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

Author

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

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

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

Published
2014

102. 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

104. Impact of HIV-1 subtype on CD4 count at HIV seroconversion, rate of decline, and viral load set point in European seroconverter cohorts

Author

Touloumi, G., Pantazis, N., Pillay, D., Paraskevis, D., Chaix, M.-L., Bucher, H. C., Kucherer, C., Zangerle, R., Kran, A.-M. B., Porter, K., Kelleher, A. D., Cooper, D. A., Grey, P., Finlayson, R., Bloch, M., Kelleher, T., Ramacciotti, T., Gelgor, L., Cooper, D., Smith, D., Gill, J., Jorgensen, L. B., Lutsar, I., Chene, G., Dabis, F., Thiebaut, R., Masquelier, B., Costagliola, D., Guiguet, M., Vanhems, P., Ghosn, J., Goujard, C., Meyer, L., Boufassa, F., Hamouda, O., Bartmeyer, B., Katsarou, O., Paparizos, V., Gargalianos-Kakolyris, P., Lazanas, M., Rezza, G., Dorrucci, M., Monforte, A. d., De Luca, A., Prins, M., Geskus, R., van der Helm, J., Schuitemaker, H., Sannes, M., Brubakk, O., Bakken Kran, A.-M., Rosinska, M., Muga, R., Tor, J., Garcia de Olalla, P., Cayla, J., del Amo, J., Moreno, S., Monge, S., Del Amo, J., del Romero, J., Perez-Hoyos, S., Rickenbach, M., Francioli, P., Malyuta, R., Brettle, R., Murphy, G., Sabin, C., Johnson, A., Phillips, A., Babiker, A., and Delpech, V.

Subjects
Microbiology (medical), Adult, Male, Genotype, Anti-HIV Agents, Human immunodeficiency virus (HIV), HIV Infections, Drug resistance, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), HIV Seropositivity, medicine, Humans, 030212 general & internal medicine, Seroconversion, 030304 developmental biology, HIV-1 subtype, 0303 health sciences, Molecular Epidemiology, Molecular epidemiology, business.industry, Middle Aged, Viral Load, medicine.disease, CD4 decline, Set point, 3. Good health, CD4 Lymphocyte Count, Europe, Infectious Diseases, Treatment Outcome, natural history, Immunology, HIV-1, Female, business, set point, Viral load
Abstract

Background. Human immunodeficiency virus type 1 (HIV-1) subtype may influence disease progression. We compared CD4 lymphocyte cell count levels at seroconversion, decline rates and viral load set point in individuals infected with different HIV-1 subtypes. Methods. We used data from the Concerted Action on SeroConversion to AIDS and Death in Europe (CASCADE) collaboration, restricted to those infected since 1996, aged >= 15 years, and applied mixed effects models for CD4 cell count decline and median regression for viral load set point (mean level 6-24 months from seroconversion). Results. The analysis included 3364 seroconverters with known HIV-1 subtypes. Compared with subtype B, CD4 at seroconversion was significantly higher for subtype CRF01 and lower for subtype C. Subsequent CD4 decline was significantly slower for subtypes A and CRF02 and marginally slower for subtype C compared with B. Mean CD4 loss at 2 years of seroconversion for white men exposed through sex between men, aged 30-39 years, having seroconverted since 2006, enrolled within 6 months of seroconversion, and without acute infection was 88, 142, 100, 130, 103, and 167 cells/mu L for subtypes A, B, C, CRF01_AE, CRF02_AG, and G, respectively. In adjusted analysis, median viral load set point and time to clinical AIDS/death did not differ significantly by subtype, although all subtypes, except C, tended to have lower levels compared with B. Conclusions. HIV-1 subtype significantly influences seroconversion CD4 cell levels and decline rates but not viral load set point. These findings may be helpful to HIV-positive individuals and their attending physicians in understanding disease progression.

Published
2013

105. HIV-1 subtype distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics

Author

Abecasis, A.B. Wensing, A.M.J. Paraskevis, D. Vercauteren, J. Theys, K. Van de Vijver, D.A.M.C. Albert, J. Asjö, B. Balotta, C. Beshkov, D. Camacho, R.J. Clotet, B. De Gascun, C. Griskevicius, A. Grossman, Z. Hamouda, O. Horban, A. Kolupajeva, T. Korn, K. Kostrikis, L.G. Kücherer, C. Liitsola, K. Linka, M. Nielsen, C. Otelea, D. Paredes, R. Poljak, M. Puchhammer-Stöckl, E. Schmit, J.-C. Sönnerborg, A. Stanekova, D. Stanojevic, M. Struck, D. Boucher, C.A.B. Vandamme, A.-M.

Abstract

Background: Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes.Results: We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual procedure that included phylogenetic tree and recombination analysis. The most prevalent subtypes/CRFs in our dataset were subtype B (66.1%), followed by sub-subtype A1 (6.9%), subtype C (6.8%) and CRF02_AG (4.7%). Substantial differences in the proportion of new diagnoses with distinct subtypes were found between European countries: the lowest proportion of subtype B was found in Israel (27.9%) and Portugal (39.2%), while the highest was observed in Poland (96.2%) and Slovenia (93.6%). Other subtypes were significantly more diagnosed in immigrant populations. Subtype B was significantly more diagnosed in men than in women and in MSM > IDUs > heterosexuals. Furthermore, the subtype distribution according to continent of origin of the patients suggests they acquired their infection there or in Europe from compatriots.Conclusions: The association of subtype with demographic parameters suggests highly compartmentalized epidemics, determined by social and behavioural characteristics of the patients. © 2013 Abecasis et al.; licensee BioMed Central Ltd.

Published
2013

106. The burden of transmitted drug resistance in clinical practice in Europe is increasing over time despite a stable prevalence

Author

Hofstra, M, Sauvageot, N, Albert, J, Alexiev, I, Garcia, F, Struck, D, Vercauteren, J, Van de Vijver, D, Åsjö, B, Balotta, C, Beshkov, D, Camacho, R, Coughlan, C, Griskevicius, A, Hamouda, O, Horban, A, Kolupajeva, T, Kostrikis, L, Kücherer, C, Liitsola, K, Linka, M, Mor, O, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, D, Poljak, Mario, Puchhammer-Stöckl, E, Somnerborg, A, Stanekova, D, Stanojević, M, Van Vaethem, K, Van Wijngaerclen, E, Židovec Lepej, Snježana, Bucher, C, Schmit, JC, and Wensing, A.

Subjects
virus diseases, transmitted drug resistance, clinical practice, Europe, prevalence
Abstract

Objectives: In the last decade, we showed that 1 in 10 patients newly diagnosed with HIV-1 in Europe is infected with a virus that harbours transmitted drug resistance mutations (TDR). We estimated the proportion and total number of HIV-1 diagnoses with TDR in Europe over time. Methods: Clinical and virological data from 8479 patients within 6 months of diagnosis with HIV-1 in 2002-2010 were analyzed. TDR (as defined by the 2009 WHO list) was determined for all 26 countries as the weighted sum of the prevalence per risk group per country, considering their share in the European HIV-1 epidemic. To estimate the annual number of HIV-1 diagnoses with TDR for the 19 countries that participated in surveillance since 2003 (Austria, Belgium, Cyprus, Czech Republic, Denmark, Finland, Germany, Greece, Ireland, Israel, Italy, Luxembourg, Netherlands, Norway, Poland, Serbia, Slovenia, Spain, Sweden), the weighted prevalence was multiplied by their total number of new HIV-1 diagnoses as reported by ECDC. Results: In 2008-2010, the prevalence of TDR was 9.2% (95%CI:7.3-11.1). Mutations associated with resistance to NRTIs were observed most frequently (5.1% ; 95%CI: 3.6-6.6), followed by NNRTIs (3.7% ; 95%CI: 2.3-5.0) and PIs (2.3% ; 95%CI: 1.3-3.2). Given the increasing number of HIV-1 diagnoses in these 19 countries, the estimated annual number of new diagnoses with HIV-TDR increased from 1010 (95% CI: 876-1144) in 2003-2005 to 1370 (95%CI:1127-1613) in 2008-2010 (p0.01). The increasing number of new diagnoses with NNRTI-resistance mutations (336 (95%CI:255-418) in 2003-2005 to 550 (95%CI:376-724) in 2008-2010 ; p0.03) is of particular concern, considering these mutations generally confer high-level resistance to NNRTIs that are frequently used as first-line therapy. Conclusion: Although the proportion of new HIV-1 diagnoses with TDR remains stable around 10%, the burden of TDR in clinical practices is increasing, underlining the importance of baseline genotypic testing and continuance of surveillance of TDR.

Published
2013

107. The State of Hepatitis B and C in the Mediterranean and Balkan Countries: Report from a Summit Conference

Author

Hatzakis, A. Van Damme, P. Alcorn, K. Gore, C. and Benazzouz, M. Berkane, S. Buti, M. Carballo, M. Cortes Martins, H. Deuffic-Burban, S. Dominguez, A. Donoghoe, M. and Elzouki, A-N. Bouafif, N. Ben-Alaya Esmat, G. Esteban, R. Fabri, M. Fenton, K. Goldberg, D. Goulis, I. and Hadjichristodoulou, T. Hatzigeorgiou, T. Hamouda, O. and Hasurdjiev, S. Hughes, S. Kautz, A. Malik, M. and Manolakopoulos, S. Maticic, M. Papatheodoridis, G. Peck, R. and Peterle, A. Potamitis, G. Prati, D. Roudot-Thoraval, F. and Reic, T. Sharara, A. Shennak, M. Shiha, G. Shouval, D. Socan, M. Thomas, H. Thursz, M. Tosti, M. Trepo, C. Vince, A. Vounou, E. Wiessing, L. Manns, M.

Abstract

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

Published
2013

112. Risk of new AIDS defining events in patients with advanced immunodeficiency during suppressive HAART: results from the German ClinSurv cohort

Author

Zoufaly, A, Kreuzberg, C, an der Heiden, M, Kollan, C, Hamouda, O, van Lunzen, J, and ClinSurv Studiengruppe

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Background: Despite recent advances in the reduction of morbidity and mortality after the advent of HAART, a large number of HIV patients still present late with advanced immunodeficiency. In these patients the risk of developing AIDS-defining events (ADE) may depend on a solid immune reconstitution[for full text, please go to the a.m. URL], 10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Published
2010
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113. Langfristige Wirksamkeit einer Zweitlinien-Therapie bei HIV-Infektion nach virologischem Versagen der Erstlinien-Therapie

Author

Brunner, J, Seybold, U, Gunsenheimer-Bartmeyer, B, Hamouda, O, Bogner, J, and ClinSurv-Studiengemeinschaft

Subjects
ddc: 610, 610 Medical sciences, Medicine
Abstract

Hintergrund: Während für die Initialtherapie der HIV-Infektion evidenzbasierte Empfehlungen für die Auswahl der antiretroviralen Kombinationstherapie (cART) bestehen, existieren zur Secondline-Therapie nach erstem virologischen Versagen kaum Studien zur Langzeiteffektivität. Ziel[for full text, please go to the a.m. URL], 10. Kongress für Infektionskrankheiten und Tropenmedizin (KIT 2010)

Published
2010
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114. Large multistate outbreak of norovirus gastroenteritis associated with frozen strawberries, East Germany, 2012

Author

Bernard, H., Faber, M., Wilking, H., Haller, S., Höhle, Michael, Schielke, A., Ducomble, T., Siffczyk, C., Merbecks, S. S., Fricke, G., Hamouda, O., Stark, K., Werber, D., Bernard, H., Faber, M., Wilking, H., Haller, S., Höhle, Michael, Schielke, A., Ducomble, T., Siffczyk, C., Merbecks, S. S., Fricke, G., Hamouda, O., Stark, K., and Werber, D.

Abstract

From 20 September through 5 October 2012, the largest recorded food-borne outbreak in Germany occurred. Norovirus was identified as the causative agent. We conducted four analytical epidemiological studies, two case–control studies and two surveys (in total 150 cases) in secondary schools in three different federal states. Overall, 390 institutions in five federal states reported nearly 11,000 cases of gastroenteritis. They were predominantly schools and childcare facilities and were supplied almost exclusively by one large catering company. The analytical epidemiological studies consistently identified dishes containing strawberries as the most likely vehicle, with estimated odds ratios ranging from 2.6 to 45.4. The dishes had been prepared in different regional kitchens of the catering company and were served in the schools two days before the peaks of the respective outbreaks. All affected institutions had received strawberries of one lot, imported frozen from China. The outbreak vehicle was identified within a week, which led to a timely recall and prevented more than half of the lot from reaching the consumer. This outbreak exemplifies the risk of large outbreaks in the era of global food trade. It underlines the importance of timely surveillance and epidemiological outbreak investigations for food safety.

Published
2014

115. Patterns of transmitted HIV drug resistance in Europe vary by risk group

Author

Frentz, D. (Dineke), Vijver, D.A.M.C. (David) van de, Abecasis, A.B. (Ana), Albert, J. (Jan), Hamouda, O. (Osamah), Jørgensen, L.B. (Louise), Kücherer, C. (Claudia), Struck, D. (Daniel), Schmit, J.-C. (Jean-Claude), Vercauteren, J. (Jurgen), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Bergin, P., Beshkov, D. (Danail), Camacho, R.J. (Ricardo Jorge), Clotet, B. (Bonaventura), Griskevicius, A. (Algirdas), Grossman, Z. (Zehava), Horban, A. (Andrzej), Kolupajeva, T. (Tatjana), Korn, K. (Klaus), Kostrikis, L.G. (Leondios), Linka, K.L.M. (Kirsi Liitsola Marek), Nielsen, C. (Claus), Otelea, D. (Dan), Paraskevis, D. (Dimitrios), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Vandamme, A.M. (Anne Mieke), Boucher, C.A.B. (Charles), Wensing, A.M.J. (Annemarie), Frentz, D. (Dineke), Vijver, D.A.M.C. (David) van de, Abecasis, A.B. (Ana), Albert, J. (Jan), Hamouda, O. (Osamah), Jørgensen, L.B. (Louise), Kücherer, C. (Claudia), Struck, D. (Daniel), Schmit, J.-C. (Jean-Claude), Vercauteren, J. (Jurgen), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Bergin, P., Beshkov, D. (Danail), Camacho, R.J. (Ricardo Jorge), Clotet, B. (Bonaventura), Griskevicius, A. (Algirdas), Grossman, Z. (Zehava), Horban, A. (Andrzej), Kolupajeva, T. (Tatjana), Korn, K. (Klaus), Kostrikis, L.G. (Leondios), Linka, K.L.M. (Kirsi Liitsola Marek), Nielsen, C. (Claus), Otelea, D. (Dan), Paraskevis, D. (Dimitrios), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Vandamme, A.M. (Anne Mieke), Boucher, C.A.B. (Charles), and Wensing, A.M.J. (Annemarie)

Abstract

Background: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. Methods: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. Results: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non- nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively). Conclusions: MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs.

Published
2014
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116. Patterns of Transmitted HIV Drug Resistance in Europe Vary by Risk Group

Author

Frentz, Dineke, van de Vijver, David, Abecasis, A, Albert, J (Jan), Hamouda, O, Jorgensen, L, Kucherer, C, Struck, D, Schmit, JC, Vercauteren, J, Asjo, B, Balotta, C, Bergin, C, Beshkov, D, Camacho, R, Clotet, B, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, L, Linka, KLM, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Sonnerborg, A, Stanekova, D, Stanojevic, M, Vandamme, AM, Boucher, Charles, Wensing, A, Frentz, Dineke, van de Vijver, David, Abecasis, A, Albert, J (Jan), Hamouda, O, Jorgensen, L, Kucherer, C, Struck, D, Schmit, JC, Vercauteren, J, Asjo, B, Balotta, C, Bergin, C, Beshkov, D, Camacho, R, Clotet, B, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, L, Linka, KLM, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Sonnerborg, A, Stanekova, D, Stanojevic, M, Vandamme, AM, Boucher, Charles, and Wensing, A

Abstract

Background: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. Methods: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. Results: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (<1 year) (p<0.001). The prevalence of TDRM was highest in MSM (prevalence of 11.1%), followed by heterosexuals (6.6%) and IDU (5.1%, p<0.001). TDRM was predominantly ascribed to nucleoside reverse transcriptase inhibitors (NRTI) with a prevalence of 6.6% in MSM, 3.3% in heterosexuals and 2.0% in IDU (p = 0.001). A significant increase in resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs) and a decrease in resistance to protease inhibitors was observed in MSM (p = 0.008 and p = 0.006, respectively), but not in heterosexual patients (p = 0.68 and p = 0.14, respectively). Conclusions: MSM showed to have significantly higher TDRM prevalence compared to heterosexuals and IDU. The increasing NNRTI resistance in MSM is likely to negatively influence the therapy response of first-line therapy, as most include NNRTI drugs.

Published
2014

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

Author

Frentz, Dineke, van de Vijver, David, Abecasis, AB, Albert, J (Jan), Hamouda, O, Jorgensen, LB, Kucherer, C, Struck, D, Schmit, JC, Vercauteren, J, Asjo, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Sonnerborg, A, Stanekova, D, Stanojevic, M, van Wijngaerden, E, Wensing, AMJ, Boucher, Charles, Frentz, Dineke, van de Vijver, David, Abecasis, AB, Albert, J (Jan), Hamouda, O, Jorgensen, LB, Kucherer, C, Struck, D, Schmit, JC, Vercauteren, J, Asjo, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Sonnerborg, A, Stanekova, D, Stanojevic, M, van Wijngaerden, E, Wensing, AMJ, and Boucher, Charles

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 (wTDRM) 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.

Published
2014

118. Tracing the HIV-1 subtype B mobility in Europe: A phylogeographic approach

Author

Paraskevis, D. Pybus, O. Magiorkinis, G. Hatzakis, A. Wensing, A.M.J. van de Vijver, D.A. Albert, J. Angarano, G. Åsjö, B. Balotta, C. Boeri, E. Camacho, R. Chaix, M.-L. Coughlan, S. Costagliola, D. De Luca, A. de Mendoza, C. Derdelinckx, I. Grossman, Z. Hamouda, O. Hoepelman, I.M. Horban, A. Korn, K. Kücherer, C. Leitner, T. Loveday, C. MacRae, E. Maljovic-Berry, I. Meyer, L. Nielsen, C. Op de Coul, E.L.M. Ormaasen, V. Perrin, L. Puchhammer-Stöckl, E. Ruiz, L. Salminen, M.O. Schmit, J.-C. Schuurman, R. Soriano, V. Stanczak, J. Stanojevic, M. Struck, D. Van Laethem, K. Violin, M. Yerly, S. Zazzi, M. Boucher, C.A. Vandamme, A.-M.

Abstract

Background: The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced. Results: In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration. For Poland no significant migratory pathways were inferred. Conclusion: Subtype B phylogeographies provide a new insight about the geographical distribution of viral lineages, as well as the significant pathways of virus dispersal across Europe, suggesting that intervention strategies should also address tourists, travellers and migrants. © 2009 Paraskevis et al; licensee BioMed Central Ltd.

Published
2009

119. Tracing the HIV-1 subtype B mobility in Europe: a phylogeographic approach

Author

Paraskevis, D, Pybus, O, Magiorkinis, G, Hatzakis, A, Wensing, Am, Van De Vijver, David, Albert, Jan, Angarano, Gioacchino, Asjo, B, Balotta, Claudia, Boeri, E, Camacho, Ricardo, Chaix, Ml, Coughlan, S, Costagliola, D, De Luca, Andrea, De Mendoza, C, Derdelinckx, I, Grossmann, Z, Hamouda, O, Hoepelman, I, Horban, A, Korn, K, Kucherer, C, Leitner, T, and Spread, Programme

Subjects
epidemiology, phylogenesis, HIV-1 subtype B, Settore MED/17 - MALATTIE INFETTIVE
Published
2009

120. Transmission of drug-resistant HIV-1 is stabilizing in Europe

Author

Vercauteren, J., Wensing, A. M. J., Van De Vijver, D. A. M. C., Albert, Jan, Balotta, Claudia, Hamouda, O., Kücherer, C., Struck, D., Schmit, J. -C, Åsjö, Birgitta, Bruckova, M., Camacho, Ricardo J., Clotet, B., Coughlan, S., Grossman, Z., Horban, A., Korn, K., Kostrikis, Leontios G., Nielsen, C., Paraskevis, Dimitrios N., Poljak, M., Puchhammer-Stöckl, E., Riva, C., Ruiz, L., Salminen, M., Schuurman, R., Sonnerborg, A., Stanekova, D., Stanojevic, M., Vandamme, A. M., Boucher, C. A. B., Paraskevis, Dimitrios [0000-0001-6167-7152], and Virology

Subjects
Male, Human immunodeficiency virus (HIV), Human immunodeficiency virus 1, HIV Infections, RNA directed DNA polymerase inhibitor, Drug resistance, medicine.disease_cause, Gastroenterology, law.invention, 0302 clinical medicine, law, middle aged, Prevalence, Immunology and Allergy, genetics, 030212 general & internal medicine, disease transmission, 0303 health sciences, biology, adult, drug effect, article, Middle Aged, virus transmission, 3. Good health, Europe, Infectious Diseases, Transmission (mechanics), female, priority journal, Lentivirus, Cohort, Reverse Transcriptase Inhibitors, health program, Female, Adult, medicine.medical_specialty, prevalence, Virus, 03 medical and health sciences, SDG 3 - Good Health and Well-being, male, Human immunodeficiency virus infection, antiviral resistance, Internal medicine, Drug Resistance, Viral, medicine, proteinase inhibitor, Humans, Protease inhibitor (pharmacology), controlled study, human, 030306 microbiology, nucleotide sequence, biology.organism_classification, Human immunodeficiency virus 1 infection, Virology, major clinical study, Confidence interval, unindexed sequence, HIV-1
Abstract

The SPREAD Programme investigated prospectively the time trend from September 2002 through December 2005 of transmitted drug resistance (TDR) among 2793 patients in 20 European countries and in Israel with newly diagnosed human immunodeficiency virus type 1 (HIV-1) infection. The overall prevalence of TDR was 8.4% (225 of 2687 patients 95% confidence interval [CI], 7.4%-9.5%), the prevalence of nucleoside reverse-transcriptase inhibitor (NRTI) resistance was 4.7% (125 of 2687 patients 95% CI, 3.9%-5.5%), the prevalence of nonucleoside reverse-transcriptase inhibitor (NNRTI) resistance was 2.3% (62 of 2687 patients 95% CI, 1.8%-2.9%), and the prevalence of protease inhibitor (PI) resistance was 2.9% (79 of 2687 patients 95% CI, 2.4%-3.6%). There was no time trend in the overall TDR or in NRTI resistance, but there was a statistically significant decrease in PI resistance (Pp.04) and in NNRTI resistance after an initial increase (Pp.02). We found that TDR appears to be stabilizing in Europe, consistent with recent reports of decreasing drug resistance and improved viral suppression in patients treated for HIV-1 infection. © 2009 by the Infectious Diseases Society of America. All rights reserved. 200 1503 1508 Cited By :190

Published
2009

122. The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes

Author

Vijver, D.A. van de, Wensing, A.M.J., Angarano, G., Asjo, B., Balotta, C., Camacho, R., Chaix, M., Costagliola, D., De Luca, A., Derdelinckx, I., Grossman, Z., Hamouda, O., Hatzakis, A., Hemmer, R., Hoepelman, A.I.M., Horban, A., Korn, K., Kücherer, C., Leitner, T., Loveday, C., MacRae, E., Maljkovic, I., Mendoza, C. de, Meyer, L., Nielsen, C., Op de Coul, E.L.M., Omaasen, V., Paraskevis, D., Perrin, L., Puchhammer-Stöckl, E., Salminen, M., Schmit, J., Scheider, F., Schuurman, R., Soriano, V., Stanczak, G., Stanojevic, M., Vandamme, A., Laethem, K. van, Violin, M., Wilde, K., Yerly, S., Zazzi, M., and Boucher, C.A.B.

Subjects
Geneeskunde, drug resistance, HIV, non-B subtypes, genetic barrier
Abstract

The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug resistance substitutions. This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (9600 of non-B subtype) isolated from antiretroviral- naive patients in Europe. Methods: The genetic barrier was calculated as the sum of transitions (scored as 1) and/or transversions (2.5) required for evolution to any major drug resistance substitution. In addition, the number of minor protease substitutions was determined for every subtype. Results: Few dissimilarities were found. An increased genetic barrier was calculated for I82A (subtypes C and G), V108I (subtype G), V118I (subtype G), Q151M (subtypes D and F), L210W (subtypes C, F, G, and CRF02_AG), and P225H (subtype A) (P G 0.001 compared with subtype B). A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P G 0.001 vs subtype B). Conversely, minor protease substitutions differed extensively between subtypes. Conclusions: Based on the calculated genetic barrier, the rate of drug resistance development may be similar for different HIV-1 subtypes. Because of differences in minor protease substitutions, protease inhibitor resistance could be enhanced in particular subtypes once the relevant major substitutions are selected. Key Words: HIV, non-B subtypes, drug resistance, genetic barrier

Published
2006

123. The calculated genetic barrier for antiretroviral drug resistance substitutions is largely similar for different HIV-1 subtypes

Author

van de Vijver, DA Wensing, AMJ Angarano, G Asjo, B and Balotta, C Boeri, E Camacho, R Chaix, ML Costagliola, D and De Luca, A Derdelinckx, I Grossman, Z Hamouda, O and Hatzakis, A Hemmer, R Hoepelman, A Horban, A Korn, K and Kucherer, C Leitner, T Loveday, C MacRae, E Maljkovic, I and de Mendoza, C Meyer, L Nielsen, C de Coul, ELMO and Ormaasen, V Paraskevis, D Perrin, L Puchhammer-Stockl, E and Ruiz, L Salminen, M Schmit, JC Schneider, F Schuurman, R and Soriano, V Stanczak, G Stanojevic, M Vandamme, AM and Van Laethem, K Violin, M Wilbe, K Yerly, S Zazzi, M and Boucher, CAB SPREAD Programme

Abstract

Background: The genetic barrier, defined as the number of mutations required to overcome drug-selective pressure, is an important factor for the development of HIV drug resistance. Because of high variability between subtypes, particular HIV-1 subtypes could have different genetic barriers for drug resistance substitutions. This study compared the genetic barrier between subtypes using some 2000 HIV-1 sequences (> 600 of non-B subtype) isolated from antiretroviral-naive patients in Europe. Methods: The genetic barrier was calculated as the sum of transitions (scored as 1) and/or transversions (2.5) required for evolution to any major drug resistance substitution. In addition, the number of minor protease substitutions was determined for every subtype. Results: Few dissimilarities were found. An increased genetic barrier was calculated for 182A (subtypes C and G), V 1081 (subtype G), V 1181 (subtype G), Q 15 1 M (subtypes D and F), L210W (subtypes C, F, G, and CRF02_AG), and P225H (subtype A) (P < 0.001 compared with subtype B). A decreased genetic barrier was found for I82T (subtypes C and G) and V106M (subtype C) (P < 0.001 vs subtype B). Conversely, minor protease substitutions differed extensively between subtypes. Conclusions: Based on the calculated genetic barrier, the rate of drug resistance development may be similar for different HIV-1 subtypes. Because of differences in minor protease substitutions, protease inhibitor resistance could be enhanced in particular subtypes once the relevant major substitutions are selected.

Published
2006

126. Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: Implications for clinical management

Author

Wensing, AMJ van de Vijver, DA Angarano, G Asjo, B and Balotta, C Boeri, E Camacho, R Chaix, ML Costagliola, D and De Luca, A Derdelinckx, I Grossman, Z Hamouda, O and Hatzakis, A Hemmer, R Hoepelman, A Horban, A Korn, K and Kucherer, C Leitner, T Loveday, C MacRae, E Maljkovic, I and de Mendoza, C Meyer, L Nielsen, C de Coul, ELO and Ormaasen, V Paraskevis, D Perrin, L Puchhammer-Stockl, E and Ruiz, L Salminen, M Schmit, JC Schneider, F Schuurman, R and Soriano, V Stanczak, G Stanojevic, M Vandamme, AM and Van Laethem, K Violin, M Wilbe, K Yerly, S Zazzi, M and Boucher, CA SPREAD Programme

Abstract

Background. Infection with drug-resistant human immunodeficiency virus type 1 (HIV-1) can impair the response to combination therapy. Widespread transmission of drug-resistant variants has the disturbing potential of limiting future therapy options and affecting the efficacy of postexposure prophylaxis. Methods. We determined the baseline rate of drug resistance in 2208 therapy-naive patients recently and chronically infected with HIV-1 from 19 European countries during 1996-2002. Results. In Europe, 1 of 10 antiretroviral-naive patients carried viruses with >= 1 drug-resistance mutation. Recently infected patients harbored resistant variants more often than did chronically infected patients (13.5% vs. 8.7%; P = .006). Non-B viruses (30%) less frequently carried resistance mutations than did subtype B viruses (4.8% vs. 12.9%;). Baseline resistance increased over time in newly diagnosed cases of non-B infection: from P

Published
2005

127. Short-term risk of AIDS according to current CD4 cell count and viral load in antiretroviral drug-naive individuals and those treated in the monotherapy era

Author

Beral, V, Coutinho, R, Darbyshire, J, Del Amo, J, Gill, N, Lee, C, Meyer, L, Rezza, G, Porter, K, Babiker, A, Walker, AS, Tyrer, F, Dabis, F, Thiebaut, R, Chene, G, Lawson-Ayayi, S, Boufassa, F, Vanhems, P, Hamouda, O, Fischer, K, Pezzotti, P, Touloumi, G, Hatzakis, A, Karafoulidou, A, Katsarou, O, Brettle, R, Sabin, C, Johnson, AM, Phillips, AN, Darbyshire, JH, Day, NE, De Angelis, D, del Romero, J, Aguado, IH, Perez-Hoyos, S, Muga, R, van Asten, L, van Benthem, B, Prins, M, Kirk, O, Pedersen, C, Eskild, A, Briuun, JN, Sannes, M, Francioli, P, Egger, M, Rickenbach, M, Cooper, D, Kaldor, J, Ashton, L, Vizzard, J, and Collaboration, CASCADE

Published
2004

129. Assessment of Ambiguous Base Calls in HIV-1 pol Population Sequences as a Biomarker for Identification of Recent Infections in HIV-1 Incidence Studies

Author

Meixenberger, K., primary, Hauser, A., additional, Jansen, K., additional, Yousef, K. P., additional, Fiedler, S., additional, von Kleist, M., additional, Norley, S., additional, Somogyi, S., additional, Hamouda, O., additional, Bannert, N., additional, Bartmeyer, B., additional, and Kucherer, C., additional

Published
2014
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130. Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Author

Mocroft, A, Lundgren, JD, Sabin, ML, D'Arminio Monforte, A, Brockmeyer, N, Casabona, J, Castagna, A, Costagliola, D, Dabis, F, De Wit, S, Fätkenheuer, G, Furrer, H, Johnson, AM, Lazanas, MK, Leport, C, Moreno, S, Obel, N, Post, FA, Reekie, J, Reiss, P, Sabin, C, Skaletz-Rorowski, A, Suarez-Lozano, I, Torti, C, Warszawski, J, Zangerle, R, Fabre-Colin, C, Kjaer, J, Chene, G, Grarup, J, Kirk, O, Sabin, M, Suarez-Loano, I, Touloumi, G, Meyer, L, Krause, MM, Ghosn, J, de Wolf, F, Prins, M, Bucher, H, Gibb, D, Hamouda, O, Bartmeyer, B, Del Amo, J, Thorne, C, Stephan, C, Pérez-Hoyos, S, Noguera-Julian, A, Antinori, A, Ramos, J, Battegay, M, Rauch, A, Mussini, C, Tookey, P, Miró, JM, Goetghebuer, T, Teira, R, Garrido, M, Judd, A, Haerry, D, Weller, I, Schwimmer, C, Termote, M, Touzeau, G, Campbell, M, Friis-Møller, N, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Dorrucci, M, Egger, M, Engsig, F, Lambotte, O, Lewden, C, Lodwick, R, Matheron, S, Miro, J, Paredes, R, Phillips, A, Puoti, M, Scherrer, A, Smit, C, Sterne, J, Thiebaut, R, von Wyl, V, Wittkop, L, Mocroft, A, Lundgren, JD, Sabin, ML, D'Arminio Monforte, A, Brockmeyer, N, Casabona, J, Castagna, A, Costagliola, D, Dabis, F, De Wit, S, Fätkenheuer, G, Furrer, H, Johnson, AM, Lazanas, MK, Leport, C, Moreno, S, Obel, N, Post, FA, Reekie, J, Reiss, P, Sabin, C, Skaletz-Rorowski, A, Suarez-Lozano, I, Torti, C, Warszawski, J, Zangerle, R, Fabre-Colin, C, Kjaer, J, Chene, G, Grarup, J, Kirk, O, Sabin, M, Suarez-Loano, I, Touloumi, G, Meyer, L, Krause, MM, Ghosn, J, de Wolf, F, Prins, M, Bucher, H, Gibb, D, Hamouda, O, Bartmeyer, B, Del Amo, J, Thorne, C, Stephan, C, Pérez-Hoyos, S, Noguera-Julian, A, Antinori, A, Ramos, J, Battegay, M, Rauch, A, Mussini, C, Tookey, P, Miró, JM, Goetghebuer, T, Teira, R, Garrido, M, Judd, A, Haerry, D, Weller, I, Schwimmer, C, Termote, M, Touzeau, G, Campbell, M, Friis-Møller, N, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Dorrucci, M, Egger, M, Engsig, F, Lambotte, O, Lewden, C, Lodwick, R, Matheron, S, Miro, J, Paredes, R, Phillips, A, Puoti, M, Scherrer, A, Smit, C, Sterne, J, Thiebaut, R, von Wyl, V, and Wittkop, L

Abstract

Background:Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality.Methods and Findings:LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43).Conclusions:LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals af

Published
2013

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

Author

Frentz, D. (Dineke), Wensing, A.M.J. (Annemarie), Albert, J. (Jan), Paraskevis, D. (Dimitrios), Abecasis, A.B. (Ana), Hamouda, O. (Osamah), Jørgensen, L.B. (Louise), Kücherer, C. (Claudia), Struck, D. (Daniel), Schmit, J.-C. (Jean-Claude), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Beshkov, D. (Danail), Camacho, R.J. (Ricardo Jorge), Clotet, B. (Bonaventura), Coughlan, S. (Suzie), De Wit, S., Griskevicius, A. (Algirdas), Grossman, Z. (Zehava), Horban, A. (Andrzej), Kolupajeva, T. (Tatjana), Korn, K. (Klaus), Kostrikis, L.G. (Leondios), Liitsola, K. (Kirsi), Linka, M. (Marek), Nielsen, C. (Claus), Otelea, D. (Dan), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Vandamme, A.M. (Anne Mieke), Boucher, C.A.B. (Charles), Vijver, D.A.M.C. (David) van de, Frentz, D. (Dineke), Wensing, A.M.J. (Annemarie), Albert, J. (Jan), Paraskevis, D. (Dimitrios), Abecasis, A.B. (Ana), Hamouda, O. (Osamah), Jørgensen, L.B. (Louise), Kücherer, C. (Claudia), Struck, D. (Daniel), Schmit, J.-C. (Jean-Claude), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Beshkov, D. (Danail), Camacho, R.J. (Ricardo Jorge), Clotet, B. (Bonaventura), Coughlan, S. (Suzie), De Wit, S., Griskevicius, A. (Algirdas), Grossman, Z. (Zehava), Horban, A. (Andrzej), Kolupajeva, T. (Tatjana), Korn, K. (Klaus), Kostrikis, L.G. (Leondios), Liitsola, K. (Kirsi), Linka, M. (Marek), Nielsen, C. (Claus), Otelea, D. (Dan), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Vandamme, A.M. (Anne Mieke), Boucher, C.A.B. (Charles), and Vijver, D.A.M.C. (David) van de

Abstract

Background: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe.Results: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 20

Published
2013
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132. HIV-1 subtype distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics

Author

Abecasis, A.B. (Ana), Wensing, A.M.J. (Annemarie), Paraskevis, D. (Dimitrios), Vercauteren, J. (Jurgen), Theys, K. (Kristof), Vijver, D.A.M.C. (David) van de, Albert, J. (Jan), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Beshkov, D. (Danail), Camacho, R.J. (Ricardo Jorge), Clotet, B., Gascun, C. (Cillian) de, Griskevicius, A. (Algirdas), Grossman, Z. (Zehava), Hamouda, O. (Osamah), Horban, A. (Andrzej), Kolupajeva, T. (Tatjana), Korn, K., Kostrikis, L.G. (Leondios), Kücherer, C. (Claudia), Liitsola, K. (Kirsi), Linka, M. (Marek), Nielsen, C. (Claus), Otelea, D. (Dan), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Schmit, J.-C. (Jean-Claude), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Struck, D. (Daniel), Boucher, C.A.B. (Charles), Vandamme, A.M. (Anne Mieke), Abecasis, A.B. (Ana), Wensing, A.M.J. (Annemarie), Paraskevis, D. (Dimitrios), Vercauteren, J. (Jurgen), Theys, K. (Kristof), Vijver, D.A.M.C. (David) van de, Albert, J. (Jan), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Beshkov, D. (Danail), Camacho, R.J. (Ricardo Jorge), Clotet, B., Gascun, C. (Cillian) de, Griskevicius, A. (Algirdas), Grossman, Z. (Zehava), Hamouda, O. (Osamah), Horban, A. (Andrzej), Kolupajeva, T. (Tatjana), Korn, K., Kostrikis, L.G. (Leondios), Kücherer, C. (Claudia), Liitsola, K. (Kirsi), Linka, M. (Marek), Nielsen, C. (Claus), Otelea, D. (Dan), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Schmit, J.-C. (Jean-Claude), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Struck, D. (Daniel), Boucher, C.A.B. (Charles), and Vandamme, A.M. (Anne Mieke)

Abstract

Background: Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes.Results: We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual

Published
2013
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133. HIV-1 subtype distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics

Author

Abecasis, AB, Wensing, AMJ, Paraskevis, D, Vercauteren, J, Theys, K, van de Vijver, David, Albert, J, Asjo, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, De Gascun, C, Griskevicius, A, Grossman, Z, Hamouda, O, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Kucherer, C, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Schmit, JC, Sonnerborg, A, Stanekova, D, Stanojevic, M, Struck, D, Boucher, Charles, Vandamme, AM, Abecasis, AB, Wensing, AMJ, Paraskevis, D, Vercauteren, J, Theys, K, van de Vijver, David, Albert, J, Asjo, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, De Gascun, C, Griskevicius, A, Grossman, Z, Hamouda, O, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Kucherer, C, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Schmit, JC, Sonnerborg, A, Stanekova, D, Stanojevic, M, Struck, D, Boucher, Charles, and Vandamme, AM

Abstract

Background: Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes. Results: We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual procedure that included phylogenetic tree and recombination analysis. The most prevalent subtypes/CRFs in our dataset were subtype B (66.1%), followed by sub-subtype A1 (6.9%), subtype C (6.8%) and CRF02_AG (4.7% Conclusions: The association of subtype with demographic parameters suggests highly compartmentalized epidemics, determined by social and behavioural characteristics of the patients.

Published
2013

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

Author

Frentz, Dineke, Wensing, AMJ, Albert, J, Paraskevis, D, Abecasis, AB, Hamouda, O, Jorgensen, LB, Kucherer, C, Struck, D, Schmit, JC, Asjo, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, de Wit, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Sonnerborg, A, Stanekova, D, Stanojevic, M, Vandamme, AM, Boucher, Charles, van de Vijver, David, Frentz, Dineke, Wensing, AMJ, Albert, J, Paraskevis, D, Abecasis, AB, Hamouda, O, Jorgensen, LB, Kucherer, C, Struck, D, Schmit, JC, Asjo, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, de Wit, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paredes, R, Poljak, M, Puchhammer-Stockl, E, Sonnerborg, A, Stanekova, D, Stanojevic, M, Vandamme, AM, Boucher, Charles, and van de Vijver, David

Abstract

Background: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe. Results: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included. We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 Conclusions: Our findings indicate that the transmission of HIV-1 in Europe is predominantly occurring between patients from the same country. This could have implications for HIV-1 transmission prevention programmes. Because infections through travelling between countries is not frequently observed it is important to have good surveillance of the national HIV-1 epidemics.

Published
2013

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

Author

Theys, K. (Kristof), Deforche, K. (Koen), Vercauteren, J. (Jurgen), Libin, P. (Pieter), Vijver, D.A.M.C. (David) van de, Albert, J. (Jan), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Bruckova, M. (Marie), Camacho, R.J. (Ricardo Jorge), Clotet, B. (Bonaventura), Coughlan, S. (Suzie), Grossman, Z. (Zehava), Hamouda, O. (Osamah), Horban, A. (Andrzej), Korn, K. (Klaus), Kostrikis, L.G. (Leondios), Kücherer, C. (Claudia), Nielsen, C. (Claus), Paraskevis, D. (Dimitrios), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Riva, C. (Chiara), Ruiz, L. (Lidia), Liitsola, K. (Kirsi), Schmit, J.-C. (Jean-Claude), Schuurman, R. (Rob), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Struck, D. (Daniel), Laethem, K. (Kristel) van, Wensing, A.M.J. (Annemarie), Boucher, C.A.B. (Charles), Vandamme, A.M. (Anne Mieke), Theys, K. (Kristof), Deforche, K. (Koen), Vercauteren, J. (Jurgen), Libin, P. (Pieter), Vijver, D.A.M.C. (David) van de, Albert, J. (Jan), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Bruckova, M. (Marie), Camacho, R.J. (Ricardo Jorge), Clotet, B. (Bonaventura), Coughlan, S. (Suzie), Grossman, Z. (Zehava), Hamouda, O. (Osamah), Horban, A. (Andrzej), Korn, K. (Klaus), Kostrikis, L.G. (Leondios), Kücherer, C. (Claudia), Nielsen, C. (Claus), Paraskevis, D. (Dimitrios), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Riva, C. (Chiara), Ruiz, L. (Lidia), Liitsola, K. (Kirsi), Schmit, J.-C. (Jean-Claude), Schuurman, R. (Rob), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Struck, D. (Daniel), Laethem, K. (Kristel) van, Wensing, A.M.J. (Annemarie), Boucher, C.A.B. (Charles), and Vandamme, A.M. (Anne Mieke)

Abstract

Background: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase

Published
2012
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136. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

Author

Theys, K, Deforche, K, Vercauteren, J, Libin, P, van de Vijver, David, Albert, J (Jan), Asjo, B, Balotta, C, Bruckova, M, Camacho, RJ, Clotet, B, Coughlan, S, Grossman, Z, Hamouda, O, Horban, A, Korn, K, Kostrikis, LG, Kucherer, C, Nielsen, C, Paraskevis, D, Poljak, M, Puchhammer-Stockl, E, Riva, C, Ruiz, L, Liitsola, K, Schmit, JC, Schuurman, R (Rob), Sonnerborg, A, Stanekova, D, Stanojevic, M, Struck, D, Van Laethem, K, Wensing, AMJ, Boucher, Charles, Vandamme, AM, Theys, K, Deforche, K, Vercauteren, J, Libin, P, van de Vijver, David, Albert, J (Jan), Asjo, B, Balotta, C, Bruckova, M, Camacho, RJ, Clotet, B, Coughlan, S, Grossman, Z, Hamouda, O, Horban, A, Korn, K, Kostrikis, LG, Kucherer, C, Nielsen, C, Paraskevis, D, Poljak, M, Puchhammer-Stockl, E, Riva, C, Ruiz, L, Liitsola, K, Schmit, JC, Schuurman, R (Rob), Sonnerborg, A, Stanekova, D, Stanojevic, M, Struck, D, Van Laethem, K, Wensing, AMJ, Boucher, Charles, and Vandamme, AM

Abstract

Background: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore are expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. Results: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during Conclusions: These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance

Published
2012

138. Tracing the HIV-1 subtype B mobility in Europe: A phylogeographic approach

Author

Paraskevis, D. (Dimitrios), Pybus, O. (Oliver), Magiorkinis, G. (Gkikas), Hatzakis, A. (Angelos), Wensing, A.M.J. (Annemarie), Vijver, D.A.M.C. (David) van de, Albert, J. (Jan), Angarano, G. (Guiseppe), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Boeri, E. (Enzo), Camacho, R.J. (Ricardo Jorge), Chaix, M.L. (Marie Laure), Coughlan, S. (Suzie), Costagliola, D. (Dominique), Luca, A. (Andrea) de, Mendoza, C. (Carmen) de, Derdelinck, I. (Inge), Grossman, Z. (Zehava), Hamouda, O. (Osamah), Hoepelman, I.M. (Ilja Mohandas), Horban, A. (Andrzej), Korn, K. (Klaus), Kücherer, C. (Claudia), Leitner, T. (Thomas), Loveday, C. (Clive), MacRae, E. (Eilidh), Maljovic-Berry, I. (Inam), Meyer, L. (Laurence), Nielsen, C. (Claus Vinther), Op de Coul, E.L.M. (Eline), Ormaasen, V. (Vidar), Perrin, L. (Luc Henri), Puchhammer-Stöckl, E. (Elisabeth), Ruiz, L. (Lidia), Paraskevis, D. (Dimitrios), Pybus, O. (Oliver), Magiorkinis, G. (Gkikas), Hatzakis, A. (Angelos), Wensing, A.M.J. (Annemarie), Vijver, D.A.M.C. (David) van de, Albert, J. (Jan), Angarano, G. (Guiseppe), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Boeri, E. (Enzo), Camacho, R.J. (Ricardo Jorge), Chaix, M.L. (Marie Laure), Coughlan, S. (Suzie), Costagliola, D. (Dominique), Luca, A. (Andrea) de, Mendoza, C. (Carmen) de, Derdelinck, I. (Inge), Grossman, Z. (Zehava), Hamouda, O. (Osamah), Hoepelman, I.M. (Ilja Mohandas), Horban, A. (Andrzej), Korn, K. (Klaus), Kücherer, C. (Claudia), Leitner, T. (Thomas), Loveday, C. (Clive), MacRae, E. (Eilidh), Maljovic-Berry, I. (Inam), Meyer, L. (Laurence), Nielsen, C. (Claus Vinther), Op de Coul, E.L.M. (Eline), Ormaasen, V. (Vidar), Perrin, L. (Luc Henri), Puchhammer-Stöckl, E. (Elisabeth), and Ruiz, L. (Lidia)

Abstract

Background: The prevalence and the origin of HIV-1 subtype B, the most prevalent circulating clade among the long-term residents in Europe, have been studied extensively. However the spatial diffusion of the epidemic from the perspective of the virus has not previously been traced. Results: In the current study we inferred the migration history of HIV-1 subtype B by way of a phylogeography of viral sequences sampled from 16 European countries and Israel. Migration events were inferred from viral phylogenies by character reconstruction using parsimony. With regard to the spatial dispersal of the HIV subtype B sequences across viral phylogenies, in most of the countries in Europe the epidemic was introduced by multiple sources and subsequently spread within local networks. Poland provides an exception where most of the infections were the result of a single point introduction. According to the significant migratory pathways, we show that there are considerable differences across Europe. Specifically, Greece, Portugal, Serbia and Spain, provide sources shedding HIV-1; Austria, Belgium and Luxembourg, on the other hand, are migratory targets, while for Denmark, Germany, Italy, Israel, Norway, the Netherlands, Sweden, Switzerland and the UK we inferred significant bidirectional migration.

Published
2009
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149. HIV-1 subtype distribution and its demographic determinants in newly diagnosed patients in Europe suggest highly compartmentalized epidemics

Author

Abecasis, A. B., Wensing, A. M. J., Paraskevis, Dimitrios N., Vercauteren, J., Theys, K., Van de Vijver, D. A. M. C., Albert, Jan, Åsjö, Birgitta, Balotta, Claudia, Beshkov, Danail, Camacho, Ricardo J., Clotet, B., De Gascun, C., Griskevicius, A., Grossman, Z., Hamouda, O., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, Leontios G., Kücherer, C., Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Schmit, J. -C, Sönnerborg, A., Stanekova, D., Stanojevic, M., Struck, D., Boucher, C. A. B., Vandamme, A. -M, Virology, and Paraskevis, Dimitrios [0000-0001-6167-7152]

Subjects
Male, demography, Slovenia, Human immunodeficiency virus (HIV), Human immunodeficiency virus 1, Distribution (economics), HIV Infections, medicine.disease_cause, molecular epidemiology, epidemic, Risk Factors, computer program, Epidemiology, Israel, cladistics, genetic recombination, 0303 health sciences, Phylogenetic tree, Transmission (medicine), adult, article, homosexuality, virus transmission, Subtyping, 3. Good health, Europe, female, Infectious Diseases, virus typing, Female, lcsh:Immunologic diseases. Allergy, medicine.medical_specialty, sex difference, intravenous drug abuse, immigrant, Newly diagnosed, Biology, 03 medical and health sciences, Risk-Taking, male, SDG 3 - Good Health and Well-being, Virology, medicine, Humans, human, phylogenetic tree, Social Behavior, Epidemics, 030304 developmental biology, Portugal, 030306 microbiology, business.industry, Research, Disease progression, heterosexuality, Bayes Theorem, Human immunodeficiency virus 1 infection, major clinical study, amino acid sequence, Socioeconomic Factors, HIV-1, Human medicine, Poland, lcsh:RC581-607, business, Demography
Abstract

Background: Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes.Results: We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual procedure that included phylogenetic tree and recombination analysis. The most prevalent subtypes/CRFs in our dataset were subtype B (66.1%), followed by sub-subtype A1 (6.9%), subtype C (6.8%) and CRF02_AG (4.7%). Substantial differences in the proportion of new diagnoses with distinct subtypes were found between European countries: the lowest proportion of subtype B was found in Israel (27.9%) and Portugal (39.2%), while the highest was observed in Poland (96.2%) and Slovenia (93.6%). Other subtypes were significantly more diagnosed in immigrant populations. Subtype B was significantly more diagnosed in men than in women and in MSM > IDUs > heterosexuals. Furthermore, the subtype distribution according to continent of origin of the patients suggests they acquired their infection there or in Europe from compatriots.Conclusions: The association of subtype with demographic parameters suggests highly compartmentalized epidemics, determined by social and behavioural characteristics of the patients. © 2013 Abecasis et al. licensee BioMed Central Ltd. 10 Tradenames: REGA Subtyping Cited By :55

Published
2013
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150. Prevalence of drug-resistant HIV-1 variants in untreated individuals in Europe: implications for clinical management

Author

Wensing, A.M.J., van de Vijver, D.A.M.C., Augarano, G., Asjo, B., Balotta, C., Boeri, E., Camacho, R., Chaix, M.L., Costagliola, D., De Luca, A., Derdelinckx, I., Grosman, Z., Hamouda, O., Hatzakis, A., Hemmer, R., Hoepelman, I.M., Horban, A., Korn, K., Kucherer, C., Leitner, T., Loveday, C., MacRae, E., Malikovic, I., Mendoza, C., Meyer, L., Nielsen, C., Op de Coul, E.L., Ormaassen, V., Paraskevis, D., Perrin, L., Puchhammer-Stockl, E., Ruiz, L., Salminen, M., Schmit, J.C., Schneider, F., Schuurman, R., Soriano, E., Stanzak, G., Stanojevic, M., Vandamme, A.M., Van Laethem, K., Violin, M., Wilbe, K., Yerly, S., Zazzi, M., Boucher, C.A.B., Wensing, A.M.J., van de Vijver, D.A.M.C., Augarano, G., Asjo, B., Balotta, C., Boeri, E., Camacho, R., Chaix, M.L., Costagliola, D., De Luca, A., Derdelinckx, I., Grosman, Z., Hamouda, O., Hatzakis, A., Hemmer, R., Hoepelman, I.M., Horban, A., Korn, K., Kucherer, C., Leitner, T., Loveday, C., MacRae, E., Malikovic, I., Mendoza, C., Meyer, L., Nielsen, C., Op de Coul, E.L., Ormaassen, V., Paraskevis, D., Perrin, L., Puchhammer-Stockl, E., Ruiz, L., Salminen, M., Schmit, J.C., Schneider, F., Schuurman, R., Soriano, E., Stanzak, G., Stanojevic, M., Vandamme, A.M., Van Laethem, K., Violin, M., Wilbe, K., Yerly, S., Zazzi, M., and Boucher, C.A.B.

Published
2005

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