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