologists through a user friendly interface. © 2013 The Author. Published by Oxford University Press.

Published
2013

16. A21 HIV-1 sub-subtype F1 outbreak among MSM in Belgium

Author

Vinken, L., primary, Fransen, K., additional, Pineda-Peña, A.C., additional, Alexiev, I., additional, Balotta, C., additional, Debaisieux, L., additional, Devaux, C., additional, García Ribas, S., additional, Gomes, P., additional, Incardona, F., additional, Kaiser, R, additional, Ruelle, J., additional, Sayan, M., additional, Paraschiv, S., additional, Paredes, R., additional, Peeters, M., additional, Sonnerborg, A., additional, Vancutsem, E., additional, Van den Wijngaert, S., additional, Van Ranst, M., additional, Verhofstede, C., additional, Vandamme, A.-M., additional, Lemey, P., additional, and Van Laethem, K., additional

Published
2017
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17. 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

18. 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

19. Enhanced HIV-1 surveillance using molecular epidemiology to study and monitor HIV-1 outbreaks among intravenous drug users (IDUs) in Athens and Bucharest

Author

Paraskevis, D. Paraschiv, S. Sypsa, V. Nikolopoulos, G. Tsiara, C. Magiorkinis, G. Psichogiou, M. Flampouris, A. Mardarescu, M. Niculescu, I. Batan, I. Malliori, M. Otelea, D. Hatzakis, A.

Abstract

Background: A significant increase in HIV-1 diagnoses was reported among Injecting Drug Users (IDUs) in the Athens (17-fold) and Bucharest (9-fold) metropolitan areas starting 2011. Methods: Molecular analyses were conducted on HIV-1 sequences from IDUs comprising 51% and 20% of the diagnosed cases among IDUs during 2011-2013 for Greece and Romania, respectively. Phylodynamic analyses were performed using the newly developed birth-death serial skyline model which allows estimating of important epidemiological parameters, as implemented in BEAST programme. Results: Most infections (>90%) occurred within four and three IDU local transmission networks in Athens and Bucharest, respectively. For all Romanian clusters, the viral strains originated from local circulating strains, whereas in Athens, the local strains seeded only two of the four sub-outbreaks. Birth-death skyline plots suggest a more explosive nature for sub-outbreaks in Bucharest than in Athens. In Athens, two sub-outbreaks had been controlled (Re< 1.0) by 2013 and two appeared to be endemic (Re~ 1). In Bucharest one outbreak continued to expand (Re> 1.0) and two had been controlled (Re< 1.0). The lead times were shorter for the outbreak in Athens than in Bucharest. Conclusions: Enhanced molecular surveillance proved useful to gain information about the origin, causal pathways, dispersal patterns and transmission dynamics of the outbreaks that can be useful in a public health setting. © 2015 Elsevier B.V.

Published
2015

20. Recent HIV-1 outbreak among intravenous drug users in Romania: Evidence for cocirculation of CRF14-BG and Subtype F1 Strains

Author

Niculescu, I. Paraschiv, S. Paraskevis, D. Abagiu, A. Batan, I. Banica, L. Otelea, D.

Subjects
mental disorders, virus diseases
Abstract

Since 2011, Romania has faced an HIV outbreak among injecting drug users (IDUs). Our aim was to identify and describe clinical and epidemiological patterns of this outbreak. A cross-sectional study enrolled 138 IDUs diagnosed with HIV infection between 2011 and 2013 with 58 sexually infected individuals included as the control group. The IDUs had a long history of heroin abuse (10 years) and a recent history of new psychostimulant injection (3-4 years). Classical epidemiological data and molecular techniques were used to describe the transmission dynamics. A high prevalence of hepatitis C virus (HCV) coinfection was noted (98.6%) compared to the control group (10.3%) (p

Published
2015

21. Enhanced HIV-1 surveillance using molecular epidemiology to study and monitor HIV-1 outbreaks among intravenous drug users (IDUs) in Athens and Bucharest

Author

Paraskeva, D., Paraschiv, S., Sypsa, V., Nikolopoulos, Georgios K., Tsiara, Chrissa G., Magiorkinis, Gkikas, Psichogiou, M., Flampouris, Andreas, Mardarescu, Mariana, Niculescu, I., Batan, Ionelia, Malliori-Minerva, Melpomeni, Otelea, D., Hatzakis, A., Nikolopoulos, Georgios K.[0000-0002-3307-0246], Magiorkinis, Gkikas [0000-0002-0141-4753], and Psichogiou, M. [0000-0002-3000-8447]

Subjects
Human immunodeficiency virus 1, HIV Infections, Molecular phylogeny, Procedures, Disease Outbreaks, law.invention, Endemic disease, Public health surveillance, law, Hiv infections, Epidemiology, Idus, Public Health Surveillance, Viral, Substance Abuse, Intravenous, Enhanced surveillance hiv-1, Disease outbreaks, Phylogeny, Priority journal, Molecular Epidemiology, Public health, Greece, Virus rna, Sequence analysis, Classification, Health survey, Virus strain, Phylodynamics, Phylogeography, Infectious Diseases, Transmission (mechanics), Molecular epidemiology, RNA, Viral, Intravenous, Human, Microbiology (medical), Substance abuse, medicine.medical_specialty, Epidemic, Major clinical study, Biology, Microbiology, Article, Virus transmission, Acquired immunodeficiency syndrome (AIDS), Virology, medicine, Genetics, Humans, Transmission, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Romania, Hiv-1, Outbreak, Effective reproductive number, medicine.disease, Nonhuman, Human immunodeficiency virus 1 infection, Intravenous drug abuse, Viral phylodynamics, HIV-1, Rna, Demography, Phylogenetic tree
Abstract

A significant increase in HIV-1 diagnoses was reported among Injecting Drug Users (IDUs) in the Athens (17-fold) and Bucharest (9-fold) metropolitan areas starting 2011.Molecular analyses were conducted on HIV-1 sequences from IDUs comprising 51% and 20% of the diagnosed cases among IDUs during 2011-2013 for Greece and Romania, respectively. Phylodynamic analyses were performed using the newly developed birth-death serial skyline model which allows estimating of important epidemiological parameters, as implemented in BEAST programme.Most infections (90%) occurred within four and three IDU local transmission networks in Athens and Bucharest, respectively. For all Romanian clusters, the viral strains originated from local circulating strains, whereas in Athens, the local strains seeded only two of the four sub-outbreaks. Birth-death skyline plots suggest a more explosive nature for sub-outbreaks in Bucharest than in Athens. In Athens, two sub-outbreaks had been controlled (Re1.0) by 2013 and two appeared to be endemic (Re∼1). In Bucharest one outbreak continued to expand (Re1.0) and two had been controlled (Re1.0). The lead times were shorter for the outbreak in Athens than in Bucharest.Enhanced molecular surveillance proved useful to gain information about the origin, causal pathways, dispersal patterns and transmission dynamics of the outbreaks that can be useful in a public health setting.

Published
2015

23. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

Author

Hofstra, L. Marije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van De Vijver, David A M C, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Lepej, Snjezana Zidovec, Boucher, Charles A B, Schmit, Jean Claude, Wensing, Annemarie M J, 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., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Beshkov, D., Alexiev, I., Lepej, S. Zidovec, Begovac, J., Demetriades, I., Kousiappa, I., Demetriou, V., Hezka, J., Linka, M., Maly, M., Machala, L., 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., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., 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., Zavitsanou, A., Vassilakis, A., Lazanas, M., Chini, M., Lioni, A., Sakka, V., Kourkounti, S., Paparizos, V., Antoniadou, A., Papadopoulos, A., Poulakou, G., Katsarolis, I., Protopapas, K., Chryssos, G., Drimis, S., Gargalianos, P., Xylomenos, G., Lourida, G., Psichogiou, M., Daikos, G. L., Sipsas, N. V., Kontos, A., Gamaletsou, M. N., Koratzanis, G., Sambatakou, E., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, P., Maltezos, E., 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., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., De Luca, A., 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., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Sauvageot, N., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M J, Boucher, C. A B, Van Kessel, A., Van Bentum, P. H M, Brinkman, K., Connell, B. J., Van Der Ende, M. E., Hoepelman, I. M., Van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M W J, Schrijnders-Gudde, L., Schuurman, R., Van De Ven, B. J M, Åsjö, B., Kran, A. M Bakken, Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, R., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, D., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., Del Amo, J., Asensi, V., Sirvent, J. L., De Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, N., De Los Santos, I., Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elías, M. J Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., Del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., De La Torre, J., Vidal, F., Clotet, B., Albert, J., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, P., Säll, C., Mellgren, 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., Hofstra, L. Marije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van De Vijver, David A M C, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Lepej, Snjezana Zidovec, Boucher, Charles A B, Schmit, Jean Claude, Wensing, Annemarie M J, 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., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Beshkov, D., Alexiev, I., Lepej, S. Zidovec, Begovac, J., Demetriades, I., Kousiappa, I., Demetriou, V., Hezka, J., Linka, M., Maly, M., Machala, L., 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., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., 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., Zavitsanou, A., Vassilakis, A., Lazanas, M., Chini, M., Lioni, A., Sakka, V., Kourkounti, S., Paparizos, V., Antoniadou, A., Papadopoulos, A., Poulakou, G., Katsarolis, I., Protopapas, K., Chryssos, G., Drimis, S., Gargalianos, P., Xylomenos, G., Lourida, G., Psichogiou, M., Daikos, G. L., Sipsas, N. V., Kontos, A., Gamaletsou, M. N., Koratzanis, G., Sambatakou, E., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, P., Maltezos, E., 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., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., De Luca, A., 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., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Sauvageot, N., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M J, Boucher, C. A B, Van Kessel, A., Van Bentum, P. H M, Brinkman, K., Connell, B. J., Van Der Ende, M. E., Hoepelman, I. M., Van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M W J, Schrijnders-Gudde, L., Schuurman, R., Van De Ven, B. J M, Åsjö, B., Kran, A. M Bakken, Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, R., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, D., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., Del Amo, J., Asensi, V., Sirvent, J. L., De Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, N., De Los Santos, I., Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elías, M. J Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., Del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., De La Torre, J., Vidal, F., Clotet, B., Albert, J., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, P., Säll, C., Mellgren, 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., and Ryding, U.

Published
2016

24. IMMUNE-ESCAPE MUTATIONS AND STOP-CODONS IN HBSAG CIRCULATES IN A RELEVANT PROPORTION OF PATIENTS WITH CHRONIC HBV INFECTION EXPOSED TO ANTI-HBV DRUGS IN EUROPE: IMPLICATIONS FOR HBV TRANSMISSION IN THE SETTING OF VACCINATION AND DISEASE PROGRESSION

Author

Colagrossi, L., Hermans, L. E., Salpini, R., Pas, S. D., Alvarez, M., Ben Ari, Z., Boland, G., Bruzzone, B., Coppola, N., Seguin-Devaux, C., Dyda, T., Garcia, F., Kaiser, R., Kose, S., Krarup, H., Lazarevic, I., Lunar, M. M., Maylin, S., Micheli, V., Mor, O., Paraschiv, S., Paraskevis, D., Poljak, M., Puchhammer-Stoeckl, E., Simon, F., Stanojevic, M., Stene-Johansen, K., Tihic, N., Trimoulet, P., Verheyen, J., Vince, A., Weis, N., Yalcinkaya, T., Lepej, S. Z., Boucher, C. A., Wensing, A. M., Perno, C. F., Svicher, V., Colagrossi, L., Hermans, L. E., Salpini, R., Pas, S. D., Alvarez, M., Ben Ari, Z., Boland, G., Bruzzone, B., Coppola, N., Seguin-Devaux, C., Dyda, T., Garcia, F., Kaiser, R., Kose, S., Krarup, H., Lazarevic, I., Lunar, M. M., Maylin, S., Micheli, V., Mor, O., Paraschiv, S., Paraskevis, D., Poljak, M., Puchhammer-Stoeckl, E., Simon, F., Stanojevic, M., Stene-Johansen, K., Tihic, N., Trimoulet, P., Verheyen, J., Vince, A., Weis, N., Yalcinkaya, T., Lepej, S. Z., Boucher, C. A., Wensing, A. M., Perno, C. F., and Svicher, V.

Published
2016

25. Transmission of HIV drug resistance and the predicted effect on current first-line regimens in Europe

Author

MMB opleiding Arts microbioloog, MMB Medische Staf, Infection & Immunity, Onderzoek Bob Oranje, Brain, Cardiovasculaire Epi Team 1, MMB Research line 3a, MS Infectieziekten, Circulatory Health, MMB Staf diagnostiek, Hofstra, L. Marije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van De Vijver, David A M C, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Lepej, Snjezana Zidovec, Boucher, Charles A B, Schmit, Jean Claude, Wensing, Annemarie M J, 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., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Beshkov, D., Alexiev, I., Lepej, S. Zidovec, Begovac, J., Demetriades, I., Kousiappa, I., Demetriou, V., Hezka, J., Linka, M., Maly, M., Machala, L., 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., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., 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., Zavitsanou, A., Vassilakis, A., Lazanas, M., Chini, M., Lioni, A., Sakka, V., Kourkounti, S., Paparizos, V., Antoniadou, A., Papadopoulos, A., Poulakou, G., Katsarolis, I., Protopapas, K., Chryssos, G., Drimis, S., Gargalianos, P., Xylomenos, G., Lourida, G., Psichogiou, M., Daikos, G. L., Sipsas, N. V., Kontos, A., Gamaletsou, M. N., Koratzanis, G., Sambatakou, E., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, P., Maltezos, E., 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., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., De Luca, A., 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., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Sauvageot, N., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M J, Boucher, C. A B, Van Kessel, A., Van Bentum, P. H M, Brinkman, K., Connell, B. J., Van Der Ende, M. E., Hoepelman, I. M., Van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M W J, Schrijnders-Gudde, L., Schuurman, R., Van De Ven, B. J M, Åsjö, B., Kran, A. M Bakken, Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, R., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, D., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., Del Amo, J., Asensi, V., Sirvent, J. L., De Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, N., De Los Santos, I., Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elías, M. J Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., Del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., De La Torre, J., Vidal, F., Clotet, B., Albert, J., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, P., Säll, C., Mellgren, 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., MMB opleiding Arts microbioloog, MMB Medische Staf, Infection & Immunity, Onderzoek Bob Oranje, Brain, Cardiovasculaire Epi Team 1, MMB Research line 3a, MS Infectieziekten, Circulatory Health, MMB Staf diagnostiek, Hofstra, L. Marije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van De Vijver, David A M C, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios, Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Lepej, Snjezana Zidovec, Boucher, Charles A B, Schmit, Jean Claude, Wensing, Annemarie M J, 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., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Beshkov, D., Alexiev, I., Lepej, S. Zidovec, Begovac, J., Demetriades, I., Kousiappa, I., Demetriou, V., Hezka, J., Linka, M., Maly, M., Machala, L., 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., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., 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., Zavitsanou, A., Vassilakis, A., Lazanas, M., Chini, M., Lioni, A., Sakka, V., Kourkounti, S., Paparizos, V., Antoniadou, A., Papadopoulos, A., Poulakou, G., Katsarolis, I., Protopapas, K., Chryssos, G., Drimis, S., Gargalianos, P., Xylomenos, G., Lourida, G., Psichogiou, M., Daikos, G. L., Sipsas, N. V., Kontos, A., Gamaletsou, M. N., Koratzanis, G., Sambatakou, E., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, P., Maltezos, E., 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., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., De Luca, A., 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., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Sauvageot, N., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M J, Boucher, C. A B, Van Kessel, A., Van Bentum, P. H M, Brinkman, K., Connell, B. J., Van Der Ende, M. E., Hoepelman, I. M., Van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M W J, Schrijnders-Gudde, L., Schuurman, R., Van De Ven, B. J M, Åsjö, B., Kran, A. M Bakken, Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, R., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, D., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., Del Amo, J., Asensi, V., Sirvent, J. L., De Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, N., De Los Santos, I., Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elías, M. J Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., Del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., De La Torre, J., Vidal, F., Clotet, B., Albert, J., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, P., Säll, C., Mellgren, 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., and Ryding, U.

Published
2016

26. Immune-Escape Mutations and Stop-Codons in HBsAg Circulates in a Relevant Proportion of Patients with Chronic HBV Infection Exposed to Anti-HBV Drugs in Europe: Implications for HBV Transmission in the Setting of Vaccination and Disease Progression

Author

Colagrossi, L., primary, Hermans, L.E., additional, Salpini, R., additional, Pas, S.D., additional, Alvarez, M., additional, Ben Ari, Z., additional, Boland, G., additional, Bruzzone, B., additional, Coppola, N., additional, Seguin-Devaux, C., additional, Dyda, T., additional, Garcia, F., additional, Kaiser, R., additional, Köse, S., additional, Krarup, H., additional, Lazarevic, I., additional, Lunar, M.M., additional, Maylin, S., additional, Micheli, V., additional, Mor, O., additional, Paraschiv, S., additional, Paraskevis, D., additional, Poljak, M., additional, Puchhammer-Stöckl, E., additional, Simon, F., additional, Stanojevic, M., additional, Stene-Johansen, K., additional, Tihic, N., additional, Trimoulet, P., additional, Verheyen, J., additional, Vince, A., additional, Weis, N., additional, Yalcinkaya, T., additional, Lepej, S.Z., additional, Boucher, C.A., additional, Wensing, A.M., additional, Perno, C.F., additional, and Svicher, V., additional

Published
2016
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27. Molecular typing of the recently expanding subtype B HIV-1 epidemic in Romania: Evidence for local spread among MSMs in Bucharest area

Author

Paraschiv, S. Otelea, D. Batan, I. Baicus, C. Magiorkinis, G. Paraskevis, D.

Abstract

HIV-1 subtype B is predominant in Europe except in some countries from Eastern Europe which are characterized by a high prevalence of non-B subtypes and circulating recombinant forms (CRFs). Romania is a particular case: the HIV-1 epidemic started with subtype F1 which is still the most prevalent. Previous studies have shown an increasing prevalence of subtype B which is the second most frequent one among the newly diagnosed individuals, followed by subtype C and several CRFs as well as unique recombinant forms (URFs). Our objective was to analyze in detail the characteristics (way of dispersal, association with transmission risk groups) of the subtype B infections in Romania by means of phylogenetic analysis. Among all the individuals sampled during 2003-2010, 71 out of 1127 patients (6.3%) have been identified to be infected with subtype B strains. The most frequent route of infection identified in HIV-1 subtype B patients in Romania was MSM transmission (39.6%), followed by the heterosexual route (35.2%). Many of the patients acquired the infection abroad, mainly in Western European countries. Phylogenetic analysis indicated the existence of a local transmission network (monophyletic clade) including 14 patients, mainly MSM living in the Bucharest area. We estimate the origin of the local transmission network that dates at the beginning of the 90s; the introduction of the F1 and C subtypes occurred earlier. The rest of the sequences were intermixed with reference strains sampled across Europe suggesting that single infection were not followed by subsequent dispersal within the local population. Although HIV-1 subtype B epidemic in Romania is recent, there is evidence for local spread among the MSMs, in addition to multiple introductions. © 2012 Elsevier B.V.

Published
2012

28. HIV-1 molecular epidemiology in the Balkans - A melting pot for high genetic diversity

Author

Stanojevic M, Alexiev I, Beshkov D, Gökengin D, Mezei M, Minarovits J, Dan Otelea, Paraschiv S, Poljak M, Zidovec-Lepej S, and Paraskevis D

Subjects
HIV-1, Balkan, epidemiology
Abstract

The Balkans is a gateway between Europe, Asia, and the African continent, a fact with potential important consequences on the epidemiology of HIV‑1 infection in the region. The duration of the HIV‑1 epidemics in many countries of the Balkans is similar to the one in the Western European countries. However, striking differences exist in several countries of the region in both the epidemic situation and, even more so, in our knowledge about it. In particular, the molecular epidemiology of HIV in the Balkans is largely unknown. In order to gain some preliminary insight into HIV‑1 diversity in the region, we reviewed the available molecular epidemiology data about HIV‑1 diversity in 10 countries of the region: Albania, Bulgaria, Croatia, Greece, Montenegro, Romania, Slovenia, Serbia, Turkey, and Hungary, a neighboring country to four Balkan countries. The data were obtained either from published studies or in direct communication with the participating members. The existing molecular epidemiology data revealed a broad diversity in subtype distribution among Balkan countries. In several countries, subtype B is predominant (e.g. Serbia, Slovenia, and Hungary), while in others the proportion of non‑B subtypes is much larger (Albania subtype A, Romania subtype F). In some areas, HIV‑1 subtype distribution is marked by divergence between different risk groups or transmission routes (e.g. Croatia). Recently, HIV‑1/AIDS epidemics in Eastern Europe have been among the fastest growing in the world. Many major contributing factors for the breakout and spread of these epidemics are present in many of the Balkan countries, as reflected through the process of social transition, wars, unemployment, extensive drug use, high sexual risk behavior, as well as other factors. Yet, in the Balkan countries the prevalence rate of HIV‑1 infection is low, under 0.1 percent. Concomitantly, the molecular epidemiology of HIV‑1 in the Balkans has not been thoroughly studied so far. The review and analysis of the available data indicate a broad diversity of circulating HIV‑1 subtypes in the region, with the predominance of non‑B clades in some countries, underscoring the need for an ongoing surveillance of HIV‑1 diversity. The setup of a collaborative network might provide important information for the better management and control of the HIV‑1 epidemic in the area.

Published
2012

29. THU-136 - Immune-Escape Mutations and Stop-Codons in HBsAg Circulates in a Relevant Proportion of Patients with Chronic HBV Infection Exposed to Anti-HBV Drugs in Europe: Implications for HBV Transmission in the Setting of Vaccination and Disease Progression

Author

Colagrossi, L., Hermans, L.E., Salpini, R., Pas, S.D., Alvarez, M., Ben Ari, Z., Boland, G., Bruzzone, B., Coppola, N., Seguin-Devaux, C., Dyda, T., Garcia, F., Kaiser, R., Köse, S., Krarup, H., Lazarevic, I., Lunar, M.M., Maylin, S., Micheli, V., Mor, O., Paraschiv, S., Paraskevis, D., Poljak, M., Puchhammer-Stöckl, E., Simon, F., Stanojevic, M., Stene-Johansen, K., Tihic, N., Trimoulet, P., Verheyen, J., Vince, A., Weis, N., Yalcinkaya, T., Lepej, S.Z., Boucher, C.A., Wensing, A.M., Perno, C.F., and Svicher, V.

Published
2016
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30. Impact of highly active antiretroviral therapy on cytomegalovirus viraemia, in the absence of specific anti-cytomegalovirus therapy

Author

Mihailescu, R, primary, Paraschiv, S, additional, Arama, V, additional, Streinu-Cercel, A, additional, Otelea, D, additional, Benea, OE, additional, Iosipenco, M, additional, Mardarescu, M, additional, Luminos, M, additional, Munteanu, D, additional, Radulescu, M, additional, Chiotan, C, additional, Hristea, A, additional, and Ungurianu, R, additional

Published
2008
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36. Detection of Mycobacterium tuberculosisresistance mutations to rifampin and isoniazid by real-time PCR

Author

Hristea, A, Otelea, D, Paraschiv, S, Macri, A, Baicus, C, Moldovan, O, Tinischi, M, Arama, V, and Streinu-Cercel, A

Abstract

Objective:The objective of our study was to evaluate the use of a real-time polymerase chain reaction (PCR)-based technique for the prediction of phenotypic resistance of Mycobacterium tuberculosis. Materials and Methods:We tested 67 M tuberculosisstrains (26 drug resistant and 41 drug susceptible) using a method recommended for the LightCycler platform. The susceptibility testing was performed by the absolute concentration method. For rifampin resistance, two regions of the rpoBgene were targeted, while for identification of isoniazid resistance, we searched for mutations in katGand inhAgenes. Results:The sensitivity and specificity of this method for rapid detection of mutations for isoniazid resistance were 96% (95% CI: 88% to 100%) and 95% (95% CI: 89% to 100%), respectively. For detection of rifampin resistance, the sensitivity and specificity were 92% (95% CI: 81% to 100%) and 74% (95% CI: 61% to 87%), respectively. The main isoniazid resistance mechanism identified in our isolates is related to changes in the katGgene that encodes catalase. We found that for rifampin resistance the concordance between the predicted and observed phenotype was less than satisfactory. Conclusions:Using this method, the best accuracy for genotyping compared with phenotypic resistance testing was obtained for detecting isoniazid resistance mutations. Although real-time PCR assay may be a valuable diagnostic tool, it is not yet completely satisfactory for detection of drug resistance mutations in M tuberculosis.

Published
2010
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43. Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

Author

Tülay Yalcinkaya, Pascale Trimoulet, Valeria Micheli, Adriana Vince, G. J. Boland, Maja M. Lunar, Jens Verheyen, Carlo Federico Perno, Bianca Bruzzone, Charles A. Boucher, Henrik Krarup, Sarah Maylin, Sukran Kose, Nicola Coppola, Kathrine Stene-Johansen, Annemarie M. J. Wensing, Rolf Kaiser, François Simon, Maja Stanojevic, Lucas Etienne Hermans, Mario Poljak, Simona Paraschiv, Nijaz Tihic, Valentina Svicher, L. Colagrossi, Ziv Ben-Ari, Tomasz Dyda, Federico García, Orna Mor, Ivana Lazarevic, Marta Álvarez, Nina Weis, Suzan D. Pas, Snjezana Zidovec Lepej, Carole Seguin-Devaux, Elisabeth Puchhammer-Stöckl, Domenico Di Carlo, Romina Salpini, Dimitros Paraskevis, Virology, Colagrossi, L, Hermans, Le, Salpini, R, Di Carlo, D, Pas, Sd, Alvarez, M, Ben-Ari, Z, Boland, G, Bruzzone, B, Coppola, N, Seguin-Devaux, C, Dyda, T, Garcia, F, Kaiser, R, Köse, S, Krarup, H, Lazarevic, I, Lunar, Mm, Maylin, S, Micheli, V, Mor, O, Paraschiv, S, Paraskevis, D, Poljak, M, Puchhammer-Stöckl, E, Simon, F, Stanojevic, M, Stene-Johansen, K, Tihic, N, Trimoulet, P, Verheyen, J, Vince, A, Lepej, Sz, Weis, N, Yalcinkaya, T, Boucher, Cab, Wensing, Amj, Perno, Cf, and Svicher, V

Subjects
Adult, Male, 0301 basic medicine, Immune-escape, Hepatitis B virus, medicine.medical_specialty, HBsAg, Genotype, Medizin, Drug resistance, medicine.disease_cause, Antiviral Agents, Virus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Hepatitis B, Chronic, 0302 clinical medicine, Medical microbiology, medicine, HBV, Humans, Stop-codons, lcsh:RC109-216, Drug-resistance, Mutation, Hepatitis B Surface Antigens, business.industry, Middle Aged, Settore MED/07 - Microbiologia e Microbiologia Clinica, Virology, Stop codon, 3. Good health, Europe, 030104 developmental biology, Infectious Diseases, Amino Acid Substitution, Parasitology, Codon, Terminator, Female, 030211 gastroenterology & hepatology, business, Research Article
Abstract

Background HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. Methods This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. Results At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32–3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P

Published
2018
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44. RegaDB: community-driven data management and analysis for infectious diseases

Author

Dan Otelea, Eric Van Wijngaerden, Paul De Munter, Martine Peeters, Anne-Mieke Vandamme, Pieter Libin, Joke Snoeck, Stijn Imbrechts, Zehava Grossman, Stefan Wesner, Koen Deforche, Annelies De Bel, Luiz Carlos Junior Alcantara, Jean Ruelle, Ahidjo Ayouba, Simona Paraschiv, Matthias Assel, Kristof Theys, Fossie Ferreira, Gertjan Beheydt, Rolf Kaiser, Carlo Torti, Patrick Lacor, Ricardo Jorge Camacho, Maurizio Zazzi, Joana Cavaco-Silva, Kristel Van Laethem, Tulio de Oliveira, Charles A. Boucher, Giuseppe Lapadula, Peter M. A. Sloot, Ana Patricia Carvalho, Computational Science Lab (IVI, FNWI), Centro de Malária e outras Doenças Tropicais (CMDT), Libin, P, Beheydt, G, Deforche, K, Imbrechts, S, Ferreira, F, Van Laethem, K, Theys, K, Carvalho, A, Cavaco-Silva, J, Lapadula, G, Torti, C, Assel, M, Wesner, S, Snoeck, J, Ruelle, J, De Bel, A, Lacor, P, De Munter, P, Van Wijngaerden, E, Zazzi, M, Kaiser, R, Ayouba, A, Peeters, M, De Oliveira, T, Alcantara, L, Grossman, Z, Sloot, P, Otelea, D, Paraschiv, S, Boucher, C, Camacho, R, Vandamme, A, School of Computer Engineering, Cell biology, and Virology

Subjects
Statistics and Probability, Source code, Databases, Factual, Database Management Systems, Humans, Software, Virus Diseases, Computer science, Interface (Java), Data management, media_common.quotation_subject, Databases and Ontologies, Biochemistry, World Wide Web, Databases, 03 medical and health sciences, Documentation, SDG 3 - Good Health and Well-being, Database Management System, Molecular Biology, Factual, 030304 developmental biology, media_common, 0303 health sciences, 030306 microbiology, business.industry, Engineering::Computer science and engineering::Computer applications::Life and medical sciences [DRNTU], Applications Notes, Data science, 3. Good health, Computer Science Applications, Computational Mathematics, Computational Theory and Mathematics, business, Human
Abstract

Summary: RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyze patient data, including viral genetic sequences. Moreover, RegaDB provides researchers with a mechanism to collect data in a uniform format and offers them a canvas to make newly developed bioinformatics tools available to clinicians and virologists through a user friendly interface. Availability and implementation: Source code, binaries and documentation are available on http://regaweb.med.kuleuven.be/software/regadb/ RegaDB is written in the Java programming language, using a web-service oriented architecture. Contact: pieter.libin@rega.kuleuven.be Supplementary information: Supplementary material demonstrating the functionalities of the system is available at Bioinformatics online. Published version

Published
2013
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45. Age, comorbidity burden and late presentation are significant predictors of hospitalization length and acute respiratory failure in patients with influenza.

Author

Miron VD, Săndulescu O, Streinu-Cercel A, Florea D, Paraschiv S, Bănică L, Vlaicu O, Oțelea D, Bilașco A, Pițigoi D, Streinu-Cercel A, and Drăgănescu AC

Subjects
Humans, Male, Female, Middle Aged, Aged, Adolescent, Adult, Child, Child, Preschool, Infant, Young Adult, Prospective Studies, Age Factors, Acute Disease, Aged, 80 and over, Risk Factors, Influenza, Human epidemiology, Influenza, Human complications, Hospitalization statistics & numerical data, Comorbidity, Length of Stay, Respiratory Insufficiency epidemiology
Abstract

Influenza viruses are responsible for a high number of infections and hospitalizations every year. In this study, we aimed to identify clinical and host-specific factors that influence the duration of hospitalization and the progression to acute respiratory failure (ARF) in influenza. We performed an analysis of data from a prospective active influenza surveillance study that was conducted over five seasons (2018/19 to 2022/23). A total of 1402 patients with influenza were included in the analysis, the majority of which (64.5%) were children (under 18 years), and 9.1% were elderly. At least one chronic condition was present in 29.2% of patients, and 9.9% of patients developed ARF. The median hospital stay was 4 days (IQR: 3, 6 days). The most important predictors of prolonged hospital stay and development of ARF were extremes of age (infants and elderly), presence of chronic diseases, particularly the cumulus of at least 3 chronic diseases, and late presentation to hospital. Among the chronic diseases, chronic obstructive pulmonary disease, cardiovascular disease, cancer, diabetes, obesity, and chronic kidney disease were strongly associated with a longer duration of hospitalization and occurrence of ARF. In this context, interventions aimed at chronic disease management, promoting influenza vaccination, and improving awareness and access to health services may contribute to reducing the impact of influenza not only in Romania but globally. In addition, continued monitoring of the circulation of influenza viruses is essential to limit their spread among vulnerable populations., (© 2024. The Author(s).)

Published
2024
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46. Clinical, epidemiological and molecular aspects of patients with mpox in Romania.

Author

Hohan R, Vlaicu O, Bănică L, Tudor AI, Negru A, Paraschiv S, and Oţelea D

Abstract

Introduction: To better understand the factors which influence the spread of monkeypox (mpox) infection, the patients that tested positive for mpox virus by real-time PCR in one of the main infectious diseases centers in Bucharest were analyzed in this study, amounting to one third of the confirmed cases in Romania., Methods: Clinical data and laboratory tests were used to build the patient profiles. In the case of positive mpox results, next-generation sequencing of the viral genome was also performed to better comprehend the epidemiology of the infections and the evolutionary path of this virus., Results: Among 47 patients with clinical suspicion of infection, 18 cases tested positive for mpox by real-time PCR (RT-PCR). Patients were mainly men who have sex with men (MSM), often coinfected with HIV-1 (half of the cases) and presenting with other sexually transmitted infections (STIs). Phylogenetic analysis was performed on 20 samples (15 patients) and indicated that mpox cases in Romania were the result of multiple importing events followed by local spread. A few sequences from European countries (Germany, Italy, France) and USA were found to be closely related to the Romanian sequences. Intra-host evolution was observed and documented in one patient with HIV-1 infection with uncontrolled viremia, showing slightly different mutation profiles in two body compartments., Conclusions: This study showed that the mpox cases from Romania presented similar clinical, epidemiological and mutational features with those reported by other European countries., Competing Interests: Conflicts of interest: All authors – none to declare., (GERMS.)

Published
2024
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47. Decoding the resistome, virulome and mobilome of clinical versus aquatic Acinetobacter baumannii in southern Romania.

Author

Gheorghe-Barbu I, Surleac M, Barbu IC, Paraschiv S, Bănică LM, Rotaru LI, Vrâncianu CO, Niță Lazăr M, Oțelea D, and Chifiriuc MC

Abstract

Acinetobacter baumannii , a notorious opportunistic pathogen, presents a formidable challenge in both clinical and environmental fields due to its resilience and ability to acquire resistance. This study undertook a comprehensive analysis of 183 A. baumannii isolates collected between 2019 and 2022 from intra-hospital infections (IHI), hospital sewages (Hs), wastewater treatment plants (WWTP), and adjacent river waters from two Southern cities, focusing on their resistome, virulome, and mobilome through isolation on chromogenic media, identification by MALDI-TOF-MS and antibiotic susceptibility testing by disk diffusion) followed by genotypic characterization [Whole Genome Sequencing (WGS), 3rd generation sequencing through the MinION (ONT) platform, pangenome description, and respectively horizontal gene transfer through conjugation assays]. Our findings reveal significant genomic plasticity and the prevalence of high-risk international clones, underlining the potential of these isolates to act as reservoirs for antibiotic resistance genes (ARGs) that could be dynamically exchanged between clinical and environmental settings through mobile genetic elements (MGEs) such as the pMAL1 plasmids and the critical role of WWTPs in the persistence and spread of A. baumannii . Moreover, our study presents the first report of the co-occurrence of bla OXA-23 and bla OXA-72 in A. baumannii ST2 clone. Thus, our research underscores the necessity for integrated surveillance and targeted interventions across healthcare and environmental sectors to mitigate the risk posed by this adaptable pathogen., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Published
2024
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48. First report of Candida auris in Romania: clinical and molecular aspects.

Author

Stanciu AM, Florea D, Surleac M, Paraschiv S, Oțelea D, Tălăpan D, and Popescu GA

Subjects
Humans, Romania epidemiology, Antifungal Agents pharmacology, Disease Outbreaks, Candida auris, Candida genetics
Abstract

The emerging opportunistic fungal pathogen Candida auris raises significant concerns for public health due to its outbreak potential, the associated high mortality, increased resistance to antifungals, challenging identification to species level, since commonly used diagnostic methods can confuse this fungus with other Candida spp. The present outbreak report describes probably some of the first Candida auris cases in Romania, providing clinical and epidemiological data, and also whole genome sequencing data. The cases were identified in three hospitals in Bucharest during the first eight months of 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Published
2023
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49. HIV-1 subtype B spread through cross-border clusters in the Balkans: a molecular analysis in view of incidence trends.

Author

Jovanovic L, Siljic M, Cirkovic V, Salemovic D, Jevtovic D, Alexiev I, Zidovec-Lepej S, Oroz M, Begovac J, Paraskevis D, Skoura L, Chaztidimitriou D, Kostaki EG, Dragas S, Dupanovic B, Otelea D, Paraschiv S, Poljak M, Lunar MM, and Stanojevic M

Subjects
Humans, Male, Bayes Theorem, Homosexuality, Male, Phylogeny, Retrospective Studies, HIV-1 genetics, Sexual and Gender Minorities, HIV Infections epidemiology
Abstract

Objectives: To analyze phylogenetic relations and assess the role of cross-border clusters in the spread of HIV-1 subtype B across the Balkans, given the general trends of new HIV diagnoses in seven Balkan countries., Design: Retrospective phylogenetic and trend analysis., Methods: In-depth phylogenetic, phylodynamic and phylogeographic analysis performed on 2415 HIV-1 subtype B sequences from 1999 to 2019 using maximal likelihood and Bayesian methods. The joinpoint regression analysis of new HIV diagnoses by country and modes of transmission using 2004-2019 ECDC data., Results: Ninety-three HIV-1 Subtype B transmission clusters (68% of studied sequences) were detected of which four cross-border clusters (11% of studied sequences). Phylodynamic analysis showed activity of cross-border clusters up until the mid-2000s, with a subsequent stationary growth phase. Phylogeography analyses revealed reciprocal spread patterns between Serbia, Slovenia and Montenegro and several introductions to Romania from these countries and Croatia. The joinpoint analysis revealed a reduction in new HIV diagnoses in Romania, Greece and Slovenia, whereas an increase in Serbia, Bulgaria, Croatia and Montenegro, predominantly among MSM., Conclusion: Differing trends of new HIV diagnoses in the Balkans mirror differences in preventive policies implemented in participating countries. Regional spread of HIV within the countries of former Yugoslavia has continued to play an important role even after country break-up, whereas the spread of subtype B through multiple introductions to Romania suggested the changing pattern of travel and migration linked to European integration of Balkan countries in the early 2000s., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2023
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50. Temporo-spatial variations in resistance determinants and clonality of Acinetobacter baumannii and Pseudomonas aeruginosa strains from Romanian hospitals and wastewaters.

Author

Gheorghe-Barbu I, Barbu IC, Popa LI, Pîrcălăbioru GG, Popa M, Măruțescu L, Niță-Lazar M, Banciu A, Stoica C, Gheorghe Ș, Lucaciu I, Săndulescu O, Paraschiv S, Surleac M, Talapan D, Muntean AA, Preda M, Muntean MM, Dragomirescu CC, Popa MI, Oțelea D, and Chifiriuc MC

Subjects
Anti-Bacterial Agents pharmacology, Drug Resistance, Multiple, Bacterial genetics, Hospitals, Interleukin-1 Receptor-Like 1 Protein, Microbial Sensitivity Tests, Pseudomonas aeruginosa genetics, Romania epidemiology, Wastewater microbiology, Wastewater-Based Epidemiological Monitoring, beta-Lactamases genetics, Acinetobacter baumannii
Abstract

Background: Romania is one of the European countries reporting very high antimicrobial resistance (AMR) rates and consumption of antimicrobials. We aimed to characterize the AMR profiles and clonality of 304 multi-drug resistant (MDR) Acinetobacter baumannii (Ab) and Pseudomonas aeruginosa (Pa) strains isolated during two consecutive years (2018 and 2019) from hospital settings, hospital collecting sewage tanks and the receiving wastewater treatment plants (WWTPs) located in the main geographical regions of Romania., Methods: The strains were isolated on chromogenic media and identified by MALDI-TOF-MS. Antibiotic susceptibility testing and confirmation of ESBL- and CP- producing phenotypes and genotypes were performed. The genetic characterization also included horizontal gene transfer experiments, whole-genome sequencing (WGS), assembling, annotation and characterization., Results: Both clinical and aquatic isolates exhibited high MDR rates, especially the Ab strains isolated from nosocomial infections and hospital effluents. The phenotypic resistance profiles and MDR rates have largely varied by sampling point and geographic location. The highest MDR rates in the aquatic isolates were recorded in Galați WWTP, followed by Bucharest. The Ab strains harbored mostly bla OXA-23 , bla OXA-24 , bla SHV , bla TEM and bla GES , while Pa strains bla IMP , bla VIM , bla NDM , bla VEB , bla GES and bla TEM , with high variations depending on the geographical zone and the sampling point. The WGS analysis revealed the presence of antibiotic resistance genes (ARGs) to other antibiotic classes, such as aminoglycosides, tetracyclines, sulphonamides, fosfomycin, phenicols, trimethoprim-sulfamethoxazole as well as class 1 integrons. The molecular analyses highlighted: (i) The presence of epidemic clones such as ST2 for Ab and ST233 and ST357 for Pa; (ii) The relatedness between clinical and hospital wastewater strains and (iii) The possible dissemination of clinical Ab belonging to ST2 (also proved in the conjugation assays for bla OXA-23 or bla OXA-72 genes), ST79 and ST492 and of Pa strains belonging to ST357, ST640 and ST621 in the wastewaters., Conclusion: Our study reveals the presence of CP-producing Ab and Pa in all sampling points and the clonal dissemination of clinical Ab ST2 strains in the wastewaters. The prevalent clones were correlated with the presence of class 1 integrons, suggesting that these isolates could be a significant reservoir of ARGs, being able to persist in the environment., (© 2022. The Author(s).)

Published
2022
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