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1. Effectiveness of integrase strand transfer inhibitor-based regimens in HIV-infected treatment-naive individuals: results from a European multi-cohort study

Author

Rossetti, B., Fabbiani, M., Di Carlo, D., Incardona, F., Abecasis, A., Gomes, P., Geretti, A. M., Seguin-Devaux, C., Garcia, F., Kaiser, R., Modica, S., Shallvari, A., Sonnerborg, A., Zazzi, M., Bobkova, M., Paredes, R., Sayan, M., and Vandamme, A. M.

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Pyridones, 030106 microbiology, Drug Resistance, Integrase inhibitor, HIV Infections, Drug resistance, 3-Ring, Cohort Studies, Drug Resistance, Viral, Heterocyclic Compounds, 3-Ring, Humans, Integrases, Oxazines, Raltegravir Potassium, HIV Integrase Inhibitors, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Heterocyclic Compounds, Internal medicine, medicine, Pharmacology (medical), Viral, 030212 general & internal medicine, Pharmacology, Elvitegravir, business.industry, Raltegravir, Discontinuation, Infectious Diseases, chemistry, Dolutegravir, business, Viral load, medicine.drug, Cohort study
Abstract

Background INSTIs have become a pillar of first-line ART. Real-world data are needed to assess their effectiveness in routine care. Objectives We analysed ART-naive patients who started INSTI-based regimens in 2012–19 whose data were collected by INTEGRATE, a European collaborative study including seven national cohorts. Methods Kaplan–Meier analyses assessed time to virological failure (VF), defined as one viral load (VL) ≥1000 copies/mL, two consecutive VLs ≥50 copies/mL, or one VL ≥50 copies/mL followed by treatment change after ≥24 weeks of follow-up, and time to INSTIs discontinuation (INSTI-DC) for any reason. Factors associated with VF and INSTI-DC were explored by logistic regression analysis. Results Of 2976 regimens started, 1901 (63.9%) contained dolutegravir, 631 (21.2%) elvitegravir and 444 (14.9%) raltegravir. The 1 year estimated probabilities of VF and INSTI-DC were 5.6% (95% CI 4.5–6.7) and 16.2% (95% CI 14.9–17.6), respectively, and were higher for raltegravir versus both elvitegravir and dolutegravir. A baseline VL ≥100 000 copies/mL [adjusted HR (aHR) 2.17, 95% CI 1.55–3.04, P 3 drugs versus 3 drugs (aHR 2.73, 95% CI 1.55–4.79, P Conclusions This large multi-cohort study indicates high effectiveness of elvitegravir- or dolutegravir-based first-line ART in routine practice across Europe.

Published
2021
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2. Outpatient management or hospitalization of patients with proven or suspected SARS-CoV-2 infection: The HOME-CoV rule

Author

Douillet D., Mahieu R., Boiveau V., Vandamme Y.-M., Armand A., Morin F., Savary D., Dubée V., Annweiler C., and Roy P.-M.

Subjects
3. Good health
Abstract

In the context of the COVID-19 pandemic and overloaded hospitals, a central issue is the need to define reliable and consensual criteria for hospitalization or outpatient management in mild cases of COVID-19. Our aim was to define an easy-to-use clinical rule aiming to help emergency physicians in hospitalization or outpatient management decision-making for patients with suspected or confirmed SARS-CoV-2 infection (the HOME-CoV Rule). The Delphi method was used to reach a consensus of a large panel of 51 experts: emergency physicians, geriatricians, infectious disease specialists, and ethical consultants. A preliminary list of eligible criteria was compiled based on a literature review. Four rounds of anonymized expert consultations were performed. The experts were asked to score each item as relevant, possibly relevant and non-relevant, as major or minor, and to choose the cut-off. They were also able make suggestions and remarks. Eight criteria constituting the HOME-CoV were selected: six correspond to the severity of clinical signs, one to the clinical course (clinically significant worsening within the last 24 hours), and the last corresponds to the association of a severe comorbidity and an inadequate living context. Hospitalization is deemed necessary if a patient meets one or more of the criteria. In the end, 94.4% of the experts agreed with the defined rule. Thanks to the Delphi method, an absolute consensus was obtained of a large panel of experts on the HOME-CoV rule, a decision-making support mechanism for clinicians to target patients with suspected or confirmed COVID-19 requiring hospitalization.Trial registration: NCT04338841

Published
2020
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5. A21 HIV-1 sub-subtype F1 outbreak among MSM in Belgium

Author

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

Published
2017

6. 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

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

Author

Frentz, D., Van De Vijver, D., Abecasis, A. B., Albert, Jan, Hamouda, O., Jørgensen, L., Kücherer, C., Struck, D., Schmit, J. -C, Vercauteren, J., Åsjö, Birgitta, Balotta, Claudia, Bergin, C., Beshkov, Danail, Camacho, Ricardo J., Clotet, B., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, Leontios G., Linka, K. L. M., Nielsen, C., Otelea, D., Paraskevis, Dimitrios N., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Sönnerborg, A., Stanekova, D., Stanojevic, M., Vandamme, A. -M, Boucher, C., Wensing, A., Kostrikis, Leontios G. [0000-0002-5340-7109], Paraskevis, Dimitrios [0000-0001-6167-7152], Frentz, D., van de Vijver, D., Abecasis, A., Albert, J., Hamouda, O., Jørgensen, L., Kücherer, C., Struck, D., Schmit, J., Vercauteren, J., Asjö, B., Balotta, C., Bergin, C., Beshkov, D., Camacho, R., Clotet, B., Griskevicius, A., Grossman, Z., Horban, A., Kolupajeva, T., Korn, K., Kostrikis, L., Linka, K., Nielsen, C., Otelea, D., Paraskevis, D., Paredes, R., Poljak, M., Puchhammer-Stöckl, E., Sönnerborg, A., Stanekova, D., Stanojevic, M., Vandamme, A., Wensing, A., and Tramuto, F. among SPREAD Programme investigators, Graduate School, Sluis-Cremer, Nicolas, Van Wijngaerden, Eric, Virology, and Erasmus MC other

Subjects
Male, Epidemiology, genotype, Human immunodeficiency virus 1, HIV Infections, RNA directed DNA polymerase inhibitor, high risk patient, Logistic regression, Settore MED/42 - Igiene Generale E Applicata, Men who have sex with men, 0302 clinical medicine, Immunodeficiency Viruses, middle aged, statistics and numerical data, 10. No inequality, Substance Abuse, Intravenous, 0303 health sciences, adult, transmission, virus diseases, virus transmission, highly active antiretroviral therapy, HIV immunopathogenesis, 3. Good health, Medical Microbiology, Viral Pathogens, high risk behavior, Medicine, Science & Technology - Other Topics, POPULATIONS, health program, anti human immunodeficiency virus agent, USERS, medicine.medical_specialty, Science, Sexual Behavior, Immunology, Sexually Transmitted Diseases, intravenous drug abuse, Microbiology, 03 medical and health sciences, Antibiotic resistance, SDG 3 - Good Health and Well-being, Human immunodeficiency virus infection, proteinase inhibitor, Humans, Protease Inhibitors, human, Heterosexuality, Microbial Pathogens, seroconversion, Medicine and health sciences, Science & Technology, Genitourinary Infections, MUTATIONS, Virology, major clinical study, Logistic Models, transmitted drug resistance mutation, HIV-1, Viral Diseases, Medical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical immunology: 716 [VDP], drug response, men who have sex with men, Drug resistance, Clinical immunology, geography, APPEARANCE, male homosexuality, Medizinische Fakultät, immune system diseases, INFECTION, Medicine and Health Sciences, substance abuse, 030212 general & internal medicine, risk, Multidisciplinary, ACTIVE ANTIRETROVIRAL THERAPY, Transmission (medicine), virus mutation, article, Obstetrics and Gynecology, HIV diagnosis and management, Middle Aged, virology, Multidisciplinary Sciences, Europe, Infectious Diseases, female, Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716 [VDP], Reverse Transcriptase Inhibitors, HIV clinical manifestations, Female, epidemiology, blood sampling, HIV drug resistance, Research Article, Adult, Risk, risk-group, Anti-HIV Agents, Urology, prevalence, Infectious Disease Epidemiology, sexual behavior, Risk-Taking, male, antiviral resistance, Internal medicine, Drug Resistance, Viral, medicine, controlled study, ddc:610, Homosexuality, Male, 030304 developmental biology, drug resistance, Biology and life sciences, business.industry, statistical model, HIV, CD4 lymphocyte count, heterosexuality, nonnucleoside reverse transcriptase inhibitor, Human immunodeficiency virus 1 infection, Diagnostic medicine, INDIVIDUALS, drug effects, Women's Health, business, trend study
Abstract

BACKGROUND: In Europe, a continuous programme (SPREAD) has been in place for ten years to study transmission of drug resistant HIV. We analysed time trends of transmitted drug resistance mutations (TDRM) in relation to the risk behaviour reported. METHODS: HIV-1 patients newly diagnosed in 27 countries from 2002 through 2007 were included. Inclusion was representative for risk group and geographical distribution in the participating countries in Europe. Trends over time were calculated by logistic regression. RESULTS: From the 4317 patients included, the majority was men-having-sex-with-men -MSM (2084, 48%), followed by heterosexuals (1501, 35%) and injection drug users (IDU) (355, 8%). MSM were more often from Western Europe origin, infected with subtype B virus, and recently infected (

Published
2014

8. 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

9. The demise of multidrug-resistant HIV-1: the national time trend in Portugal

Author

Vercauteren, J., Theys, K., Carvalho, A. P., Valadas, E., Duque, L. M., Teofilo, E., Faria, T., Faria, D., Vera, J., Aguas, M. J., Peres, S., Mansinho, K., Vandamme, A.-M., Camacho, R. J., Claudia Miranda, A., Aldir, I., Ventura, F., Nina, J., Borges, F., Doroana, M., Antunes, F., Joao Aleixo, M., Joao Aguas, M., Botas, J., Branco, T., Vaz Pinto, I., Pocas, J., Sa, J., Duque, L., Diniz, A., Mineiro, A., Gomes, F., Santos, C., Fonseca, P., Proenca, P., Tavares, L., Guerreiro, C., Narciso, J., Pinheiro, S., Germano, I., Caixas, U., Faria, N., Paula Reis, A., Bentes Jesus, M., Amaro, G., Roxo, F., Abreu, R., and Neves, I.

Subjects
Microbiology (medical), Drug, medicine.medical_specialty, Anti-HIV Agents, media_common.quotation_subject, antiretroviral therapy, Human immunodeficiency virus (HIV), Mutation, Missense, HIV Infections, Drug resistance, medicine.disease_cause, drug susceptibility, resistance, 03 medical and health sciences, Viral Proteins, Acquired immunodeficiency syndrome (AIDS), Internal medicine, Drug Resistance, Viral, medicine, Prevalence, Humans, Pharmacology (medical), 030304 developmental biology, media_common, Original Research, Pharmacology, 0303 health sciences, CHLC MED, Portugal, 030306 microbiology, business.industry, Drug susceptibility, medicine.disease, therapy failure, Antiretroviral therapy, Virology, 3. Good health, Multiple drug resistance, AIDS, Infectious Diseases, Cohort, HIV-1, business
Abstract

Received 17 July 2012; returned 8 September 2012; revised 2 October 2012; accepted 30 October 2012Objectives: Despite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviraltreatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistantviruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR)over time in a cohort of HIV-1-infected patients in Portugal.Patients and methods: We used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fullyactive drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese NationalAuthority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR.Results: We observed a statistically significant decrease in the prevalence of MDR over the last decade, from6.9% (95% CI: 5.7–8.4) in 2001–03, 6.0% (95% CI: 4.9–7.2) in 2003–05, 3.7% (95% CI: 2.8–4.8) in 2005–07and 1.6% (95% CI: 1.1–2.2) in 2007–09 down to 0.6% (95% CI: 0.3–0.9) in 2009–12 [OR¼0.80 (95% CI:0.75–0.86); P,0.001]. In July 2011 the last new case of MDR was seen.Conclusions: The prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the in-creasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety andpractical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacyagainst resistant strains.Keywords: resistance, drug susceptibility, therapy failure, antiretroviral therapy, AIDS

Published
2012

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

Author

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

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

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

Published
2009

11. Re-analysis of human immunodeficiency virus type 1 isolates from Cyprus and Greece, initially designated 'subtype I', reveals a unique complex A/G/H/K/? mosaic pattern

Author

Paraskevis, Dimitrios N., Magiorkinis, M., Vandamme, A. M., Kostrikis, Leontios G., Hatzakis, Angelos E., Kostrikis, Leontios G. [0000-0002-5340-7109], and Paraskevis, Dimitrios [0000-0001-6167-7152]

Subjects
virus strain, RNA viruses, virus virulence, genetic epidemiology, Gene Products, vif, sequence analysis, HIV Antigens, gene order, HIV Core Protein p24, Human immunodeficiency virus 1, Gene Products, gag, Gene Products, pol, gene sequence, genetic analysis, HIV Envelope Protein gp120, epidemic, Viral Proteins, Capsid, Human immunodeficiency virus infection, Humans, controlled study, viral genetics, human, virus classification, strain difference, Phylogeny, Recombination, Genetic, virus isolation, nonhuman, Greece, Human immunodeficiency virus, article, virus recombination, virus diseases, HIV Envelope Protein gp41, mosaicism, priority journal, Cyprus, HIV-1, virus recombinant, Capsid Proteins, population research
Abstract

Human immunodeficiency virus type 1 (HIV-1) has been classified into three main groups and 11 distinct subtypes. Moreover, several circulating recombinant forms (CRFs) of HIV-1 have been recently documented to have spread widely causing extensive HIV-1 epidemics. A subtype, initially designated I (CRFO4∐x), was documented in Cyprus and Greece and was found to comprise regions of sequence derived from subtypes A and G as well as regions of unclassified sequence. Reanalysis of the three full-length CRFO4∐x sequences that were available revealed a mosaic genomic organization of unique complexity comprising regions of sequence from at least five distinct subtypes, A, G, H, K and unclassified regions. These strains account for approximately 2% of the total HIV-1-infected population in Greece, thus providing evidence of the great capability of HIV-1 to recombine and produce highly divergent strains which can be spread successfully through different infection routes. 82 575 580 Cited By :18

Published
2001

16. Second Spanish Consensus on the Use of Drug Resistance Testing in Clinical Practice (Madrid, March 2000)

Author

Soriano, V., Ledesma, E., Aguilera, A., Antela, A., Arribas, J., Barreiro, P., Blanco, F., Briones, C., Clotet, B., Dalmau, D., Gatell, J. M., Gonzales-Lahoz, J., Leal, M., Martinez-Picado, X., Mendoza, C., Miro, J. M., Moreno, S., Pedreina, J., Podzamczer, D., Pumarola, T., Rodriguez, C., Rodriguez-Rosado, R., Del Romero, J., Rafael Rubio García, Ruiz, L., Havlir, D., Vandamme, A. -M, Wainberg, M., and Youle, M.

20. European recommendations for the clinical use of HIV drug resistance testing: 2011 update

Author

Vandamme, A. -M, Camacho, R. J., Ceccherini-Silberstein, F., Luca, A., Palmisano, L., Paraskevis, D., Paredes, R., Poljak, M., Schmit, J. -C, Soriano, V., Walter, H., Sönnerborg, A., Ait-Khaled, M., Albert, J., Åsjö, B., Bacheler, L., Banhegyi, D., Boucher, C., Brun-Vézinet, F., Clotet, B., Béthune, M. -P, Wit, S., Dressler, S., Elston, R., Gatell, J., Geretti, A. M., Gerstoft, J., Günthard, H. F., Hall, W. W., Hazuda, D., Horban, A., Đorđe Jevtović, Kaiser, R., Lataillade, M., Lundgren, J. D., Marlowe, N., Maroldo, L., Miller, M., Nielsen, C., Perno, C. F., Petropoulos, C., Phillips, A., Schapiro, J., Schuurman, R., Simen, B. B., Stephan, C., Stürmer, M., Suni, J., Teofilo, E., Tsertsvadze, T., Westby, M., Yerly, S., and Youle, M.

21. Multi-science decision support for HIV drug resistance treatment

Author

Peter Sloot, Coveney, P., Bubak, M. T., Vandamme, A. -M, Nualláin, B. O., Vijver, D., Boucher, C., and Computational Science Lab (IVI, FNWI)

Abstract

The complete cascade from genome, proteome, metabolome, and physiome, to health forms multiscale, multiscience systems and crosses many orders of magnitude in temporal and spatial scales. The interactions between these systems create exquisite multitiered networks, with each component in nonlinear contact with many interaction partners. Understanding, quantifying, and handling this complexity is one of the biggest scientific challenges of our time. In this paper we argue that computer science in general, and Grid computing in particular, provide the language needed to study and understand these systems, and discuss a case study in decision support for HIV drug resistance treatment within the European ViroLab project.

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