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1. Optimization of a genotypic assay applicable to all human immunodeficiency virus type 1 protease and reverse transcriptase subtypes

Author: Snoeck, J., Riva, C., Steegen, K., Schrooten, Y., Maes, B., Vergne, L., Van Laethem, K., Peeters, M., and Vandamme, A.-M.
Published: 2005
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2. Evaluation of two interpretation algorithms for the prediction of drug susceptibility in non-B subtype viruses

Author: Snoeck, J, Van Laethem, K, Schrooten, Y, Derdelinckx, I, Van Wijngaerden, E, and Vandamme, A-M
Published: 2003

3. A14 Ultra-wide and ultra-deep sequencing increases the detection rate of dual HIV-1 infections and recombinants

Author: Van Laethem, K, primary, Thielen, A, additional, Schrooten, Y, additional, Ferreira, F, additional, Vinken, L, additional, and Daümer, M, additional
Published: 2018
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4. 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

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

Author: Moutschen, M., Hofstra, Laura Marije Arije, Sauvageot, Nicolas, Albert, Jan, Alexiev, Ivailo, Garcia, Federico, Struck, Daniel, Van, de Vijver, Åsjö, Birgitta, Beshkov, Danail, Coughlan, Suzie, Descamps, Diane, Griskevicius, Algirdas, Hamouda, Osamah, Horban, Andrzej, Van Kasteren, Marjo, Kolupajeva, Tatjana, Kostrikis, Leontios G., Liitsola, Kirsi, Linka, Marek, Mor, Orna, Nielsen, Claus, Otelea, Dan, Paraskevis, Dimitrios N., Paredes, Roger, Poljak, Mario, Puchhammer-Stöckl, Elisabeth, Sönnerborg, Anders, Staneková, Danica, Stanojevic, Maja, Van Laethem, Kristel, Zazzi, Maurizio, Zidovec Lepej, Snjezana, Boucher, Charles A. B., Schmit, Jean-Claude, Wensing, Annemarie M. J., Puchhammer-Stockl, E., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van, den Heuvel, Van, Der Gucht, Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Lepej, S. Z., Begovac, J., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Linka, M., Maly, M., Machala, L., Nielsen, C., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Liitsola, K., Ristola, M., Suni, J., Sutinen, J., Descamps, D., Assoumou, L., Castor, G., Grude, M., Flandre, P., Storto, A., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Zavitsanou, Assimina, Vassilakis, A., Lazanas, Marios C., Chini, Maria C., Lioni, A., Sakka, V., Kourkounti, Sofia, Paparizos, Vassilios A., Antoniadou, Anastasia C., Papadopoulos, Antonios I., Poulakou, Garyphallia G., Katsarolis, I., Protopapas, K., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Xylomenos, Georgios, Lourida, G., Psichogiou, Mina A., Daikos, George L., Sipsas, N. V., Kontos, Athanasios N., Gamaletsou, M. N., Koratzanis, Georgios, Sambatakou, H., Mariolis, H., Skoutelis, A., Papastamopoulos, V., Georgiou, O., Panagopoulos, Periklis, Maltezos, E., Coughlan, S., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Mor, O., Levi, I., Chemtob, D., Grossman, Z., Zazzi, M., de Luca, A., Balotta, Claudia, Riva, C., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Kolupajeva, T., Vasins, O., Griskevicius, A., Lipnickiene, V., Schmit, J. C., Struck, D., Hemmer, R., Arendt, V., Michaux, C., Staub, T., Sequin-Devaux, C., Wensing, A. M. J., Boucher, C. A. B., van, de Vijver, van Kessel, A., van Bentum, P. H. M., Brinkman, K., Connell, B. J., van, der Ende, Hoepelman, I. M., van Kasteren, M., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., Schuurman, R., van, de Ven, Kran, A. -M B., Ormaasen, V., Aavitsland, P., Horban, A., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Maolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Camacho, Ricardo J., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Otelea, D., Paraschiv, S., Tudor, A. M., Cernat, R., Chiriac, C., Dumitrescu, F., Prisecariu, L. J., Stanojevic, M., Jevtovic, Dj, Salemovic, D., Stanekova, D., Habekova, M., Chabadová, Z., Drobkova, T., Bukovinova, P., Shunnar, A., Truska, P., Poljak, M., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Garcia, F., Paredes, R., Monge, S., Moreno, S., del Amo, J., Asensi, V., Sirvent, J. L., de Mendoza, C., Delgado, R., Gutiérrez, F., Berenguer, J., Garcia-Bujalance, S., Stella, Natalia C., de, los Santos, Blanco, J. R., Dalmau, D., Rivero, M., Segura, F., Elıás, Marıá Jesús Pérez, Alvarez, M., Chueca, N., Rodríguez-Martín, C., Vidal, C., Palomares, J. C., Viciana, I., Viciana, P., Cordoba, J., Aguilera, A., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de, la Torre, Vidal, F., Clotet, B., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Sönnerborg, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, Per, Säll, C., Mellgren, Å., Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., Öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., Ryding, U., Van Kessel, A., Clinical sciences, Microbiology and Infection Control, Supporting clinical sciences, Clinicum, Department of Medicine, Virology, Cohorte de Adultos de la Red de Investigación en SIDA, Spain., SPREAD Program, [Hofstra,LM, Sauvageot,N, Struck,D, Schmit,JC ] Luxembourg Institute of Health, Luxembourg. [Hofstra,LM, Wensing,AMJ] Department of Virology, University Medical Center Utrecht, The Netherlands. [Albert,J, Sönnerborg,A] Karolinska Institute, Solna. Karolinska University Hospital, Stockholm, Sweden. [Alexiev,I, Beshkov,D] National Center of Infectious and Parasitic Diseases, Sofia, Bulgaria. [Garcia,F] Complejo Hospitalario Universitario de Granada. Instituto de Investigación IBS Granada, Spain. [Van de Vijver,DAMC, Boucher,CAB] Erasmus MC, University Medical Center, Rotterdam, The Netherlands. [Åsjö,B] University of Bergen, Norway. [Coughlan,S] University College Dublin, Ireland. [Descamps,D] AP-HP Groupe hospitalier Bichat-Claude Bernard. IAME INSERM UMR 1137. Université Paris Diderot Sorbonne Paris Cité, Paris, France. [Griskevicius,A] Lithuanian AIDS Center, Vilnius, Lithuania. [Hamouda,O] Robert Koch Institute, Berlin, Germany. [Horban,A] Hospital of Infectious Diseases, Warsaw, Poland. [Van Kasteren,M] St Elisabeth Hospital, Tilburg, The Netherlands. [Kolupajeva,T] Infectiology Center of Latvia, Riga. [Kostrikis,LG] University of Cyprus, Nicosia. [Liitsola,K] Department of Infectious Diseases, National Institute for Health and Welfare, Helsinki, Finland. [Linka,M] National Reference Laboratory for HIV/AIDS, National Institute of Public Health, Prague, Czech Republic. [Mor,O] National HIV Reference Laboratory, Chaim Sheba Medical Center, Tel-Hashomer, Israel. [Nielsen,C] Statens Serum Institut, Copenhagen, Denmark. [Otelea,D] National Institute for Infectious Diseases 'Prof. dr. Matei Bals', Bucharest, Romania. [Paraskevis,D] National Retrovirus Reference Center, University of Athens, Greece. [Paredes,R] IrsiCaixa Foundation, Badalona, Spain. [Poljak,M] Faculty of Medicine, Slovenian HIV/AIDS Reference Centre, University of Ljubljana, Slovenia. [Puchhammer-Stöckl,E] Medical University Vienna, Austria. [Staneková,D] Slovak Medical University, Bratislava, Slovakia. [Stanojevic,M] Faculty of Medicine, University of Belgrade, Serbia. [Van Laethem,K] Rega Institute for Medical Research, KU Leuven, Belgium. [Zazzi,M] University of Siena, Italy. [Zidovec Lepej,S] University Hospital for Infectious Diseases 'Dr. Fran Mihaljevic', Zagreb, Croatia., This work was supported by a CORE grant of Fond National de la Recherche Luxembourg (grant number C12/BM/4011111–HIV molecular epidemiology in Europe). This work has been partially supported by the European Commission (fifth framework, grant number QLK2-CT-2001-01344, sixth framework, grant number LSHP-CT-2006-518211, DynaNets grant number 233847, seventh framework, CHAIN grant number 223131), Belgium: Belgian AIDS Reference Laboratory Fund, Belgian Fonds voor Wetenschappelijk Onderzoek (grant number G.0692.14), Cyprus: Cyprus Research Promotion Foundation (grant number Health/0104/22), Denmark: Danish AIDS Foundation, France: Agence Nationale de Recherches sur le SIDA et les Hepatites Virales, Germany: Ministry of Health (grant number 1502-686-18), Ministry of Education and Research (grant number 01KI501), Italy: Fifth National Program on HIV/AIDS, Instituto Superiore di Sanità (grant numbers 40F.56 and 20D.1.6), Luxembourg: Fondation Recherche sur le SiDA and Ministry of Health, Republic of Serbia: Ministry of Education and Science (grant number 175024), Slovakia: project 'Center of Excellence of Environmental Health,' ITMS number 26240120033, based on supporting operational research and development program financed from the European Regional Development Fund, and Sweden: Swedish Research Council and Swedish Civil Contingencies Agency., APH - Health Behaviors & Chronic Diseases, Graduate School, Hofstra, LM, Sauvageot, N, Albert, J, Alexiev, I, Garcia, F, Struck, D, Van de Vijver, DA, Åsjö, B, Beshkov, D, Coughlan, S, Descamps, D, Griskevicius, A, Hamouda, O, Horban, A, Van Kasteren, M, Kolupajeva, T, Kostrikis, LG, Liitsola, K, Linka, M, Mor, O, Nielsen, C, Otelea, D, Paraskevis, D, Paredes, R, Poljak, M, Puchhammer-Stöckl, E, Sönnerborg, A, Staneková, D, Stanojevic, M, Van Laethem, K, Zazzi, M, Lepej, SZ, Boucher, CA, Schmit, JC, Wensing, AM, SPREAD program investigators, including Vitale F and Tramuto, F, Vandamme, Annemie, Vercauteren, Jurgen, Schrooten, Yoeri, Van Ranst, Marc, Van Wijngaerden, Eric, Derdelinckx, Inge, Camacho, Ricardo Jorge, Kostrikis, Leontios G. [0000-0002-5340-7109], and Paraskevis, Dimitrios [0000-0001-6167-7152]
Subjects: Male, Human immunodeficiency virus 1, Etravirine, RNA directed DNA polymerase inhibitor, darunavir, HIV Infections, Settore MED/42 - Igiene Generale E Applicata, Disciplines and Occupations::Health Occupations::Medicine::Public Health [Medical Subject Headings], Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Salud pública, genetics, Inhibidores de proteasas, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Vital Statistics::Morbidity::Prevalence [Medical Subject Headings], atazanavir, media_common, transmission, Geographicals::Geographic Locations::Europe [Medical Subject Headings], 3. Good health, microbial sensitivity test, priority journal, Europe, HIV-1, antiretroviral therapy, drug resistance, HIV/AIDS, lamivudine, Reverse Transcriptase Inhibitors/pharmacology, anti human immunodeficiency virus agent, Drug, Microbiology (medical), medicine.medical_specialty, antiviral susceptibility, Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation [Medical Subject Headings], media_common.quotation_subject, 030106 microbiology, HIV Infections/drug therapy, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Antiviral Agents::Anti-Retroviral Agents::Reverse Transcriptase Inhibitors [Medical Subject Headings], Microbial Sensitivity Tests, RILPIVIRINE, Article, EFAVIRENZ, 03 medical and health sciences, transmitted drug resistance, SDG 3 - Good Health and Well-being, Humans, Transmission, human, Phenomena and Processes::Physiological Phenomena::Pharmacological Phenomena::Drug Resistance [Medical Subject Headings], REVERSE-TRANSCRIPTASE INHIBITORS, Rilpivirina, INTEGRASE, MUTATIONS, abacavir, major clinical study, Virology, Infecciones por VIH, Regimen, Antiretroviral therapy, Drug resistance, Medicine (all), Infectious Diseases, chemistry, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Oxazines::Benzoxazines [Medical Subject Headings], Mutation, 0301 basic medicine, nevirapine, Communicable diseases, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Confidence Intervals [Medical Subject Headings], chemistry.chemical_compound, antiviral therapy, INFECTION, Medicine and Health Sciences, Prevalence, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Data Collection::Surveys and Questionnaires [Medical Subject Headings], Viral, Non-U.S. Gov't, Reverse-transcriptase inhibitor, antiretrovirus agent, Research Support, Non-U.S. Gov't, Human immunodeficiency virus infected patient, Middle Aged, virology, PREVALENCE, Encuestas y Cuestionarios, ANTIRETROVIRAL TREATMENT, HIV-1/drug effects, HIV Protease Inhibitors/pharmacology, Rilpivirine, Reverse Transcriptase Inhibitors, Diseases::Immune System Diseases::Immunologic Deficiency Syndromes::HIV Infections [Medical Subject Headings], Female, HIV drug resistance, medicine.drug, Adult, Human immunodeficiency virus proteinase inhibitor, Chemicals and Drugs::Organic Chemicals::Nitriles::Rilpivirine [Medical Subject Headings], Efavirenz, Anti-HIV Agents, Research Support, Resistencia a medicamentos, Settore MED/17 - MALATTIE INFETTIVE, antiviral resistance, Internal medicine, Anti-HIV Agents/pharmacology, Drug Resistance, Viral, Journal Article, medicine, Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Enzyme Inhibitors::Protease Inhibitors [Medical Subject Headings], abacavir plus lamivudine, Europa (Continente), HIV Protease Inhibitors, emtricitabine, nonhuman, Intervalos de confianza, Mutación, business.industry, HIV, prediction, Inhibidores de la transcriptasa inversa, Human immunodeficiency virus 1 infection, tenofovir, INDIVIDUALS, Drug Resistance, Viral/genetics, Benzoxazinas, ETRAVIRINE, drug effects, 3121 General medicine, internal medicine and other clinical medicine, Prevalencia, business
Abstract: Transmitted human immunodeficiency virus drug resistance in Europe is stable at around 8%. The impact of baseline mutation patterns on susceptibility to antiretroviral drugs should be addressed using clinical guidelines. The impact on baseline susceptibility is largest for nonnucleoside reverse transcriptase inhibitors., Background. Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore, guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD program systematically collects data to gain insight into TDR occurring in Europe since 2001. Methods. Demographic, clinical, and virological data from 4140 antiretroviral-naive human immunodeficiency virus (HIV)–infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002 to 2007. Baseline susceptibility to antiretroviral drugs was predicted using the Stanford HIVdb program version 7.0. Results. The overall prevalence of TDR did not change significantly over time and was 8.3% (95% confidence interval, 7.2%–9.5%) in 2008–2010. The most frequent indicators of TDR were nucleoside reverse transcriptase inhibitor (NRTI) mutations (4.5%), followed by nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations (2.9%) and protease inhibitor mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine, respectively, independent of current NRTI backbones. Conclusions. Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.
Published: 2016
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6. A18 Random amplification with next-generation sequencing to cover HIV and HCV full-length genomes

Author: Cuypers, L., primary, Conceição-Neto, N., additional, Dierickx, T., additional, Schrooten, Y., additional, Vrancken, B., additional, Van Wijngaerden, E., additional, Nevens, F., additional, Vandamme, A.-M., additional, Matthijnssens, J., additional, and Van Laethem, K., additional
Published: 2017
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7. 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

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

Author: Moutschen, M., Casadellà, M., van Ham, P. M., Noguera-Julian, M., van Kessel, A., Pou, C., Hofstra, Laura Marije Arije, Santos, J. R., Garcia, F., Struck, D., Alexiev, Ivailo, Bakken Kran, A. M., Hoepelman, A. I., Kostrikis, Leontios G., Somogyi, Sybille, Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paraskevis, Dimitrios N., Poljak, M., Puchhammer-Stöckl, E., Staneková, D., Stanojevic, M., Van Laethem, K., Zidovec Lepej, S., Clotet, B., Boucher, C. A. B., Paredes, R., Wensing, A. M. J., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Vandamme, A. M., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. C., Goubau, P., Goudeseune, E., Yombi, J. C., Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Beshkov, Danail, Begovac, J., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Machala, L., Maly, M., Jørgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Ristola, M., Suni, J., Sutinen, J., Hamouda, O., Kücherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Korn, K., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Chilomenos, G., Psichogiou, Mina A., Daikos, George L., Sabatakou, H., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., Wensing, A. M., Boucher, C. A., van de Vijver, D. A., van, P. H., Brinkman, K., Op de, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M., Schrijnders-Gudde, L., Schuurman, R., van de Ven, B. J., Åsjö, Birgitta, Bakken, A. M., Ormaasen, V., Aavitsland, P., Paraschiv, S., Tudor, A. M., Jevtovic, D., Salemovic, D., Stanekova, D., Habekova, M., Mokráš, Miloš, Truska, P., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Domingo, P., Galindo, M. J., Miralles, C., Del, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de la Torre, J., Vidal, F., Kostrikis, Leontios G. [0000-0002-5340-7109], and Paraskevis, Dimitrios [0000-0001-6167-7152]
Subjects: sequence analysis, genotype, Human immunodeficiency virus 1, HIV Infections, RNA directed DNA polymerase inhibitor, integrase strand transfer inhibitor, HIV Integrase, molecular epidemiology, Human immunodeficiency virus prevalence, Risk Factors, Antiretroviral Therapy, Highly Active, genetic variability, genetics, Stanford HIVdb score, clinical trial, Human immunodeficiency virus infected patient, highly active antiretroviral therapy, Viral Load, unclassified drug, virology, health survey, dolutegravir, Europe, female, risk factor, Population Surveillance, virus gene, raltegravir, amino acid substitution, p31 integrase protein, Human immunodeficiency virus 1, DNA sequence, gene sequence, Article, male, antiviral resistance, Drug Resistance, Viral, proteinase inhibitor, Humans, cross-sectional study, controlled study, human, HIV Integrase Inhibitors, quality control, scoring system, CD4 lymphocyte count, integrase inhibitor, Sequence Analysis, DNA, virus load, nonnucleoside reverse transcriptase inhibitor, Human immunodeficiency virus 1 infection, major clinical study, drug efficacy, Cross-Sectional Studies, multicenter study, drug effects, genetic variation, HIV-1, integrase
Abstract: Objectives: The objective of this study was to define the natural genotypic variation of the HIV-1 integrase gene across Europe for epidemiological surveillance of integrase strand-transfer inhibitor (InSTI) resistance. Methods: This was a multicentre, cross-sectional study within the European SPREAD HIV resistance surveillance programme. A representative set of 300 samples was selected from 1950 naive HIV-positive subjects newly diagnosed in 2006-07. The prevalence of InSTI resistance was evaluated using quality-controlled baseline population sequencing of integrase. Signature raltegravir, elvitegravir and dolutegravir resistance mutations were defined according to the IAS-USA 2014 list. In addition, all integrase substitutions relative to HXB2 were identified, including those with a Stanford HIVdb score=10 to at least one InSTI. To rule out circulation of minority InSTIresistant HIV, 65 samples were selected for 454 integrase sequencing. Results: For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIswere detected. Eleven (4%) subjects hadmutations at resistance-associated positions with an HIVdb score =10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutationsweredetected, whereas integrase substitutionswithanHIVdbscore=10were found in8(14.3%) individuals. Conclusions:No signature InSTI-resistant variantswere circulating in Europe before the introduction of InSTIs. However, polymorphisms contributing to InSTI resistancewere not rare. As InSTI use becomes more widespread, continuous surveillance of primary InSTI resistance is warranted. These data will be key to modelling the kinetics of InSTI resistance transmission in Europe in the coming years. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. 70 2885 2888 Cited By :15
Published: 2015

9. 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

10. 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

11. 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

12. 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

13. 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

14. Trends and predictors of transmitted drug resistance (TDR) and clusters with TDR in a local Belgian HIV-1 epidemic

Author: Pineda-Peña, A. -C, Schrooten, Y., Vinken, L., Ferreira, F., Li, G., Trovão, N. S., Khouri, R., Derdelinckx, I., De Munter, P., Kuc̈herer, C., Kostrikis, Leontios G., Nielsen, C., Littsola, K., Wensing, A., Stanojevic, M., Paredes, R., Balotta, Claudia, Albert, Jan, Boucher, C., Gomez-Lopez, A., Van Wijngaerden, E., Van Ranst, M., Vercauteren, J., Vandamme, A. M., Van Laethem, K., Kostrikis, Leontios G. [0000-0002-5340-7109], López-Galíndez, Cecilio, Erasmus MC other, and Virology
Subjects: Male, Epidemiology, Human immunodeficiency virus type 1 subtype B, Drug Resistance, Human immunodeficiency virus 1, Proteinase Inhibitor, Anti-Hiv Agents, HIV Infections, Men Who Have Sex With Men, Men who have sex with men, Immunodeficiency Viruses, Belgium, Pregnancy, Salud pública, Trend Study, Medicine, Epidemias, Phylogeny, education.field_of_study, Health Survey, 3. Good health, Transmitted Drug Resistance, Medical Microbiology, HIV epidemiology, Viral Pathogens, Cohort, Infection, Viral load, Human, medicine.medical_specialty, Genotype, Science, HIV prevention, Epidemic, Microbial Sensitivity Tests, Disease Surveillance, Microbiology, Article, SDG 3 - Good Health and Well-being, Genetics, Humans, Transmission, Risk factor, education, Microbial Pathogens, Retrospective Studies, Aged, Medicine and health sciences, Preventive medicine, Biology and Life Sciences, Public and occupational health, Immunology, Virus 1 Infection, HIV-1, Viral Diseases, Anti Human Immunodeficiency Virus Agent, Drug resistance, 1 Subtype B, Risk Factors, Prevalence, Cluster Analysis, Public Health Surveillance, Virus Transmission, Viral, Univariate analysis, Multidisciplinary, Microbial Sensitivity Test, Hiv Infections, HIV diagnosis and management, Middle Aged, Infectious Diseases, young adult, Female, Sequence Analysis, Cohort Analysis, Research Article, Antiviral Resistance, Adult, Rna Directed Dna Polymerase Inhibitor, Anti-HIV Agents, Disease Association, Population, Major Clinical Study, Drug Effects, Resistencia a medicamentos, Young Adult, Retrospective Study, Internal medicine, Immunodeficiency Virus Type, Virology, Drug Resistance, Viral, business.industry, Risk Factor, HIV, Gender, Human immunodeficiency virus 1 infection, Confidence interval, Diagnostic medicine, Virus Load, business, Prediction
Abstract: We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (CI): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures. ispartof: PLoS One vol:9 issue:7 ispartof: location:United States status: published
Published: 2014

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

Author: Moutschen, M., Frentz, D., Wensing, A. M. J., Albert, Jan, Paraskevis, Dimitrios N., Abecasis, A. B., Hamouda, O., Jørgensen, L. B., Kücherer, C., Struck, D., Schmit, J. -C, Åsjö, Birgitta, Balotta, Claudia, Beshkov, Danail, Camacho, Ricardo J., Clotet, B., Coughlan, S., De Wit, S., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, Leontios G., Liitsola, K., Linka, M., Nielsen, C., Otelea, D., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Sönnerborg, A., Stanekova, D., Stanojevic, M., Vandamme, A. -M, Boucher, C. A. B., Van de Vijver, D. A. M. C., Balluch, G., Vercauteren, J., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Vandekerckhove, L. P. R., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Van Laethem, K., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Bruckova, M., Machala, L., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Salminen, M., Ristola, M., Suni, J., Sutinen, J., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Chilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., O'Dea, S., Hall, W., Levi, I., Chemtob, D., Franzetti, M., Lai, A., Binda, F., Tramuto, F., Ciccozzi, M., Mussini, C., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Kessel, A., van Bentum, P. H. M., Brinkman, K., de Coul, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., Schuurman, R., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paixão, T., Duque, V., Araújo, F., Jevtovic, D., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Lunar, M., Babic, Dunja Z., Tomazic, J., Vidmar, L., Vovko, T., Karner, P., Domingo, P., Galindo, M. J., Miralles, C., del Pozo, M. A., Ribera, E., Iribarren, J. A., Ruiz, L., de la Torre, J., Vidal, F., Garcia, F., Heidarian, A., Aperia-Peipke, K., Axelsson, M., Mild, M., Karlsson, A., Thalme, A., Navér, L., Bratt, G., Blaxhult, A., Gisslén, M., Svennerholm, B., Bergbrant, I., Björkman, Per, Säll, C., Mellgren, Å., Lindholm, A., Kuylenstierna, N., Montelius, R., Azimi, F., Johansson, B., Carlsson, M., Johansson, E., Ljungberg, B., Ekvall, H., Strand, A., Mäkitalo, S., öberg, S., Holmblad, P., Höfer, M., Holmberg, H., Josefson, P., Ryding, U., Van Kessel, A., Instituto de Higiene e Medicina Tropical (IHMT), Centro de Malária e outras Doenças Tropicais (CMDT), Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Frentz, D, Wensing, AMJ, Albert, J, Paraskevis, D, Abecasis, AB, Hamouda, O, Jørgensen, LB, Kücherer, C, Struck, D, Schmit, JC, Åsjö, B, Balotta, C, Beshkov, D, Camacho, RJ, Clotet, B, Coughlan, S, De Wit, S, Griskevicius, A, Grossman, Z, Horban, A, Kolupajeva, T, Korn, K, Kostrikis, LG, Liitsola, K, Linka, M, Nielsen, C, Otelea, D, Paredes, R, Poljak, M, Puchhammer-Stöckl, E, Sönnerborg, A, Stanekova, D, Stanojevic, M, Vandamme, AM, Boucher, CAB, Van de Vijver, DAMC, Tramuto, F, Van Wijngaerden, Eric, Van Ranst, Marc, Van Laethem, Kristel, Derdelinckx, Inge, Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], Virology, and Graduate School
Subjects: Male, Epidemiology, Human immunodeficiency virus (HIV), Human immunodeficiency virus 1, HIV Infections, medicine.disease_cause, Virologie générale, phylogeny, Settore MED/42 - Igiene Generale E Applicata, Men who have sex with men, EMERGENCE, 0302 clinical medicine, Medicine and Health Sciences, Medicine, Infection control, Cluster Analysis, 030212 general & internal medicine, Israel, Pathologie maladies infectieuses, travel, Phylogeny, 0303 health sciences, Molecular Epidemiology, Travel, Transmission (medicine), article, virus transmission, IMMUNODEFICIENCY-VIRUS TYPE-1, 3. Good health, Europe, female, Infectious Diseases, SUBTYPE B, DRUG-RESISTANT HIV-1, RNA, Viral, male homosexual, Adult, structural gene, Molecular Sequence Data, Newly diagnosed, Clusters, 03 medical and health sciences, male, SDG 3 - Good Health and Well-being, MOLECULAR EPIDEMIOLOGY, SWITZERLAND, Virology, geographic distribution, Humans, Transmission, In patient, human, 030304 developmental biology, nonhuman, Molecular epidemiology, business.industry, Research, high risk population, Virologie médicale, nucleotide sequence, Sequence Analysis, DNA, Human immunodeficiency virus 1 infection, major clinical study, unindexed sequence, 3121 General medicine, internal medicine and other clinical medicine, HIV-1, business, Europe, HIV-1, Transmission, Clusters, Demography, cluster analysis
Abstract: Background: International travel plays a role in the spread of HIV-1 across Europe. It is, however, not known whether international travel is more important for spread of the epidemic as compared to endogenous infections within single countries. In this study, phylogenetic associations among HIV of newly diagnosed patients were determined across Europe.Results: Data came from the SPREAD programme which collects samples of newly diagnosed patients that are representative for national HIV epidemics. 4260 pol sequences from 25 European countries and Israel collected in 2002-2007 were included.We identified 457 clusters including 1330 persons (31.2% of all patients). The cluster size ranged between 2 and 28. A number of 987 patients (74.2%) were part of a cluster that consisted only of patients originating from the same country. In addition, 135 patients (10.2%) were in a cluster including only individuals from neighboring countries. Finally, 208 patients (15.6%) clustered with individuals from countries without a common border. Clustering with patients from the same country was less prevalent in patients being infected with B subtype (P-value, SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2013

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

Author: Moutschen, M., Theys, K., Deforche, K., Vercauteren, J., Libin, P., van de Vijver, D. A. M. C., Albert, Jan, Åsjö, Birgitta, Balotta, Claudia, Bruckova, M., Camacho, Ricardo J., Clotet, B., Coughlan, S., Grossman, Z., Hamouda, O., Horban, A., Korn, K., Kostrikis, Leontios G., Kücherer, C., Nielsen, C., Paraskevis, Dimitrios N., Poljak, M., Puchhammer-Stockl, E., Riva, C., Ruiz, L., Liitsola, K., Schmit, J. -C, Schuurman, R., Sönnerborg, A., Stanekova, D., Stanojevic, M., Struck, D., Van Laethem, K., Wensing, A. M. J., Boucher, C. A. B., Vandamme, A. M., Sarcletti, M., Schmied, B., Geit, M., Balluch, G., Derdelinckx, I., Sasse, A., Bogaert, M., Ceunen, H., De Roo, A., De Wit, S., Echahidi, F., Fransen, K., Goffard, J. -C, Goubau, P., Goudeseune, E., Yombi, J. -C, Lacor, P., Liesnard, C., Pierard, D., Rens, R., Schrooten, Y., Vaira, D., Van den Heuvel, A., Van Der Gucht, B., Van Ranst, M., Van Wijngaerden, E., Vandercam, B., Vekemans, M., Verhofstede, C., Clumeck, N., Demetriades, Ioannis, Kousiappa, Ioanna, Demetriou, Victoria L., Hezka, Johana, Linka, M., Machala, L., Jrgensen, L. B., Gerstoft, J., Mathiesen, L., Pedersen, C., Nielsen, H., Laursen, A., Kvinesdal, B., Ristola, M., Suni, J., Sutinen, J., K̈ucherer, C., Berg, T., Braun, P., Poggensee, G., Däumer, M., Eberle, J., Heiken, H., Kaiser, R., Knechten, H., Müller, H., Neifer, S., Schmidt, B., Walter, H., Gunsenheimer-Bartmeyer, B., Harrer, T., Hatzakis, Angelos E., Magiorkinis, Emmanouil N., Hatzitheodorou, Eleni, Issaris, C., Haida, Catherine, Zavitsanou, Assimina, Magiorkinis, Gkikas, Lazanas, Marios C., Chini, Maria C., Magafas, N., Tsogas, Nickolaos, Paparizos, Vassilios A., Kourkounti, Sofia, Antoniadou, Anastasia C., Papadopoulos, Antonios I., Panagopoulos, Periklis, Poulakou, Garyphallia G., Sakka, V., Chryssos, Georgios, Drimis, Stylianos, Gargalianos, Panagiotis, Lelekis, Moyssis I., Xilomenos, G., Psichogiou, Mina A., Daikos, George L., Panos, George, Haratsis, G., Kordossis, Theodore, Kontos, Athanasios N., Koratzanis, Georgios, Theodoridou, Maria C., Mostrou, Glykeria J., Spoulou, Vana I., Hall, W., De Gascun, C., Byrne, C., Duffy, M., Bergin, C., Reidy, D., Farrell, G., Lambert, J., O'Connor, E., Rochford, A., Low, J., Coakely, P., Levi, I., Chemtob, D., Mussini, C., Caramma, I., Capetti, A., Colombo, M. C., Rossi, C., Prati, F., Tramuto, F., Vitale, F., Ciccozzi, M., Angarano, G., Rezza, G., Schmit, J. C., Hemmer, R., Arendt, V., Staub, T., Schneider, F., Roman, F., van Bentum, P. H. M., Brinkman, K., op de Coul, E. L., van der Ende, M. E., Hoepelman, I. M., van Kasteren, M., Juttmann, J., Kuipers, M., Langebeek, N., Richter, C., Santegoets, R. M. W. J., Schrijnders-Gudde, L., van de Ven, B. J. M., Ormaasen, V., Aavitsland, P., Stanczak, J. J., Stanczak, G. P., Firlag-Burkacka, E., Wiercinska-Drapalo, A., Jablonowska, E., Malolepsza, E., Leszczyszyn-Pynka, M., Szata, W., Palma, C., Borges, F., Paix̃ao, T., Duque, V., Araújo, F., Jevtovic, D. J., Salemovic, D., Habekova, M., Mokráš, Miloš, Truska, P., Babic, Dunja Z., Tomazic, J., Vidmar, L., Karner, P., Gutíerrez, C., deMendoza, C., Erkicia, I., Domingo, P., Camino, X., Galindo, M. J., Blanco, J. L., Leal, M., Masabeu, A., Guelar, A., Llibre, J. M., Margall, N., Iribarren, J. A., Gutierrez, S., Baldov́i, J. F., Pedreira, J. D., Gatell, J. M., Moreno, S., de Mendoza, C., Soriano, V., Blaxhult, A., Heidarian, A., Karlsson, A., Aperia-Peipke, K., Bergbrant, I. -M, Gissĺen, M., Svennerholm, M., Björkman, Per, Bratt, G., Carlsson, M., Ekvall, H., Ericsson, M., Ḧofer, M., Johansson, B., Sonnerb̈org, A., Kuylenstierna, N., Ljungberg, B., Mäkitalo, S., Strand, A., Öberg, S., Virology, Erasmus MC other, Van Wijngaerden, Eric, Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Centro de Malária e outras Doenças Tropicais (CMDT), Graduate School, Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], UCL - SSS/IREC/MBLG - Pôle de Microbiologie médicale, UCL - (SLuc) Service de microbiologie, UCL - (SLuc) Service de médecine interne générale, Theys, K, Deforche, K, Vercauteren, J, Libin, P, van de Vijver, DA, Albert, J, Asjö, B, Balotta, C, Bruckova, M, Camacho, RJ, Clotet, B, Coughlan, S, Grossman, Z, Hamouda, O, Horban, A, Korn, K, Kostrikis, LG, Kücherer, C, Nielsen, C, Paraskevis, D, Poljak, M, Puchhammer Stockl, E, Riva, C, Ruiz, L, Liitsola, K, Schmit, JC, Schuurman, R, Sönnerborg, A, Stanekova, D, Stanojevic, M, Struck, D, Van Laethem, K, Wensing, AM, Boucher, CA, Vandamme, AM, Tramuto, F, and Vitale, F
Subjects: Adult, Male, lcsh:Immunologic diseases. Allergy, Anti-HIV Agents, education, Virulence, HIV Infections, Drug resistance, Biology, Settore MED/42 - Igiene Generale E Applicata, Virus, polymorphism, 03 medical and health sciences, Viral Proteins, SDG 3 - Good Health and Well-being, Virology, Genotype, Drug Resistance, Viral, drug-naive, medicine, Humans, Prospective Studies, 030304 developmental biology, 0303 health sciences, Polymorphism, Genetic, 030306 microbiology, Research, protease, Viral Load, Reverse transcriptase, 3. Good health, CD4 Lymphocyte Count, Drug-naïve, Infectious Diseases, 3121 General medicine, internal medicine and other clinical medicine, Immunology, biology.protein, HIV-1, Female, Antibody, lcsh:RC581-607, Viral load, HIV-1 infected patient, medicine.drug, Peptide Hydrolases
Abstract: Background: The effect of drug resistance transmission on disease progression in the newly infected patient is not well understood. Major drug resistance mutations severely impair viral fitness in a drug free environment, and therefore expected to revert quickly. Compensatory mutations, often already polymorphic in wild-type viruses, do not tend to revert after transmission. While compensatory mutations increase fitness during treatment, their presence may also modulate viral fitness and virulence in absence of therapy and major resistance mutations. We previously designed a modeling technique that quantifies genotypic footprints of in vivo treatment selective pressure, including both drug resistance mutations and polymorphic compensatory mutations, through the quantitative description of a fitness landscape from virus genetic sequences. Results: Genotypic correlates of viral load and CD4 cell count were evaluated in subtype B sequences from recently diagnosed treatment-naive patients enrolled in the SPREAD programme. The association of surveillance drug resistance mutations, reported compensatory mutations and fitness estimated from drug selective pressure fitness landscapes with baseline viral load and CD4 cell count was evaluated using regression techniques. Protease genotypic variability estimated to increase fitness during treatment was associated with higher viral load and lower CD4 cell counts also in treatment-naive patients, which could primarily be attributed to well-known compensatory mutations at highly polymorphic positions. By contrast, treatment-related mutations in reverse transcriptase could not explain viral load or CD4 cell count variability. Conclusions: These results suggest that polymorphic compensatory mutations in protease, reported to be selected during treatment, may improve the replicative capacity of HIV-1 even in absence of drug selective pressure or major resistance mutations. The presence of this polymorphic variation may either reflect a history of drug selective pressure, i.e. transmission from a treated patient, or merely be a result of diversity in wild-type virus. Our findings suggest that transmitted drug resistance has the potential to contribute to faster disease progression in the newly infected host and to shape the HIV-1 epidemic at a population level. ispartof: Retrovirology vol:9 issue:1 ispartof: location:England status: published
Published: 2012

17. Trends and Predictors of Transmitted Drug Resistance (TDR) and Clusters with TDR in a Local Belgian HIV-1 Epidemic

Author: Pineda-Pena, AC, Schrooten, Y, Vinken, L, Ferreira, F, Li, GD, Trovao, NS, Khouri, R, Derdelinckx, I, De Munter, P, Kucherer, C, Kostrikis, LG, Nielsen, C, Littsola, K, Wensing, A, Stanojevic, M, Paredes, R, Balotta, C, Albert, J (Jan), Boucher, Charles, Gomez-Lopez, A, van Wijngaerden, E, van Ranst, M, Vercauteren, J, Vandamme, AM, Van Laethem, K, Pineda-Pena, AC, Schrooten, Y, Vinken, L, Ferreira, F, Li, GD, Trovao, NS, Khouri, R, Derdelinckx, I, De Munter, P, Kucherer, C, Kostrikis, LG, Nielsen, C, Littsola, K, Wensing, A, Stanojevic, M, Paredes, R, Balotta, C, Albert, J (Jan), Boucher, Charles, Gomez-Lopez, A, van Wijngaerden, E, van Ranst, M, Vercauteren, J, Vandamme, AM, and Van Laethem, K
Abstract: We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (Cl): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures.
Published: 2014

18. High frequency of antiviral drug resistance and non-b subtypes in HIV-1 patients failing antiviral therapy in Cuba

Author: Kouri V, Alemán Y, Pérez L, Pérez J, Fonseca C, Correa C, Aragonés C, Campos J, Álvarez D, Schrooten Y, Vinken L, Limia C, Soto Y, Anne-Mieke Vandamme, and Van Laethem K

19. In vitro resistance development of human immunodeficiency virus type 1 towards mannose-specific plant lectins

Author: Laethem, K., Schrooten, Y., Hatse, S., Kurt Vermeire, Clercq, E., Peumans, W., Damme, E., Schols, D., Vandamme, Am, and Balzarini, J.

20. Drug resistance among therapy-naive HIV-infected patients studied by sequencing and VERSANT (TM) HIV-1 resistance assays (LiPA) has limited impact on treatment response

Author: Derdelinckx, I., Laethem, K., Maes, B., Schrooten, Y., Dewit, S., Florence, E., Fransen, K., Ribas, Sg, Marissens, D., Moutschen, M., Wijngaerden, E., Vaira, D., Zissis, G., Ranst, M., and Anne-Mieke Vandamme

21. Phylogenetic Analysis of Hepatitis C Virus Infections in a Large Belgian Cohort Using Next-Generation Sequencing of Full-Length Genomes.

Author: Christensen KT, Pierard F, Bonsall D, Bowden R, Barnes E, Florence E, Ansari MA, Nguyen D, de Cesare M, Nevens F, Robaeys G, Schrooten Y, Busschots D, Simmonds P, Vandamme AM, Van Wijngaerden E, Dierckx T, Cuypers L, and Van Laethem K
Subjects: Male, Humans, Hepacivirus genetics, Phylogeny, Homosexuality, Male, Belgium epidemiology, High-Throughput Nucleotide Sequencing, Substance Abuse, Intravenous complications, HIV Infections, Sexual and Gender Minorities, Hepatitis C, HIV Seropositivity
Abstract: The hepatitis C virus (HCV) epidemic in Western countries is primarily perpetuated by the sub-populations of men who have sex with men (MSM) and people who inject drugs (PWID). Understanding the dynamics of transmission in these communities is crucial for removing the remaining hurdles towards HCV elimination. We sequenced 269 annotated HCV plasma samples using probe enrichment and next-generation sequencing, obtaining 224 open reading frames of HCV (OR497849-OR498072). Maximum likelihood phylogenies were generated on the four most prevalent subtypes in this study (HCV1a, 1b, 3a, 4d) with a subsequent transmission cluster analysis. The highest rate of clustering was observed for HCV4d samples (13/17 (76.47%)). The second highest rate of clustering was observed in HCV1a samples (42/78 (53.85%)) with significant association with HIV-positive MSM. HCV1b and HCV3a had very low rates of clustering (2/83 (2.41%) and (0/29)). The spread of the prevalent subtype HCV1b appears to have been largely curtailed, and we demonstrate the onwards transmission of HCV1a and HCV4d in the HIV-positive MSM population across municipal borders. More systematic data collection and sequencing is needed to allow a better understanding of the HCV transmission among the community of PWID and overcome the remaining barriers for HCV elimination in Belgium.
Published: 2023
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22. Full-genome next-generation sequencing of hepatitis C virus to assess the accuracy of genotyping by the commercial assay LiPA and the prevalence of resistance-associated substitutions in a Belgian cohort.

Author: Christensen KT, Pierard F, Beuselinck K, Bonsall D, Bowden R, Lagrou K, Nevens F, Schrooten Y, Simmonds P, Vandamme AM, Van Wijngaerden E, Dierckx T, Cuypers L, and Van Laethem K
Subjects: Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Belgium epidemiology, Drug Resistance, Viral genetics, Genotype, Hepacivirus genetics, High-Throughput Nucleotide Sequencing methods, Humans, Prevalence, Viral Nonstructural Proteins genetics, Hepatitis C drug therapy, Hepatitis C epidemiology, Hepatitis C, Chronic drug therapy
Abstract: Background: Although most currently used regimens for Hepatitis C virus (HCV) infections can be initiated without prior knowledge of genotype and subtype, genotyping is still useful to identify patients who might benefit from a personalized treatment due to resistance to direct-acting antivirals (DAA)., Objectives: To assess the utility of full-genome next-generation sequencing (FG-NGS) for HCV genotyping., Study Design: 138 HCV plasma samples previously genotyped by VERSANT HCV Genotype Assay (LiPA) were subjected to FG-NGS and phylogenetically genotyped Genome Detective. Consensuses were analysed by HCV-GLUE for resistance-associated substitutions (RASs) and their impact on treatment response was investigated., Results: 102/138 (73.9%) samples were sequenced to a genome coverage and depth of >90% of the HCV open reading frame covered by >100 reads/site. Concordant genotype and subtype results were assigned in 97.1% and 79.4% of samples, respectively. FG-NGS resolved the subtype of 13.7% samples that had ambiguous calls by LiPA and identified one dual infection and one recombinant strain. At least one RAS was found for the HCV genes NS3, NS5A, and NS5B in 2.91%, 36.98% and 27.3% samples, respectively. Irrespective of the observed RAS, all patients responded well to DAA treatment, except for HCV1b-infected patients treated with Zepatier (33.3% failure rate (5/15))., Conclusion: While LiPA and FG-NGS showed overall good concordance, FG-NGS improved specificity for subtypes, recombinant and mixed infections. FG-NGS enabled the detection of RAS, but its predictive value for treatment outcome in DAA-naïve patients remains uncertain. With additional refinements, FG-NGS may be the way forward for HCV genotyping., Competing Interests: Declaration of Competing Interest The authors declare no commercial or financial relationship that could be construed as potential conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)
Published: 2022
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23. Exploring resistance pathways for first-generation NS3/4A protease inhibitors boceprevir and telaprevir using Bayesian network learning.

Author: Cuypers L, Libin P, Schrooten Y, Theys K, Di Maio VC, Cento V, Lunar MM, Nevens F, Poljak M, Ceccherini-Silberstein F, Nowé A, Van Laethem K, and Vandamme AM
Subjects: Amino Acid Substitution, Antiviral Agents therapeutic use, Bayes Theorem, Cohort Studies, Databases, Genetic, Europe epidemiology, Female, Genotype, Hepacivirus classification, Hepacivirus drug effects, Hepacivirus isolation & purification, Hepatitis C, Chronic epidemiology, Hepatitis C, Chronic virology, Humans, Intracellular Signaling Peptides and Proteins, Male, Middle Aged, Mutation, Missense, Proline therapeutic use, Protease Inhibitors therapeutic use, RNA, Viral genetics, Carrier Proteins genetics, Drug Resistance, Viral genetics, Hepacivirus genetics, Hepatitis C, Chronic drug therapy, Oligopeptides therapeutic use, Proline analogs & derivatives, Viral Nonstructural Proteins genetics
Abstract: Resistance-associated variants (RAVs) have been shown to influence treatment response to direct-acting antivirals (DAAs) and first generation NS3/4A protease inhibitors (PIs) in particular. Interpretation of hepatitis C virus (HCV) genotypic drug resistance remains a challenge, especially in patients who previously failed DAA therapy and need to be retreated with a second DAA based regimen. Bayesian network (BN) learning on HCV sequence data from patients treated with DAAs could provide insight in resistance pathways against PIs for HCV subtypes 1a and 1b, in a similar way as applied before for HIV. The publicly available 'Rega-BN' tool chain was developed to study associative analyses for various pathogens. Our first analysis, comparing sequences from PI-naïve and PI-experienced patients, determined that NS3 substitutions R155K and V36M arise with PI-exposure in HCV1a infected patients, and were defined as major and minor resistance-associated variants respectively. NS3 variant 174H was newly identified as potentially related to PI resistance. In a second analysis, NS3 sequences from PI-naïve patients who cleared the virus during PI therapy and from PI-naïve patients who failed PI therapy were compared, showing that NS3 baseline variant 67S predisposes to treatment-failure and variant 72I to treatment success. This approach has the potential to better characterize the role of more RAVs, if sufficient therapy annotated sequence data becomes available in curated public databases. In addition, polymorphisms present in baseline sequences that predispose patients to therapy failure can be identified using this approach., (Copyright © 2017 Elsevier B.V. All rights reserved.)
Published: 2017
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24. Implications of hepatitis C virus subtype 1a migration patterns for virus genetic sequencing policies in Italy.

Author: Cuypers L, Vrancken B, Fabeni L, Marascio N, Cento V, Di Maio VC, Aragri M, Pineda-Peña AC, Schrooten Y, Van Laethem K, Balog D, Focà A, Torti C, Nevens F, Perno CF, Vandamme AM, and Ceccherini-Silberstein F
Subjects: Antiviral Agents pharmacology, Bayes Theorem, Drug Resistance, Viral, Genotype, Hepacivirus drug effects, Hepacivirus genetics, Hepatitis C epidemiology, Humans, Italy epidemiology, Simeprevir pharmacology, Hepacivirus physiology, Hepatitis C virology
Abstract: Background: In-depth phylogeographic analysis can reveal migration patterns relevant for public health planning. Here, as a model, we focused on the provenance, in the current Italian HCV subtype 1a epidemic, of the NS3 resistance-associated variant (RAV) Q80K, known to interfere with the action of NS3/4A protease inhibitor simeprevir. HCV1a migration patterns were analysed using Bayesian phylodynamic tools, capitalising on newly generated and publicly available time and geo-referenced NS3 encoding virus genetic sequence data., Results: Our results showed that both immigration and local circulation fuel the current Italian HCV1a epidemic. The United States and European continental lineages dominate import into Italy, with the latter taking the lead from the 1970s onwards. Since similar migration patterns were found for Q80K and other lineages, no clear differentiation of the risk for failing simeprevir can be made between patients based on their migration and travel history. Importantly, since HCV only occasionally recombines, these results are readily transferable to the genetic sequencing policy concerning NS5A RAVs., Conclusions: The patient migration and travel history cannot be used to target only part of the HCV1a infected population for drug resistance testing before start of antiviral therapy. Consequently, it may be cost-effective to expand genotyping efforts to all HCV1a infected patients eligible for simeprevir-based therapies.
Published: 2017
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25. 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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26. Performance of an in-house human immunodeficiency virus type 1 genotyping system for assessment of drug resistance in Cuba.

Author: Alemán Y, Vinken L, Kourí V, Pérez L, Álvarez A, Abrahantes Y, Fonseca C, Pérez J, Correa C, Soto Y, Schrooten Y, Vandamme AM, and Van Laethem K
Subjects: Cuba, HIV Protease Inhibitors pharmacology, Humans, Reproducibility of Results, Reverse Transcriptase Inhibitors pharmacology, Drug Resistance, Viral genetics, Genotyping Techniques, HIV-1 drug effects, HIV-1 genetics
Abstract: As commercial human immunodeficiency virus type 1 drug resistance assays are expensive, they are not commonly used in resource-limited settings. Hence, a more affordable in-house procedure was set up taking into account the specific epidemiological and economic circumstances of Cuba. The performance characteristics of the in-house assay were evaluated using clinical samples with various subtypes and resistance patterns. The lower limit of amplification was determined on dilutions series of 20 clinical isolates and ranged from 84 to 529 RNA copies/mL. For the assessment of trueness, 14 clinical samples were analyzed and the ViroSeq HIV-1 Genotyping System v2.0 was used as the reference standard. The mean nucleotide sequence identity between the two assays was 98.7% ± 1.0. Additionally, 99.0% of the amino acids at drug resistance positions were identical. The sensitivity and specificity in detecting drug resistance mutations was respectively 94.1% and 99.5%. Only few discordances in drug resistance interpretation patterns were observed. The repeatability and reproducibility were evaluated using 10 clinical samples with 3 replicates per sample. The in-house test was very precise as nucleotide sequence identity among paired nucleotide sequences ranged from 98.7% to 99.9%. The acceptance criteria were met by the in-house test for all performance characteristics, demonstrating a high degree of accuracy. Subsequently, the applicability in routine clinical practice was evaluated on 380 plasma samples. The amplification success rate was 91% and good quality consensus sequences encoding the entire protease and the first 335 codons in reverse transcriptase could be obtained for 99% of the successful amplicons. The reagent cost per sample using the in-house procedure was around € 80 per genotyping attempt. Overall, the in-house assay provided good results, was feasible with equipment and reagents available in Cuba and was half as expensive as commercial assays.
Published: 2015
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27. High frequency of antiviral drug resistance and non-b subtypes in HIV-1 patients failing antiviral therapy in Cuba.

Author: Kouri V, Alemán Y, Pérez L, Pérez J, Fonseca C, Correa C, Aragonés C, Campos J, Alvarez D, Schrooten Y, Vinken L, Limia C, Soto Y, Vandamme AM, and Van Laethem K
Abstract: Introduction: Emergence of HIV-1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART) in settings with limited laboratory monitoring and drug options. The objective is to implement the surveillance of drug resistance and subtypes in HIV-1 patients failing ART in Cuba., Methods: This study compiled clinical and genotypic drug resistance data 588 ART-experienced HIV-1 patients attending a clinical center in Havana in 2009-2013. Drug resistance testing was performed as part of routine clinical care. Drug resistance mutations and levels were determined using Rega version 8.0.2., Results: Eighty-three percent received solely ART containing at least three drugs. Patients from 2009 to 2010 were longer treated (median: 4.9 vs 2.7 years) and exposed to more ART regimens (median: 4 vs 2 regimens) compared to patients from 2011-2013. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside RTI (NNRTI) and PI mutations were present in 83.5, 77.4 and 52.0%. Full-class resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR) were detected in 25.0, 33.7, 11.4 and 6.3%. FCR to NRTI, NNRTI, PI and MDR were present in 12.8, 28.7, 0 and 0% after first-line failure (164 patients) and in 23.1, 34.6, 3.8 and 3.1% after second-line failure (130 patients). Subtype B (32.5%), BG recombinants (19.6%) and CRF19_cpx (16.2%) were the most prevalent genetic forms. Subtype distribution did not change significantly between 2009-2010 and 2011-2013, except for BG recombinants that increased from 12.2 to 21.3% (p=0.002)., Conclusions: Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure.
Published: 2014
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28. Trends and predictors of transmitted drug resistance (TDR) and clusters with TDR in a local Belgian HIV-1 epidemic.

Author: Pineda-Peña AC, Schrooten Y, Vinken L, Ferreira F, Li G, Trovão NS, Khouri R, Derdelinckx I, De Munter P, Kücherer C, Kostrikis LG, Nielsen C, Littsola K, Wensing A, Stanojevic M, Paredes R, Balotta C, Albert J, Boucher C, Gomez-Lopez A, Van Wijngaerden E, Van Ranst M, Vercauteren J, Vandamme AM, and Van Laethem K
Subjects: Adult, Aged, Anti-HIV Agents pharmacology, Anti-HIV Agents therapeutic use, Belgium epidemiology, Cluster Analysis, Female, Genotype, HIV Infections drug therapy, HIV Infections transmission, HIV-1 drug effects, Humans, Male, Microbial Sensitivity Tests, Middle Aged, Pregnancy, Prevalence, Public Health Surveillance, Retrospective Studies, Risk Factors, Young Adult, Drug Resistance, Viral genetics, HIV Infections epidemiology, HIV Infections virology, HIV-1 genetics
Abstract: We aimed to study epidemic trends and predictors for transmitted drug resistance (TDR) in our region, its clinical impact and its association with transmission clusters. We included 778 patients from the AIDS Reference Center in Leuven (Belgium) diagnosed from 1998 to 2012. Resistance testing was performed using population-based sequencing and TDR was estimated using the WHO-2009 surveillance list. Phylogenetic analysis was performed using maximum likelihood and Bayesian techniques. The cohort was predominantly Belgian (58.4%), men who have sex with men (MSM) (42.8%), and chronically infected (86.5%). The overall TDR prevalence was 9.6% (95% confidence interval (CI): 7.7-11.9), 6.5% (CI: 5.0-8.5) for nucleoside reverse transcriptase inhibitors (NRTI), 2.2% (CI: 1.4-3.5) for non-NRTI (NNRTI), and 2.2% (CI: 1.4-3.5) for protease inhibitors. A significant parabolic trend of NNRTI-TDR was found (p = 0.019). Factors significantly associated with TDR in univariate analysis were male gender, Belgian origin, MSM, recent infection, transmission clusters and subtype B, while multivariate and Bayesian network analysis singled out subtype B as the most predictive factor of TDR. Subtype B was related with transmission clusters with TDR that included 42.6% of the TDR patients. Thanks to resistance testing, 83% of the patients with TDR who started therapy had undetectable viral load whereas half of the patients would likely have received a suboptimal therapy without this test. In conclusion, TDR remained stable and a NNRTI up-and-down trend was observed. While the presence of clusters with TDR is worrying, we could not identify an independent, non-sequence based predictor for TDR or transmission clusters with TDR that could help with guidelines or public health measures.
Published: 2014
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29. Horizontal gene transfer from human host to HIV-1 reverse transcriptase confers drug resistance and partly compensates for replication deficits.

Author: Megens S, Vaira D, De Baets G, Dekeersmaeker N, Schrooten Y, Li G, Schymkowitz J, Rousseau F, Vandamme AM, Moutschen M, and Van Laethem K
Subjects: Chromosomes, Human, HIV Infections virology, HIV-1 drug effects, HIV-1 isolation & purification, HIV-1 physiology, Humans, Models, Molecular, Molecular Sequence Data, Mutagenesis, Insertional, Phylogeny, Protein Conformation, RNA, Viral genetics, Sequence Analysis, DNA, Sequence Homology, Drug Resistance, Viral, Gene Transfer, Horizontal, HIV Reverse Transcriptase genetics, HIV-1 enzymology, HIV-1 genetics, Virus Replication
Abstract: We investigated the origin and the effect of insertion D67D-THGERDLGPA within HIV-1 RT from a patient failing antiviral therapy. The insertion developed within the context of pre-existing NRTI and NNRTI mutations (M41L, L210W, T215Y and N348I). Concurrently, the NRTI mutations T69I and V118I and the NNRTI mutations K103N and Y181C were detected for the first time. High-level drug resistance (fold-changes≥50) and a good replication capacity (87% of wild-type) were observed, significantly higher than for the previous virus without insertion. The insertion was very similar to a region within human chromosome 17 (31/34 nucleotide identity), and had already been detected independently in a Japanese HIV-1 isolate. These results suggest that a particular sequence within human chromosome 17 is prone to horizontal gene transfer into the HIV-1 RT finger subdomain. This insertion confers selective advantage to HIV-1 by its contribution to multi-drug resistance and restoration of impaired replication capacity., (Copyright © 2014 Elsevier Inc. All rights reserved.)
Published: 2014
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30. Evaluation of the automatic editing tool RECall for HIV-1 pol and V3 loop sequences.

Author: Vinken L, Megens S, Schrooten Y, Vandamme AM, and Van Laethem K
Subjects: Humans, Microbial Sensitivity Tests methods, Automation, Laboratory methods, Computational Biology methods, HIV-1 genetics, Sequence Analysis, DNA
Abstract: Genotypic drug resistance testing is routine practice in HIV-1 clinical care. The visual interpretation of sequencing electropherograms is labour-intensive and subject to intra- and inter-assay variability because decisions are based on operators' judgments. In this study the performance of the automatic editing tool RECall was compared to the current standard of editing manually and editing using the tool ViroSeq. Using RECall a consensus sequence could be generated for 97% of the V3 loop and for 79% of the pol experiments. By comparison, using manual editing a consensus sequence could be reached for 87% of the V3 and 87% of the pol experiments. Using ViroSeq, a consensus sequence was generated for 68% of the pol experiments. On a predefined dataset, manual editing displayed the highest probability to accurately assign mixtures (0.91 vs. 0.88 by ViroSeq vs. 0.76 by RECall) and the lowest probability to inaccurately assign a mixture to a pure base call (0.002 vs. 0.019 by ViroSeq vs. 0.002 by RECall). As differences in base calling have little impact on drug resistance interpretation and hands-on-time could be substantially reduced, RECall could be a valuable tool for the standardization and acceleration of the editing process., (Copyright © 2013 Elsevier B.V. All rights reserved.)
Published: 2013
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31. Antiretroviral drug resistance in HIV-1 therapy-naive patients in Cuba.

Author: Pérez L, Kourí V, Alemán Y, Abrahantes Y, Correa C, Aragonés C, Martínez O, Pérez J, Fonseca C, Campos J, Álvarez D, Schrooten Y, Dekeersmaeker N, Imbrechts S, Beheydt G, Vinken L, Soto Y, Álvarez A, Vandamme AM, and Van Laethem K
Subjects: Adolescent, Adult, Anti-HIV Agents therapeutic use, Cuba epidemiology, Drug Resistance, Viral, Female, HIV Infections epidemiology, HIV-1 classification, Humans, Male, Middle Aged, Anti-HIV Agents pharmacology, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects
Abstract: In Cuba, antiretroviral therapy rollout started in 2001 and antiretroviral therapy coverage has reached almost 40% since then. The objectives of this study were therefore to analyze subtype distribution, and level and patterns of drug resistance in therapy-naive HIV-1 patients. Four hundred and one plasma samples were collected from HIV-1 therapy-naive patients in 2003 and in 2007-2011. HIV-1 drug resistance genotyping was performed in the pol gene and drug resistance was interpreted according to the WHO surveillance drug-resistance mutations list, version 2009. Potential impact on first-line therapy response was estimated using genotypic drug resistance interpretation systems HIVdb version 6.2.0 and Rega version 8.0.2. Phylogenetic analysis was performed using Neighbor-Joining. The majority of patients were male (84.5%), men who have sex with men (78.1%) and from Havana City (73.6%). Subtype B was the most prevalent subtype (39.3%), followed by CRF20-23-24_BG (19.5%), CRF19_cpx (18.0%) and CRF18_cpx (10.3%). Overall, 29 patients (7.2%) had evidence of drug resistance, with 4.0% (CI 1.6%-4.8%) in 2003 versus 12.5% (CI 7.2%-14.5%) in 2007-2011. A significant increase in drug resistance was observed in recently HIV-1 diagnosed patients, i.e. 14.8% (CI 8.0%-17.0%) in 2007-2011 versus 3.8% (CI 0.9%-4.7%) in 2003 (OR 3.9, CI 1.5-17.0, p=0.02). The majority of drug resistance was restricted to a single drug class (75.8%), with 55.2% patients displaying nucleoside reverse transcriptase inhibitor (NRTI), 10.3% non-NRTI (NNRTI) and 10.3% protease inhibitor (PI) resistance mutations. Respectively, 20.7% and 3.4% patients carried viruses containing drug resistance mutations against NRTI+NNRTI and NRTI+NNRTI+PI. The first cases of resistance towards other drug classes than NRTI were only detected from 2008 onwards. The most frequent resistance mutations were T215Y/rev (44.8%), M41L (31.0%), M184V (17.2%) and K103N (13.8%). The median genotypic susceptibility score for the commonly prescribed first-line therapies was 2.5. This analysis emphasizes the need to perform additional surveillance studies to accurately assess the level of transmitted drug resistance in Cuba, as the extent of drug resistance might jeopardize effectiveness of first-line regimens prescribed in Cuba and might necessitate the implementation of baseline drug resistance testing., (Copyright © 2013 Elsevier B.V. All rights reserved.)
Published: 2013
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32. High frequency of antiviral drug resistance and non-B subtypes in HIV-1 patients failing antiviral therapy in Cuba.

Author: Kourí V, Alemán Y, Pérez L, Pérez J, Fonseca C, Correa C, Aragonés C, Campos J, Álvarez D, Schrooten Y, Dekeersmaeker N, Imbrechts S, Beheydt G, Vinken L, Pérez D, Álvarez A, Soto Y, Vandamme AM, and Van Laethem K
Subjects: Adult, Cuba epidemiology, Female, Genotype, HIV Infections drug therapy, HIV-1 genetics, HIV-1 isolation & purification, Humans, Male, Middle Aged, Molecular Epidemiology, Prevalence, Treatment Failure, Anti-HIV Agents pharmacology, Drug Resistance, Viral, HIV Infections epidemiology, HIV Infections virology, HIV-1 classification, HIV-1 drug effects
Abstract: Background: Emergence of HIV-1 drug resistance may limit the sustained benefits of antiretroviral therapy (ART) in settings with limited laboratory monitoring and drug options., Objectives: Surveillance of drug resistance and subtypes in HIV-1 patients failing ART in Cuba., Study Design: This study compiled data of ART-experienced HIV-1 patients attending a clinical center in Havana in 2003 and 2009-2011. The first period included results of a cross-sectional study, whereas in the second period genotyping was performed as part of routine care. Drug resistance mutations and levels were determined using HIVdb version 6.0.9., Results: Seventy-six percent received solely ART containing at least 3 drugs, of which 79.1% ever receiving unboosted protease inhibitors (PI). Patients from 2009 to 2011 were longer treated and exposed to more ART regimens. Subtype B (39%) and CRF19_cpx (18%) were the most prevalent genetic forms. Subtype distribution did not change significantly between both periods, except for BG recombinants that increased from 6% to 14%. Nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside RTI (NNRTI) and PI mutations were present in 69.5%, 54.8% and 44.4%. Full-class resistance (FCR) to NRTI, NNRTI, PI and multidrug resistance (MDR) were detected in 31.8%, 37.9%, 18.5% and 15.4%. FCR to NRTI, NNRTI, PI and MDR were present in 9.8%, 14.1%, 0%, 0% after first-line failure and in 19.8%, 20.8%, 2.9% and 2.9% after second-line failure., Conclusions: Our study found a high prevalence of drug resistance and supports the need for appropriate laboratory monitoring in clinical practice and access to drug options in case of virological failure., (Copyright © 2012 Elsevier B.V. All rights reserved.)
Published: 2012
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33. Novel recombinant virus assay for measuring susceptibility of human immunodeficiency virus type 1 group M subtypes to clinically approved drugs.

Author: Covens K, Dekeersmaeker N, Schrooten Y, Weber J, Schols D, Quiñones-Mateu ME, Vandamme AM, and Van Laethem K
Subjects: Cell Line, Flow Cytometry, Genes, Reporter, Green Fluorescent Proteins genetics, Green Fluorescent Proteins metabolism, Humans, Microbial Sensitivity Tests methods, Proviruses genetics, Recombination, Genetic, Reproducibility of Results, Sequence Deletion, Anti-HIV Agents pharmacology, HIV-1 drug effects
Abstract: Combination therapy can successfully suppress human immunodeficiency virus (HIV) replication in patients but selects for drug resistance, requiring subsequent resistance-guided therapeutic changes. This report describes the development and validation of a novel assay that offers a uniform method to measure susceptibility to all clinically approved HIV type 1 (HIV-1) drugs targeting reverse transcriptase (RT), protease (PR), integrase (IN), and viral entry. It is an assay in which the antiviral effect on infection within a single replication cycle is measured in triply transfected U87.CD4.CXCR4.CCR5 cells, based on homologous recombination between patient-derived amplicons and molecular proviral clones tagged with the enhanced green fluorescent protein (EGFP) reporter gene and from which certain viral genomic regions are removed. The deletions stretch from p17 codon 7 to PR codon 98 in pNL4.3-DeltagagPR-EGFP, from PR codons 1 to 99 in pNL4.3-DeltaPR-EGFP, from RT codons 1 to 560 in pNL4.3-DeltaRT-EGFP, from IN codons 1 to 288 in pNL4.3-DeltaIN-EGFP, and from gp120 codon 34 to gp41 codon 237 in pNL4.3-Deltaenv-EGFP. The optimized experimental conditions enable the investigation of patient samples regardless of viral subtype or coreceptor use. The extraction and amplification success rate for a set of clinical samples belonging to a broad range of HIV-1 group M genetic forms (A-J, CRF01-03, CRF05, and CRF12-13) and displaying a viral load range of 200 to >500,000 RNA copies/ml was 97%. The drug susceptibility measurements, based on discrimination between infected and noninfected cells on a single-cell level by flow cytometry, were reproducible, with coefficients of variation for resistance ranging from 7% to 31%, and were consistent with scientific literature in terms of magnitude and specificity.
Published: 2009
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34. Evolution of genotypic resistance to enfuvirtide in HIV-1 isolates from different group M subtypes.

Author: Covens K, Kabeya K, Schrooten Y, Dekeersmaeker N, Van Wijngaerden E, Vandamme AM, De Wit S, and Van Laethem K
Subjects: Amino Acid Sequence, Amino Acid Substitution genetics, Enfuvirtide, HIV-1 classification, HIV-1 isolation & purification, Humans, Molecular Sequence Data, Mutation, Missense, Salvage Therapy methods, Sequence Analysis, DNA, Treatment Failure, Anti-HIV Agents pharmacology, Drug Resistance, Viral, Evolution, Molecular, HIV Envelope Protein gp41 genetics, HIV Envelope Protein gp41 pharmacology, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, HIV-1 genetics, Peptide Fragments pharmacology
Abstract: Background: Enfuvirtide is active against isolates from different HIV-1 subtypes. In vitro and in vivo studies reveal that resistance mutations are primarily found within the region spanning amino acid 36-45 of gp41. However, most studies include only subtype B strains, while it is known that especially the env region is very divergent among subtypes., Objectives: To analyze the gp41 HR1 genetic evolution during failure of enfuvirtide-containing salvage regimens in 19 HIV-1 patients infected with strains from different group M subtypes., Study Design: The gp41 sequence was determined at baseline and upon failure in 19 patients. For a subset of 7 patients, samples were available after discontinuation of enfuvirtide., Results: Our results confirmed the conserved nature of the HR1 region. Escape mutants during chronic treatment with enfuvirtide were mainly observed within region 36-45. One novel mutation was identified, i.e. S42G in a subtype A1 strain., Conclusions: Different subtypes escape enfuvirtide selective pressure through similar mutational patterns, however a new S42G variant was observed. The in vivo selection of S42G suggests that it might play a role in enfuvirtide resistance. Therefore, it could be considered as a candidate mutation to be included within drug resistance interpretation systems.
Published: 2009
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35. A genotypic assay for the amplification and sequencing of integrase from diverse HIV-1 group M subtypes.

Author: Van Laethem K, Schrooten Y, Covens K, Dekeersmaeker N, De Munter P, Van Wijngaerden E, Van Ranst M, and Vandamme AM
Subjects: DNA, Complementary, Genotype, HIV Integrase Inhibitors pharmacology, HIV-1 classification, HIV-1 drug effects, HIV-1 genetics, Humans, Microbial Sensitivity Tests, Pyrrolidinones pharmacology, RNA, Viral analysis, RNA, Viral isolation & purification, Raltegravir Potassium, Sequence Analysis, DNA, Drug Resistance, Viral genetics, HIV Integrase genetics, HIV-1 enzymology, Polymerase Chain Reaction methods
Abstract: Recently, the Food and Drug Administration (FDA) of the USA approved the first integrase inhibitor for inclusion in treatment regimens of HIV-1 patients failing their current regimens with multi-drug resistant strains. However, treatment failure has been observed during integrase inhibitor-containing therapy. Several mutational pathways have been described with signature mutations at integrase positions 66, 92, 148 and 155. Therefore, a genotypic assay for the amplification and sequencing of HIV-1 integrase was developed. The assay displayed a detection limit of 10 HIV-1 III(B) RNA copies/ml plasma. As the HIV-1 pandemic is characterised by a large genetic diversity, the new assay was evaluated on a panel of 74 genetically divergent samples belonging to the following genetic forms A, B, C, D, F, G, J, CRF01-AE, CRF02-AG, CRFF03-AB, CRF12-BF and CRF13-cpx. Their viral load ranged from 178 until >500,000 RNA copies/ml. The amplification and sequencing was successful for 70 samples (a success rate of 95%). The four failures were most probably due to low viral load or poor quality of RNA and not to subtype issues. Some of the sequences obtained from integrase inhibitor-naïve patients displayed polymorphisms at integrase positions associated with resistance: 74IV, 138D, 151I, 157Q and 163AE. The relevance of these polymorphisms in the absence of the signature mutations remains unclear.
Published: 2008
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36. Prevalence and epidemiology of HIV type 1 drug resistance among newly diagnosed therapy-naive patients in Belgium from 2003 to 2006.

Author: Vercauteren J, Derdelinckx I, Sasse A, Bogaert M, Ceunen H, De Roo A, De Wit S, Deforche K, 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, van den Heuvel A, van der Gucht B, van Ranst M, van Wijngaerden E, Vandercam B, Vekemans M, Verhofstede C, Clumeck N, Vandamme AM, and van Laethem K
Subjects: Adult, Aged, Aged, 80 and over, Anti-HIV Agents pharmacology, Belgium epidemiology, Female, Genotype, HIV Infections physiopathology, HIV Infections transmission, HIV Protease genetics, HIV Reverse Transcriptase genetics, HIV-1 isolation & purification, Humans, Male, Middle Aged, Molecular Sequence Data, Prospective Studies, RNA, Viral blood, RNA, Viral genetics, RNA, Viral isolation & purification, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Surveys and Questionnaires, Drug Resistance, Viral genetics, HIV Infections epidemiology, HIV Infections virology, HIV-1 drug effects, HIV-1 genetics
Abstract: This study is the first prospective study to assess the prevalence, epidemiology, and risk factors of HIV-1 drug resistance in newly diagnosed HIV-infected patients in Belgium. In January 2003 it was initiated as part of the pan-European SPREAD program, and continued thereafter for four inclusion rounds until December 2006. Epidemiological, clinical, and behavioral data were collected using a standardized questionnaire and genotypic resistance testing was done on a sample taken within 6 months of diagnosis. Two hundred and eighty-five patients were included. The overall prevalence of transmitted HIV-1 drug resistance in Belgium was 9.5% (27/285, 95% CI: 6.6-13.4). Being infected in Belgium, which largely coincided with harboring a subtype B virus, was found to be significantly associated with transmission of drug resistance. The relatively high rate of baseline resistance might jeopardize the success of first line treatment as more than 1 out of 10 (30/285, 10.5%) viruses did not score as fully susceptible to one of the recommended first-line regimens, i.e., zidovudine, lamivudine, and efavirenz. Our results support the implementation of genotypic resistance testing as a standard of care in all treatment-naive patients in Belgium.
Published: 2008
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37. No response to first-line tenofovir+lamivudine+efavirenz despite optimization according to baseline resistance testing: impact of resistant minority variants on efficacy of low genetic barrier drugs.

Author: Van Laethem K, De Munter P, Schrooten Y, Verbesselt R, Van Ranst M, Van Wijngaerden E, and Vandamme AM
Subjects: Adenine therapeutic use, Alkynes, Anti-HIV Agents therapeutic use, Cyclopropanes, HIV-1 growth & development, Humans, Male, Reverse Transcriptase Inhibitors therapeutic use, Tenofovir, Adenine analogs & derivatives, Benzoxazines therapeutic use, Drug Resistance, Multiple, Viral genetics, HIV Infections drug therapy, HIV Infections virology, HIV-1 genetics, Lamivudine therapeutic use, Organophosphonates therapeutic use
Abstract: Background: Resistance testing has been implemented into clinical guidelines as it has shown some beneficial effect on subsequent therapy response., Case Report: Routine population-based genotypic resistance testing for a newly diagnosed HIV-1 patient revealed the presence of resistance mutations M41L, V179D and T215E within reverse transcriptase and no mutations within protease. Four weeks after initiation of the combination tenofovir+lamivudine+efavirenz, no response was observed despite good adherence to therapy and efavirenz drug levels in the therapeutic range. Retrospective single genome sequencing of the baseline sample revealed the presence of minority viral variants with additional mutations: a mutation conferring resistance to lamivudine (M184IV), a thymidine associated mutation (K219R) and mutations possibly associated with non-nucleoside reverse transcriptase resistance (F227S, M230IV)., Conclusions: This case illustrates that undetected drug-resistant minority variants can reduce the efficacy of a normally very potent first-line regimen tenofovir+lamivudine+efavirenz. The presence of drug-resistance mutations at diagnosis should be considered as a warning sign against the use of low genetic barrier drugs in first-line regimens, even when these drugs are considered to be active according to routine resistance testing.
Published: 2007
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38. A genotypic assay for the amplification and sequencing of gag and protease from diverse human immunodeficiency virus type 1 group M subtypes.

Author: Van Laethem K, Schrooten Y, Dedecker S, Van Heeswijck L, Deforche K, Van Wijngaerden E, Van Ranst M, and Vandamme AM
Subjects: DNA Primers, DNA, Complementary, Drug Resistance, Viral genetics, Genes, pol, Genotype, HIV Infections virology, HIV-1 isolation & purification, Humans, Plasma virology, RNA, Viral genetics, Recombination, Genetic, Sensitivity and Specificity, Sequence Analysis, DNA, Genes, gag, HIV Protease genetics, HIV-1 genetics, Reverse Transcriptase Polymerase Chain Reaction methods
Abstract: In human immunodeficiency virus type 1 (HIV-1), an interaction exists between the in vivo evolution of Gag protein and protease to escape from antiretroviral drug selective pressure. Therefore, it was decided to develop a genotypic assay for the amplification and sequencing of HIV-1 gag and protease. As the HIV-1 pandemic is characterised by a large genetic diversity, the assay developed was evaluated on a panel of 28 genetically divergent samples belonging to the following subtypes A1, B, C, D, F1, F2, G, H, J, CRF01-AE, CRF02-AG and CRF13-cpx. The assay displayed a detection limit ranging between 500 RNA copies/ml and 5000 RNA copies/ml plasma. Full-length sequences could be obtained for 25 samples. The population sequences of the three other samples lacked a part of the sequence because of heterogeneous signal, probably due to the presence of quasi-species with insertions/deletions of a different length.
Published: 2006
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39. Molecular testing of multiple HIV-1 transmissions in a criminal case.

Author: Lemey P, Van Dooren S, Van Laethem K, Schrooten Y, Derdelinckx I, Goubau P, Brun-Vézinet F, Vaira D, and Vandamme AM
Subjects: Bayes Theorem, DNA, Viral genetics, Female, Genes, env genetics, Genes, pol genetics, HIV Infections virology, HIV-1 genetics, Humans, Male, Phylogeny, Polymerase Chain Reaction methods, Forensic Medicine methods, HIV Infections transmission, HIV-1 classification, Rape
Abstract: Objective: To test the a priori hypothesis of HIV-1 transmission from one suspect to six recipients in a criminal case., Methods: Partial pol and/or env sequences were obtained for at least two samples of the suspect and the victims. Appropriate local controls were sampled based on epidemiological and subtype criteria. Phylogenetic testing was performed using different reconstruction methods., Results: Phylogenetic analyses consistently inferred a monophyletic cluster for the suspect and victim samples in both genome regions. This was highly supported by parametric and non-parametric bootstrapping techniques. Moreover, the controls most closely related to the suspect-victim cluster had a similar geographical origin to the suspect., Conclusions: Taking into account the limitations on the conclusions that can be drawn from molecular investigations we could infer that our molecular data is consistent with a scenario of multiple HIV transmission between suspect and victims.
Published: 2005
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40. A genotypic resistance assay for the detection of drug resistance in the human immunodeficiency virus type 1 envelope gene.

Author: Van Laethem K, Schrooten Y, Lemey P, Van Wijngaerden E, De Wit S, Van Ranst M, and Vandamme AM
Subjects: HIV Envelope Protein gp120 genetics, HIV Envelope Protein gp41 genetics, HIV-1 classification, HIV-1 genetics, Humans, Microbial Sensitivity Tests, Molecular Sequence Data, Peptide Fragments genetics, Drug Resistance, Viral genetics, Genes, env genetics, HIV-1 drug effects, Sequence Analysis, DNA
Abstract: Since it is not clear yet whether enfuvirtide resistance is restricted to gp41, it was decided to develop a genotypic assay for the detection of drug resistance in the entire human immunodeficiency virus type 1 (HIV-1) env gene. Given the increasing prevalence of HIV-1 non-B subtypes in Europe, it is important to evaluate the performance of the assay on a panel of genetically divergent samples. A panel of 1 laboratory and 10 clinical isolates from 10 patients was tested, all enfuvirtide naive and chosen according to the subtype as determined in the pol region (A, B, C, H, CRF01-AE, CRF02-AG, CRF05-DF, CRF11-cpx and U), while their env sequences belonged to subtypes A, B, C, H, A/G recombinant, B/H recombinant, CRF01-AE, CRF02-AG, CRF05-DF and CRF11-cpx. The detection limits of the gp120 and the gp41 PCRs ranged between 500 and 5000 RNA copies/ml plasma. The highest sensitivity was obtained for the laboratory strain, whereas the detection limit for all patient samples, except for the subtype C sample, was 1000 RNA copies/ml. The numerous insertions and deletions in the gp120 gene, that were often present as quasi-species, necessitated the sequencing of cloned PCR products. The gp41 gene displayed less diversity and less insertions/deletions. Especially, the heptad repeat 1 was highly conserved and none of the enfuvirtide naive samples contained any of the already known enfuvirtide resistance mutations at amino acid positions 36-45. This study demonstrates that the assay is able to genotype genetically diverse HIV-1 strains with a good sensitivity.
Published: 2005
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41. Current levels of drug resistance among therapy-naive HIV-infected patients have significant impact on treatment response.

Author: Derdelinckx I, Van Laethem K, Maes B, Schrooten Y, De Wit S, Florence E, Fransen K, Ribas SG, Marissens D, Moutschen M, Vaira D, Zissis G, Van Ranst M, Van Wijngaerden E, and Vandamme AM
Subjects: Anti-HIV Agents pharmacology, Female, HIV Infections virology, HIV-1 genetics, Humans, Male, Mutation, Reverse Transcriptase Inhibitors pharmacology, Treatment Outcome, Anti-HIV Agents therapeutic use, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV Infections epidemiology, HIV-1 drug effects, Reverse Transcriptase Inhibitors therapeutic use
Published: 2004
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42. Performance of ViroSeq HIV-1 Genotyping System in routine practice at a Belgian clinical laboratory.

Author: Maes B, Schrooten Y, Snoeck J, Derdelinckx I, Van Ranst M, Vandamme AM, and Van Laethem K
Subjects: Belgium, Genetic Techniques, HIV Infections diagnosis, HIV Infections virology, Humans, Nucleic Acid Amplification Techniques, Genotype, HIV-1 classification, HIV-1 genetics, Virology methods
Abstract: Since there are indications of an increasing amount of non-B subtypes in Western Europe it was decided to assess the performance of the ViroSeq HIV-1 Genotyping System on a set of samples from the AIDS Reference Laboratory at the University Hospitals Leuven, a hospital with an increasing number of patients infected with non-B subtypes. The set consisted of 383 samples comprising 12 different subtypes and the genotyping kit was assessed for its amplification capabilities as well as its sequencing capabilities. Amplification failed in 32 samples (8.4%) and there was a tendency of a lower performance of the kit when it concerned the amplification of non-B subtypes. Regarding the sequencing performance of the HIV-1 Genotyping System, three different results could be considered. The performance of the entire set of primers (A, B, C, F, G and H) on the different subtypes showed a significant decrease of positive results for subtypes A, G and the recombinants whereas a tendency to less positive results could be detected for subtypes CRF12_BF, D, H and J. When looking at the performance of the individual primers for the different subtypes, only one result differed significantly: there were less positive results by applying primer F on subtype A. A tendency to less positive results was found for other combinations of primer and subtype, most of which comprised combinations with primers B, C, F and H. A final result was obtained by comparing the overall sequencing results of a certain primer on all the non-B subtypes with the results of the same primer on subtype B. Primer F showed significant less positive results and a tendency to less positive results was found for primer H. The other primers showed comparable results. All of the above results regarding the sequencing primers did not include primer D since this is a back-up primer for primer A. Analysis of the results for primer D showed that less positive results were found for all the non-B subtypes, most of which were significant. The overall performance of primer D on all non-B subtypes was only 15.7%. The use of primer D as a back-up primer was also investigated: it generated a positive result in only 17.3% of the cases where primer A failed. Most of these positive results were subtype B (74%). As a result of sequencing problems 65 out of 351 (18.5%) samples had to be processed with "in-house" procedures.
Published: 2004
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43. Rising prevalence of HIV-1 non-B subtypes in Belgium: 1983-2001.

Author: Snoeck J, Van Laethem K, Hermans P, Van Wijngaerden E, Derdelinckx I, Schrooten Y, van de Vijver DA, De Wit S, Clumeck N, and Vandamme AM
Subjects: Acquired Immunodeficiency Syndrome classification, Adult, Belgium epidemiology, Female, Geography, HIV Infections classification, HIV-1 isolation & purification, Humans, Male, Racial Groups, Sexual Behavior, Acquired Immunodeficiency Syndrome epidemiology, HIV Infections epidemiology, HIV-1 classification
Abstract: This study documented the HIV-1 subtype distribution in 2 Belgian hospitals and determined predictive demographics for non-B subtypes. Overall, subtype B was the most prevalent subtype in this population, followed by subtypes A and C. Several recombinants were detected, circulating recombinants as well as new ones. We found a rise in non-B subtypes from 0% in 1983 to 57% in 2001. The Cochran-Armitage trend test (P < 0.001) as well as the correlation analysis (R = 0.71, P = 0.0006) was highly significant. Recombinants were also increasing in this patient population from 0% in 1983 to 10% in 2001, with good support from the statistical analyses (trend test P < 0.001; correlation analysis R = 0.67, P = 0.0016). Heterosexual route of infection, black African race, African origin of the virus, and year of diagnosis were predictors for infection with non-B subtypes in multivariate analysis. This analysis indicates that the prevalence of non-B subtypes and recombinants in this patient population is high and increasing. Gathering demographic and sequence information from newly diagnosed patients could be useful to further follow the spread of non-B subtypes in Belgium and Europe, but subtyping based on sequence information still remains the most reliable method.
Published: 2004
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44. Performance of the VERSANT HIV-1 resistance assays (LiPA) for detecting drug resistance in therapy-naive patients infected with different HIV-1 subtypes.

Author: Derdelinckx I, Van Laethem K, Maes B, Schrooten Y, De Schouwer K, De Wit S, Fransen K, García Ribas S, Moutschen M, Vaira D, Zissis G, Van Ranst M, Van Wijngaerden E, and Vandamme AM
Subjects: Anti-HIV Agents therapeutic use, Belgium epidemiology, Female, Genotype, HIV Infections drug therapy, HIV Infections virology, HIV Protease genetics, HIV Reverse Transcriptase genetics, HIV-1 genetics, HIV-1 isolation & purification, Humans, Male, Mutation, Nucleic Acid Hybridization, Sequence Analysis, DNA methods, Anti-HIV Agents pharmacology, Drug Resistance, Viral genetics, HIV-1 classification, HIV-1 drug effects, Microbial Sensitivity Tests methods
Abstract: In this study we evaluated the performance of the VERSANT HIV-1 Resistance Assays (LiPA) in detecting drug resistance in therapy-naive HIV-infected patients diagnosed in Belgium in 2000. We compared the results with population sequencing and found concordance to be in line with previous studies in treatment-experienced patients (86.87% for reverse transcriptase (RT); 92.77% for protease (PRO)). Discordance was mainly due to indeterminate reactions on LiPA (8.45% for RT; 6.85% for PRO) and minor discordances (4.13% for RT; 0.25% for PRO). Major discordances were rare (0.46% for RT; 0.12% for PRO). Indeterminate reactions were significantly associated with strains belonging to non-B subtypes.
Published: 2003
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45. A combination of poor adherence and a low baseline susceptibility score is highly predictive for HAART failure.

Author: Van Vaerenbergh K, De Geest S, Derdelinckx I, Bobbaers H, Carbonez A, Deschamps A, De Graeve V, De Saar V, Ceunen H, De Smet K, Maes B, Peetermans W, Schrooten Y, Desmyter J, De Clercq E, Van Ranst M, Van Wijngaerden E, and Vandamme AM
Subjects: Adult, Algorithms, CD4 Lymphocyte Count, Drug Resistance, Viral genetics, Electronics, Genotype, HIV Infections immunology, HIV Infections virology, Humans, Logistic Models, Male, Middle Aged, Patient Compliance, Predictive Value of Tests, RNA, Viral analysis, Treatment Failure, Treatment Refusal, Viral Load, Antiretroviral Therapy, Highly Active, HIV Infections drug therapy, HIV-1 genetics
Abstract: The relationship between adherence, virological response to highly active antiretroviral therapy (HAART) and the presence and development of genotypic resistance was assessed in 41 HIV-infected patients on HAART. Four adherence parameters (drug taking adherence, dosing adherence, timing adherence and drug holidays) were scored prospectively using electronic event monitoring. Genotypic resistance at baseline and after therapy failure was scored retrospectively and a genotype-based susceptibility score was calculated. Overall median adherence rates were high. All adherence parameters were better in virological responders (n=31) compared to non-responders (n=10), drug taking adherence and number of drug holidays being significantly different. Responders had a significantly higher susceptibility score. Stepwise logistic regression showed that the number of drug holidays and a low susceptibility score were highly predictive for therapy failure. Despite the presence of a limited number of baseline resistance mutations, perfectly adherent patients can control virus replication for a prolonged period.
Published: 2002
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