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1. Dating the Origin and Estimating the Transmission Rates of the Major HIV‐1 Clusters in Greece: Evidence about the Earliest Subtype A1 Epidemic in Europe

Author

Limnaios, S. Kostaki, E.G. Adamis, G. Astriti, M. Chini, M. Mangafas, N. Lazanas, M. Patrinos, S. Metallidis, S. Tsachouridou, O. Papastamopoulos, V. Kakalou, E. Chatzidimitriou, D. Antoniadou, A. Papadopoulos, A. Psichogiou, M. Basoulis, D. Gova, M. Pilalas, D. Paraskeva, D. Chrysos, G. Paparizos, V. Kourkounti, S. Sambatakou, H. Bolanos, V. Sipsas, N.V. Lada, M. Barbounakis, E. Kantzilaki, E. Panagopoulos, P. Maltezos, E. Drimis, S. Sypsa, V. Lagiou, P. Magiorkinis, G. Hatzakis, A. Skoura, L. Paraskevis, D.

Abstract

Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infec-tions/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60; p = 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV‐1 outbreak ten years ago in Athens, Greece. Transmission rate can be consid-ered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2022

3. A nationwide study about the dispersal patterns of the predominant HIV-1 subtypes A1 and B in Greece: Inference of the molecular transmission clusters

Author

Kostaki, E.G. Gova, M. Adamis, G. Xylomenos, G. Chini, M. Mangafas, N. Lazanas, M. Metallidis, S. Tsachouridou, O. Papastamopoulos, V. Chatzidimitriou, D. Kakalou, E. Antoniadou, A. Papadopoulos, A. Psichogiou, M. Basoulis, D. Pilalas, D. Papageorgiou, I. Paraskeva, D. Chrysos, G. Paparizos, V. Kourkounti, S. Sambatakou, H. Bolanos, V. Sipsas, N.V. Lada, M. Barbounakis, E. Kantzilaki, E. Panagopoulos, P. Petrakis, V. Drimis, S. Gogos, C. Hatzakis, A. Beloukas, A. Skoura, L. Paraskevis, D.

Abstract

Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2–1518 subtype A1 sequences and 168 MTCs in the range of 2–218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34, p < 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05, p < 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57, p = 0.019), younger age (OR = 0.96, p < 0.001), and more recent sampling (time period: 2011–2015 vs. 1999–2005, OR = 3.83, p < 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2020

8. Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003-2015: Transmitted drug resistance is due to onward transmissions

Author

Paraskeva, D., Kostaki, Evangelia-Georgia, Magiorkinis, Gkikas, Gargalianos, Panagiotis, Xylomenos, G., Magiorkinis, Emmanouil, Lazanas, Marios, Chini, M., Nikolopoulos, Georgios K., Skoutelis, A., Papastamopoulos, V., Antoniadou, Anastasia, Papadopoulos, A., Psichogiou, M., Daikos, Georgios L., Oikonomopoulou, M., Zavitsanou, A., Chrysos, Georgios, Paparizos, V., Kourkounti, S., Sambatakou, H., Sipsas, N. V., Lada, M., Panagopoulos, P., Maltezos, E., Drimis, S., Hatzakis, A., Nikolopoulos, Georgios K.[0000-0002-3307-0246], Magiorkinis, Gkikas [0000-0002-0141-4753], Magiorkinis, Emmanouil [0000-0001-8883-7275], Psichogiou, M. [0000-0002-3000-8447], Gargalianos, Panagiotis [0000-0001-7070-8635], Antoniadou, Anastasia [0000-0003-0991-9198], and Kostaki, Evangelia-Georgia [0000-0002-3346-0930]

Subjects
0301 basic medicine, Microbiology (medical), Male, Genotype, Local transmission networks, Anti-HIV Agents, Resistance, Human immunodeficiency virus (HIV), HIV Infections, Drug resistance, Biology, medicine.disease_cause, Microbiology, law.invention, Therapy naive, 03 medical and health sciences, law, Drug Resistance, Viral, Genetics, medicine, Antiretroviral treatment, Prevalence, Humans, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Phylogeny, Nnrtis, Phylogenetic analysis, Greece, Hiv-1, Onward transmissions, virus diseases, Virology, Drug-naïve, 030104 developmental biology, Infectious Diseases, Transmission (mechanics), Mutation, HIV-1, Female, medicine.drug
Abstract

Background The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. Methods HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003–30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. Results The proportion of sequences with SDRMs was 5.98% (n = 205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. Conclusions The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients. © 2017 Elsevier B.V. 54 183 191

Published
2017

9. Transmission dynamics of HIV-1 drug resistance among treatment-naïve individuals in Greece: The added value of molecular epidemiology to public health

Author

Paraskevis, D. Kostaki, E. Gargalianos, P. Xylomenos, G. Lazanas, M. Chini, M. Skoutelis, A. Vasileiospapastamopoulos Paraskeva, D. Antoniadou, A. Papadopoulos, A. Psichogiou, M. Daikos, G.L. Chrysos, G. Paparizos, V. Kourkounti, S. Sambatakou, H. Sipsas, N.V. Lada, M. Panagopoulos, P. Maltezos, E. Drimis, S. Hatzakis, A.

Abstract

The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number (Re) of the locally transmitted NNRTI resistance. We analyzed sequences with dominant NNRTI resistance mutations (E138A and K103N) found within monophyletic clusters (local transmission networks (LTNs)) from patients in Greece. For the K103N LTN, the Re was >1 between 2008 and the first half of 2013. For all E138A LTNs, the Re was >1 between 1998 and 2015, except the most recent one (E138A_4), where the Re was >1 between 2006 and 2011 and approximately equal to 1 thereafter. K103N and E138A_4 showed similar characteristics with a more recent origin, higher Re during the first years of the sub-epidemics, and a declining trend in the number of transmissions during the last two years. In the remaining LTNs the epidemic was still expanding. Our study highlights the added value of molecular epidemiology to public health. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2017

10. Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003–2015: Transmitted drug resistance is due to onward transmissions

Author

Paraskevis, D. Kostaki, E. Magiorkinis, G. Gargalianos, P. Xylomenos, G. Magiorkinis, E. Lazanas, M. Chini, M. Nikolopoulos, G. Skoutelis, A. Papastamopoulos, V. Antoniadou, A. Papadopoulos, A. Psichogiou, M. Daikos, G.L. Oikonomopoulou, M. Zavitsanou, A. Chrysos, G. Paparizos, V. Kourkounti, S. Sambatakou, H. Sipsas, N.V. Lada, M. Panagopoulos, P. Maltezos, E. Drimis, S. Hatzakis, A.

Subjects
virus diseases
Abstract

Background The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. Methods HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003–30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. Results The proportion of sequences with SDRMs was 5.98% (n = 205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. Conclusions The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients. © 2017 Elsevier B.V.

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. Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003–2015: Transmitted drug resistance is due to onward transmissions

Author

Paraskevis, D., primary, Kostaki, E., additional, Magiorkinis, G., additional, Gargalianos, P., additional, Xylomenos, G., additional, Magiorkinis, E., additional, Lazanas, M., additional, Chini, M., additional, Nikolopoulos, G., additional, Skoutelis, A., additional, Papastamopoulos, V., additional, Antoniadou, A., additional, Papadopoulos, A., additional, Psichogiou, M., additional, Daikos, G.L., additional, Oikonomopoulou, M., additional, Zavitsanou, A., additional, Chrysos, G., additional, Paparizos, V., additional, Kourkounti, S., additional, Sambatakou, H., additional, Sipsas, N.V., additional, Lada, M., additional, Panagopoulos, P., additional, Maltezos, E., additional, Drimis, S., additional, and Hatzakis, A., additional

Published
2017
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13. 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

14. 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

15. 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

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

Author

Universitat Rovira i Virgili, Hofstra LM, Sauvageot N, Albert J, Alexiev I, Garcia F, Struck D, Van de Vijver DAMC, 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, Zidovec Lepej S, Boucher CAB, Schmit JC, Wensing AMJ,, Puchhammer-Stockl E, Sarcletti M, Schmied B, Geit M, Balluch G, Vandamme AM, Vercauteren J, Derdelinckx I, Sasse A, Bogaert M, Ceunen H, De Roo A, De Wit S, Echahidi F, Fransen K, Goffard JC, Goubau P, Goudeseune E, Yombi JC, Lacor P, Liesnard C, Moutschen M, Pierard D, Rens R, Schrooten Y, Vaira D, Vandekerckhove LPR, Van den Heuvel A, Van Der Gucht B, Van Ranst M, Van Wijngaerden E, Vandercam B, Vekemans M, Verhofstede C, Clumeck N, Lepej SZ, Begovac J, Kostrikis L, Demetriades I, Kousiappa I, Demetriou V, Hezka J, Maly M, Machala L, Jørgensen LB, 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 GL, Sipsas NV, Kontos A, Gamaletsou MN, Koratzanis G, Sambatakou H, 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, Lamber, Universitat Rovira i Virgili, and Hofstra LM, Sauvageot N, Albert J, Alexiev I, Garcia F, Struck D, Van de Vijver DAMC, 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, Zidovec Lepej S, Boucher CAB, Schmit JC, Wensing AMJ,, Puchhammer-Stockl E, Sarcletti M, Schmied B, Geit M, Balluch G, Vandamme AM, Vercauteren J, Derdelinckx I, Sasse A, Bogaert M, Ceunen H, De Roo A, De Wit S, Echahidi F, Fransen K, Goffard JC, Goubau P, Goudeseune E, Yombi JC, Lacor P, Liesnard C, Moutschen M, Pierard D, Rens R, Schrooten Y, Vaira D, Vandekerckhove LPR, Van den Heuvel A, Van Der Gucht B, Van Ranst M, Van Wijngaerden E, Vandercam B, Vekemans M, Verhofstede C, Clumeck N, Lepej SZ, Begovac J, Kostrikis L, Demetriades I, Kousiappa I, Demetriou V, Hezka J, Maly M, Machala L, Jørgensen LB, 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 GL, Sipsas NV, Kontos A, Gamaletsou MN, Koratzanis G, Sambatakou H, 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, Lamber

Abstract

© The Author 2015. 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 susceptibi

Published
2016

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

Author

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

Abstract

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

Published
2014

18. Calcific shoulder periarthritis (tendinitis) in adult onset diabetes mellitus: a controlled study.

Author

Mavrikakis, M E, Drimis, S, Kontoyannis, D A, Rasidakis, A, Moulopoulou, E S, and Kontoyannis, S

Abstract

Two groups, one of 824 adult diabetics and one of 320 age and sex matched non-diabetics, were examined for abnormal glucose metabolism and calcifications on anteroposterior shoulder x rays. Two hundred and sixty two (31.8%) of the diabetics had shoulder calcification compared with 33 (10.3%) of the control group, with a preponderant localisation in the right shoulder. Diabetes of long duration treated with insulin for a long time was associated with a larger percentage of shoulder calcifications. These data and previous laboratory findings suggest a possible pathogenetic correlation between the prevalence of calcific shoulder tendinitis and diabetes. [ABSTRACT FROM PUBLISHER]

Published
1989
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20. Estimation of the determinants for HIV late presentation using the traditional definition and molecular clock-inferred dates: Evidence that older age, heterosexual risk group and more recent diagnosis are prognostic factors.

Author

Kostaki EG, Limnaios S, Adamis G, Xylomenos G, Chini M, Mangafas N, Lazanas M, Patrinos S, Metallidis S, Tsachouridou O, Papastamopoulos V, Chatzidimitriou D, Antoniadou A, Papadopoulos A, Protopapas K, Tsiara C, Psichogiou M, Basoulis D, Pilalas D, Paraskeva D, Chrysos G, Paparizos V, Kourkounti S, Sambatakou H, Bolanos V, Sipsas NV, Lada M, Barbounakis E, Kantzilaki E, Panagopoulos P, Petrakis V, Drimis S, Katsarolis I, Lagiou P, Hatzakis A, Magiorkinis G, Skoura L, and Paraskevis D

Subjects
Male, Humans, Aged, Heterosexuality, Homosexuality, Male, Prognosis, Delayed Diagnosis, CD4 Lymphocyte Count, Risk Factors, HIV Infections diagnosis, Sexual and Gender Minorities, Acquired Immunodeficiency Syndrome
Abstract

Objectives: HIV late presentation (LP) has been increasing in recent years in Europe. Our aim was to investigate the characteristics of LP in Greece using in addition to the traditional definition for LP, the time interval between HIV infection and diagnosis., Methods: Our nationwide sample included HIV-1 sequences generated from 6166 people living with HIV (PLWH) in Greece during the period 1999-2015. Our analysis was based on the molecularly inferred HIV-1 infection dates for PLWH infected within local molecular transmission clusters of subtypes A1 and B., Results: Analysis of the determinants of LP was conducted using either CD4 counts or AIDS-defining condition at diagnosis or the time from infection to diagnosis. Older age, heterosexual transmission risk group and more recent diagnosis were associated with increased risk for LP. In contrast to previous studies, people who inject drugs (PWID) had a shorter median time to diagnosis (0.63 years) compared to men who have sex with men (MSM) (1.72 years) and heterosexuals (2.43 years). Using HIV infection dates that provide an unbiased marker for LP compared to CD4 counts at diagnosis, which are age-dependent, we estimated that the time to diagnosis increased gradually with age. Migrants infected regionally do not differ with respect to LP status compared to native Greeks., Conclusions: We demonstrate that older people and heterosexuals are among those at higher risk for LP; and given the growing number of older people among newly diagnosed cases, tailored interventions are needed in these populations., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Published
2022
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21. Dating the Origin and Estimating the Transmission Rates of the Major HIV-1 Clusters in Greece: Evidence about the Earliest Subtype A1 Epidemic in Europe.

Author

Limnaios S, Kostaki EG, Adamis G, Astriti M, Chini M, Mangafas N, Lazanas M, Patrinos S, Metallidis S, Tsachouridou O, Papastamopoulos V, Kakalou E, Chatzidimitriou D, Antoniadou A, Papadopoulos A, Psichogiou M, Basoulis D, Gova M, Pilalas D, Paraskeva D, Chrysos G, Paparizos V, Kourkounti S, Sambatakou H, Bolanos V, Sipsas NV, Lada M, Barbounakis E, Kantzilaki E, Panagopoulos P, Maltezos E, Drimis S, Sypsa V, Lagiou P, Magiorkinis G, Hatzakis A, Skoura L, and Paraskevis D

Subjects
Cluster Analysis, Europe epidemiology, Female, Greece epidemiology, HIV Infections transmission, Humans, Male, Sexual and Gender Minorities, Epidemics, HIV Infections epidemiology, HIV Infections virology, HIV-1 classification, HIV-1 genetics
Abstract

Our aim was to estimate the date of the origin and the transmission rates of the major local clusters of subtypes A1 and B in Greece. Phylodynamic analyses were conducted in 14 subtype A1 and 31 subtype B clusters. The earliest dates of origin for subtypes A1 and B were in 1982.6 and in 1985.5, respectively. The transmission rate for the subtype A1 clusters ranged between 7.54 and 39.61 infections/100 person years (IQR: 9.39, 15.88), and for subtype B clusters between 4.42 and 36.44 infections/100 person years (IQR: 7.38, 15.04). Statistical analysis revealed that the average difference in the transmission rate between the PWID and the MSM clusters was 6.73 (95% CI: 0.86 to 12.60; p = 0.026). Our study provides evidence that the date of introduction of subtype A1 in Greece was the earliest in Europe. Transmission rates were significantly higher for PWID than MSM clusters due to the conditions that gave rise to an extensive PWID HIV-1 outbreak ten years ago in Athens, Greece. Transmission rate can be considered as a valuable measure for public health since it provides a proxy of the rate of epidemic growth within a cluster and, therefore, it can be useful for targeted HIV prevention programs.

Published
2022
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22. A Nationwide Study about the Dispersal Patterns of the Predominant HIV-1 Subtypes A1 and B in Greece: Inference of the Molecular Transmission Clusters.

Author

Kostaki EG, Gova M, Adamis G, Xylomenos G, Chini M, Mangafas N, Lazanas M, Metallidis S, Tsachouridou O, Papastamopoulos V, Chatzidimitriou D, Kakalou E, Antoniadou A, Papadopoulos A, Psichogiou M, Basoulis D, Pilalas D, Papageorgiou I, Paraskeva D, Chrysos G, Paparizos V, Kourkounti S, Sambatakou H, Bolanos V, Sipsas NV, Lada M, Barbounakis E, Kantzilaki E, Panagopoulos P, Petrakis V, Drimis S, Gogos C, Hatzakis A, Beloukas A, Skoura L, and Paraskevis D

Subjects
Adult, Cluster Analysis, DNA, Viral genetics, Female, Genotype, Greece epidemiology, Humans, Male, Middle Aged, Phylogeography, Prevalence, Epidemiological Monitoring, HIV Infections epidemiology, HIV Infections transmission, HIV-1 classification, Phylogeny
Abstract

Our aim was to investigate the dispersal patterns and parameters associated with local molecular transmission clusters (MTCs) of subtypes A1 and B in Greece (predominant HIV-1 subtypes). The analysis focused on 1751 (28.4%) and 2575 (41.8%) sequences of subtype A1 and B, respectively. Identification of MTCs was based on phylogenetic analysis. The analyses identified 38 MTCs including 2-1518 subtype A1 sequences and 168 MTCs in the range of 2-218 subtype B sequences. The proportion of sequences within MTCs was 93.8% (1642/1751) and 77.0% (1982/2575) for subtype A1 and B, respectively. Transmissions within MTCs for subtype A1 were associated with risk group (Men having Sex with Men vs. heterosexuals, OR = 5.34, p < 0.001) and Greek origin (Greek vs. non-Greek origin, OR = 6.05, p < 0.001) and for subtype B, they were associated with Greek origin (Greek vs. non-Greek origin, OR = 1.57, p = 0.019), younger age (OR = 0.96, p < 0.001), and more recent sampling (time period: 2011-2015 vs. 1999-2005, OR = 3.83, p < 0.001). Our findings about the patterns of across and within country dispersal as well as the parameters associated with transmission within MTCs provide a framework for the application of the study of molecular clusters for HIV prevention.

Published
2020
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23. Transmission Dynamics of HIV-1 Drug Resistance among Treatment-Naïve Individuals in Greece: The Added Value of Molecular Epidemiology to Public Health.

Author

Paraskevis D, Kostaki E, Gargalianos P, Xylomenos G, Lazanas M, Chini M, Skoutelis A, Papastamopoulos V, Paraskeva D, Antoniadou A, Papadopoulos A, Psichogiou M, Daikos GL, Chrysos G, Paparizos V, Kourkounti S, Sambatakou H, Sipsas NV, Lada M, Panagopoulos P, Maltezos E, Drimis S, and Hatzakis A

Abstract

The presence of human immunodeficiency virus type 1 (HIV-1) drug resistance among drug-naïve patients remains stable, although the proportion of patients with virological failure to therapy is decreasing. The dynamics of transmitted resistance among drug-naïve patients remains largely unknown. The prevalence of non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance was 16.9% among treatment-naïve individuals in Greece. We aimed to investigate the transmission dynamics and the effective reproductive number ( R e ) of the locally transmitted NNRTI resistance. We analyzed sequences with dominant NNRTI resistance mutations (E138A and K103N) found within monophyletic clusters (local transmission networks (LTNs)) from patients in Greece. For the K103N LTN, the R e was >1 between 2008 and the first half of 2013. For all E138A LTNs, the R e was >1 between 1998 and 2015, except the most recent one (E138A&#95;4), where the R e was >1 between 2006 and 2011 and approximately equal to 1 thereafter. K103N and E138A&#95;4 showed similar characteristics with a more recent origin, higher R e during the first years of the sub-epidemics, and a declining trend in the number of transmissions during the last two years. In the remaining LTNs the epidemic was still expanding. Our study highlights the added value of molecular epidemiology to public health., Competing Interests: The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Published
2017
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24. Transmission of HIV Drug Resistance and the Predicted Effect on Current First-line Regimens in Europe.

Author

Hofstra LM, Sauvageot N, Albert J, Alexiev I, Garcia F, Struck D, Van de Vijver DAMC, 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, Zidovec Lepej S, Boucher CAB, Schmit JC, Wensing AMJ, Puchhammer-Stockl E, Sarcletti M, Schmied B, Geit M, Balluch G, Vandamme AM, Vercauteren J, Derdelinckx I, Sasse A, Bogaert M, Ceunen H, De Roo A, De Wit S, Echahidi F, Fransen K, Goffard JC, Goubau P, Goudeseune E, Yombi JC, Lacor P, Liesnard C, Moutschen M, Pierard D, Rens R, Schrooten Y, Vaira D, Vandekerckhove LPR, 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 SZ, Begovac J, Kostrikis L, Demetriades I, Kousiappa I, Demetriou V, Hezka J, Linka M, Maly M, Machala L, Nielsen C, Jørgensen LB, 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 GL, Sipsas NV, Kontos A, Gamaletsou MN, Koratzanis G, Sambatakou H, 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 MC, Rossi C, Prati F, Tramuto F, Vitale F, Ciccozzi M, Angarano G, Rezza G, Kolupajeva T, Vasins O, Griskevicius A, Lipnickiene V, Schmit JC, Struck D, Sauvageot N, Hemmer R, Arendt V, Michaux C, Staub T, Sequin-Devaux C, Wensing AMJ, Boucher CAB, van de Vijver DAMC, van Kessel A, van Bentum PHM, Brinkman K, Connell BJ, van der Ende ME, Hoepelman IM, van Kasteren M, Kuipers M, Langebeek N, Richter C, Santegoets RMWJ, Schrijnders-Gudde L, Schuurman R, van de Ven BJM, Åsjö B, Kran AB, Ormaasen V, Aavitsland P, Horban A, Stanczak JJ, Stanczak GP, 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 AM, Cernat R, Chiriac C, Dumitrescu F, Prisecariu LJ, Stanojevic M, Jevtovic D, 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 JL, de Mendoza C, Delgado R, Gutiérrez F, Berenguer J, Garcia-Bujalance S, Stella N, de Los Santos I, Blanco JR, Dalmau D, Rivero M, Segura F, Elías MJP, Alvarez M, Chueca N, Rodríguez-Martín C, Vidal C, Palomares JC, Viciana I, Viciana P, Cordoba J, Aguilera A, Domingo P, Galindo MJ, Miralles C, Del Pozo MA, Ribera E, Iribarren JA, 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, Karlsson A, Blaxhult A, Gisslén M, Svennerholm B, Bergbrant I, Björkman P, Säll C, Mellgren Å, Lindholm A, Kuylenstierna N, Montelius R, Azimi F, Johansson B, Carlsson M, Johansson E, Ljungberg B, Ekvall H, Strand A, Mäkitalo S, Öberg S, Holmblad P, Höfer M, Holmberg H, Josefson P, and Ryding U

Subjects
Adult, Europe, Female, HIV Infections drug therapy, HIV Protease Inhibitors pharmacology, HIV-1 genetics, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Mutation, Prevalence, Reverse Transcriptase Inhibitors pharmacology, Anti-HIV Agents pharmacology, Drug Resistance, Viral genetics, HIV Infections virology, HIV-1 drug effects
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 by Oxford University Press for the Infectious Diseases Society of America.)

Published
2016
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25. Patterns of drug resistance among newly diagnosed HIV-1 infected patients in Greece during the last decade: the crucial role of transmission networks.

Author

Paraskevis D, Zavitsanou A, Magiorkinis E, Gargalianos P, Xylomenos G, Lazanas M, Chini M, Skoutelis A, Papastamopoulos V, Antoniadou A, Papadopoulos A, Psichogiou M, Daikos G, Vassilakis A, Chrysos G, Paparizos V, Kourkounti S, Sambatakou H, Kordossis T, Koratzanis G, Panagopoulos P, Maltezos E, Drimis S, and Hatzakis A

Abstract

Introduction: The prevalence of drug resistance is approximately 10% in Europe and North America among newly infected patients. We aim to investigate the temporal patterns of resistance among drug naive HIV-infected individuals in Greece and also to determine transmission networking among those with resistant strains., Materials and Methods: Protease (PR) and partial reverse transcriptase (RT) sequences were determined from 2499 newly diagnosed HIV-1 patients, in Greece, during 2003-2013. Genotypic drug resistance was estimated using the HIVdb: Genotypic Resistance Interpretation Algorithm. We identified transmission clusters of resistant strains on the basis of a large collection of HIV-1 sequences from 4024 seropositives in Greece. Phylodynamic analysis was performed using a Bayesian method., Results: We estimated drug resistance levels among naïve patients on the basis of all resistance mutations in PR and partial RT. The overall prevalence of resistance was 19.6% (490/2499). Resistance to NNRTIs was the most common (397/2499, 15.9%) followed by PIs (116/2499, 4.6%) and NRTIs (79/2499, 3.2%). We found a significant trend for decreasing resistance to NRTIs over time (6.7%-1.6%). There was no time trend for the overall PI and NNRTI resistance. The most frequently observed major resistant sites in PR were V82 (2.0%) and L90 (1.8%). In RT, we found E138 (58.6%), K103 (13.1%), V179 (8.4%) and T215 (7.1%), M41 (4.7%) associated with resistance to NNRTIs and NRTIs, respectively. The prevalence of K103N and E138Q were significantly increased during 2003-2013. Crucially, we found that both K103N, E138Q are associated with transmission networking within men having sex with men (MSM) and intravenous drug user (IDU) local networks. The K103N network included seropositives across Greece, while the latter only from the recent IDU outbreak in Athens metropolitan area (1). Phylodynamic analyses revealed that the exponential growth for K103N network started in 2009 (Figure 1) and for the E138Q in 2010., Conclusions: The overall resistance has been stable in Greece over time; however, specific NNRTI resistance patterns are increasing. Notably, they are associated with local transmission networking, thus suggesting that this is the cause for the increased patterns of NNRTI resistance and not multiple transmissions of resistant strains from different sources among treated individuals. Our study highlights the advance of molecular epidemiology for understanding the dynamics of resistance.

Published
2014
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