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1. HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012

Author

Pineda-Peña, A.-C. (Andrea-Clemencia), Theys, K. (Kristof), Stylianou, D.C. (Dora C.), Demetriades, I. (I.), Puchhammer, E. (Elisabeth), Vandamme, A.M. (Anne Mieke), Aleksiev, I. (Ivailo), Lepej, S.Z. (Snjezana), Linka, M. (Marek), Fonager, J. (Jannik), Liitsola, K. (Kirsi), Kaiser, R. (Rolf), Hamouda, O. (Osamah), Paraskevis, D. (Dimitrios), Coughlan, S. (Suzie), Grossman, Z. (Zehava), Mor, O. (Orna), Zazzi, M. (Maurizio), Griskevicius, A. (Algirdas), Lipnickiene, V., Devaux, C. (Carole), Boucher, C. (Charles), Hofstra, M. (Marije), Wensing, A. (Amj), Bakken-Kran, A.-M. (Anne-Marte), Horban, A. (Andrzej), Camacho, R.J. (Ricardo Jorge), Paraschiv, C. (Corina), Otelea, D. (Dan), Stanojevic, M. (Maja), Stanekova, D. (Danica), Poljak, M. (Mario), Garcia, F. (Federico), Paredes, R. (Roger), Albert, J. (Jan), Abecasis, A.B. (Ana), Kostrikis, L.G. (Leondios), Pineda-Peña, A.-C. (Andrea-Clemencia), Theys, K. (Kristof), Stylianou, D.C. (Dora C.), Demetriades, I. (I.), Puchhammer, E. (Elisabeth), Vandamme, A.M. (Anne Mieke), Aleksiev, I. (Ivailo), Lepej, S.Z. (Snjezana), Linka, M. (Marek), Fonager, J. (Jannik), Liitsola, K. (Kirsi), Kaiser, R. (Rolf), Hamouda, O. (Osamah), Paraskevis, D. (Dimitrios), Coughlan, S. (Suzie), Grossman, Z. (Zehava), Mor, O. (Orna), Zazzi, M. (Maurizio), Griskevicius, A. (Algirdas), Lipnickiene, V., Devaux, C. (Carole), Boucher, C. (Charles), Hofstra, M. (Marije), Wensing, A. (Amj), Bakken-Kran, A.-M. (Anne-Marte), Horban, A. (Andrzej), Camacho, R.J. (Ricardo Jorge), Paraschiv, C. (Corina), Otelea, D. (Dan), Stanojevic, M. (Maja), Stanekova, D. (Danica), Poljak, M. (Mario), Garcia, F. (Federico), Paredes, R. (Roger), Albert, J. (Jan), Abecasis, A.B. (Ana), and Kostrikis, L.G. (Leondios)

Abstract

Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings.

Published
2018
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2. The global spread of HIV-1 subtype B epidemic

Author

Magiorkinis, G. (Gkikas), Angelis, K. (Konstantinos), Mamais, I. (Ioannis), Katzourakis, A. (Aris), Hatzakis, A. (Angelos), Albert, J. (Jan), Lawyer, G. (Glenn), Hamouda, O. (Osamah), Struck, D. (Daniel), Vercauteren, J. (Jurgen), Wensing, A. (Amj), Alexiev, I. (Ivailo), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Gomes, P. (Perpétua), Camacho, R.J. (Ricardo Jorge), Coughlan, S. (Suzie), Griskevicius, A. (Algirdas), Grossman, Z. (Zehava), Horban, A. (Anders), Kostrikis, L.G. (Leondios), Lepej, S.J. (Snjezana J.), Liitsola, K. (Kirsi), Linka, M. (Marek), Nielsen, C., Otelea, D. (Dan), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Schmit, J.C., Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Stylianou, D.C. (Dora C.), Boucher, C.A.B. (Charles), Nikolopoulos, G. (Georgios), Vasylyeva, T. (Tetyana), Friedman, S.R. (Samuel R.), Vijver, D.A.M.C. (David) van de, Angarano, G. (Guiseppe), Chaix, M.L. (Marie Laure), Luca, A. (Andrea) de, Korn, K. (Klaus), Loveday, C. (Clive), Soriano, V. (Virtudes), Yerly, S. (Sabine), Zazzi, M., Vandamme, A.M. (Anne Mieke), Paraskevis, D. (Dimitrios), Magiorkinis, G. (Gkikas), Angelis, K. (Konstantinos), Mamais, I. (Ioannis), Katzourakis, A. (Aris), Hatzakis, A. (Angelos), Albert, J. (Jan), Lawyer, G. (Glenn), Hamouda, O. (Osamah), Struck, D. (Daniel), Vercauteren, J. (Jurgen), Wensing, A. (Amj), Alexiev, I. (Ivailo), Åsjö, B. (Birgitta), Balotta, C. (Claudia), Gomes, P. (Perpétua), Camacho, R.J. (Ricardo Jorge), Coughlan, S. (Suzie), Griskevicius, A. (Algirdas), Grossman, Z. (Zehava), Horban, A. (Anders), Kostrikis, L.G. (Leondios), Lepej, S.J. (Snjezana J.), Liitsola, K. (Kirsi), Linka, M. (Marek), Nielsen, C., Otelea, D. (Dan), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Schmit, J.C., Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Stylianou, D.C. (Dora C.), Boucher, C.A.B. (Charles), Nikolopoulos, G. (Georgios), Vasylyeva, T. (Tetyana), Friedman, S.R. (Samuel R.), Vijver, D.A.M.C. (David) van de, Angarano, G. (Guiseppe), Chaix, M.L. (Marie Laure), Luca, A. (Andrea) de, Korn, K. (Klaus), Loveday, C. (Clive), Soriano, V. (Virtudes), Yerly, S. (Sabine), Zazzi, M., Vandamme, A.M. (Anne Mieke), and Paraskevis, D. (Dimitrios)

Abstract

Human immunodeficiency virus type 1 (HIV-1) was discovered in the early 1980s when the virus had already established a pandemic. For at least three decades the epidemic in the Western World has been dominated by subtype B infections, as part of a sub-epidemic that traveled from Africa through Haiti to United States. However, the pattern of the subsequent spread still remains poorly understood. Here we analyze a large dataset of globally representative HIV-1 subtype B strains to map their spread around the world over the last 50. years and describe significant spread patterns. We show that subtype B travelled from North America to Western Europe in different occasions, while Central/Eastern Europe remained isolated for the most part of the early epidemic. Looking with more detail in European countries we see that the United Kingdom, France and Switzerland exchanged viral isolates with non-European countries than with European ones. The observed pattern is likely to mirror geopolitical landmarks in the post-World War II era, namely the rise and the fall of the Iron Curtain and the European colonialism. In conclusion, HIV-1 spread through specific migration routes which are consistent with geopolitical factors that affected human activities during the last 50. years, such as migration, tourism and trade. Our findings support the argument that epidemic control policies should be global and incorporate political and socioeconomic factors. . . .

Published
2016
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3. Patterns of transmitted HIV drug resistance in Europe vary by risk group

Author

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

Abstract

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

Published
2014
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4. HIV-1 fitness landscape models for indinavir treatment pressure using observed evolution in longitudinal sequence data are predictive for treatment failure

Author

Sangeda, R.Z. (Raphael), Theys, K. (Kristof), Beheydt, G. (Gertjan), Rhee, S.Y. (Soo Yoon), Deforche, K. (Koen), Vercauteren, J. (Jurgen), Libin, P. (Pieter), Imbrechts, S. (Stijn), Grossman, Z. (Zehava), Camacho, R.J. (Ricardo Jorge), Laethem, K. (Kristel) van, Pironti, A. (Alejandro), Zazzi, M. (Maurizio), Sönnerborg, A. (Anders), Incardona, F. (Francesca), Luca, A. (Andrea) de, Torti, C. (Carlo), Ruiz, L. (Lidia), Vijver, D.A.M.C. (David) van de, Shafer, R.W. (Robert), Bruzzone, B. (Bianca), Wijngaerden, E. (Eric) van, Vandamme, A.M. (Anne Mieke), Sangeda, R.Z. (Raphael), Theys, K. (Kristof), Beheydt, G. (Gertjan), Rhee, S.Y. (Soo Yoon), Deforche, K. (Koen), Vercauteren, J. (Jurgen), Libin, P. (Pieter), Imbrechts, S. (Stijn), Grossman, Z. (Zehava), Camacho, R.J. (Ricardo Jorge), Laethem, K. (Kristel) van, Pironti, A. (Alejandro), Zazzi, M. (Maurizio), Sönnerborg, A. (Anders), Incardona, F. (Francesca), Luca, A. (Andrea) de, Torti, C. (Carlo), Ruiz, L. (Lidia), Vijver, D.A.M.C. (David) van de, Shafer, R.W. (Robert), Bruzzone, B. (Bianca), Wijngaerden, E. (Eric) van, and Vandamme, A.M. (Anne Mieke)

Abstract

We previously modeled the in vivo evolution of human immunodeficiency virus-1 (HIV-1) under drug selective pressure from cross-sectional viral sequences. These fitness landscapes (FLs) were made by using first a Bayesian network (BN) to map epistatic substitutions, followed by scaling the fitness landscape based on an HIV evolution simulator trying to evolve the sequences from treatment naïve patients into sequences from patients failing treatment. In this study, we compared four FLs trained with different sequence populations. Epistatic interactions were learned from three different cross-sectional BNs, trained with sequence from patients experienced with indinavir (BNT), all protease inhibitors (PIs) (BNP) or all PI except indinavir (BND). Scaling the fitness landscape was done using cross-sectional data from drug naïve and indinavir experienced patients (Fcross using BNT) and using longitudinal sequences from patients failing indinavir (FlongT using BNT, FlongP using BNP, FlongD using BND). Evaluation to predict the failing sequence and therapy outcome was performed on independent sequences of patients on indinavir. Parameters included estimated fitness (LogF), the number of generations (GF) or mutations (MF) to reach the fitness threshold (average fitness when a major resistance mutation appeared), the number of generations (GR) or mutations (MR) to reach a major resistance mutation and compared to genotypic susceptibility score (GSS) from Rega and HIVdb algorithms. In pairwise FL comparisons we found significant correlation between fitness values for individual sequences, and this correlation improved after correcting for the subtype. Furthermore, FLs could predict the failing sequence under indinavir-containing combinations. At 12 and 48 weeks, all parameters from all FLs and indinavir GSS (both for Rega and HIVdb) were predictive of therapy outcome, except MR for FlongT and FlongP. The fitness landscapes have similar predictive power for treatment response un

Published
2013
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5. RegaDB: Community-driven data management and analysis for infectious diseases

Author

Libin, P. (Pieter), Beheydt, G. (Gertjan), Deforche, K. (Koen), Imbrechts, S. (Stijn), Ferreira, F. (Fossie), Laethem, K. (Kristel) van, Theys, K. (Kristof), Carvalho, A.P. (Ana Patricia), Cavaco-Silva, J. (Joana), Lapadula, G. (Giuseppe), Torti, C. (Carlo), Assel, M. (Matthias), Wesner, S. (Stefan), Snoeck, M.M.J. (M. M J), Ruelle, J. (Jean), Bel, A.V. (Annelies) de, Lacor, P. (Patrick), Munter, P. (Paul) de, Wijngaerden, E. (Eric) van, Zazzi, M. (Maurizio), Kaiser, R. (Rolf), Ayouba, A. (Ahidjo), Peeters, M.C. (Marian), Oliveira, T. (Tulio) de, Alcantara, L.C.J. (Luiz), Grossman, Z. (Zehava), Sloot, P.M.A. (Peter), Otelea, D. (Dan), Paraschiv, C. (Corina), Boucher, C.A.B. (Charles), Camacho, R.J. (Ricardo Jorge), Vandamme, A.M. (Anne Mieke), Libin, P. (Pieter), Beheydt, G. (Gertjan), Deforche, K. (Koen), Imbrechts, S. (Stijn), Ferreira, F. (Fossie), Laethem, K. (Kristel) van, Theys, K. (Kristof), Carvalho, A.P. (Ana Patricia), Cavaco-Silva, J. (Joana), Lapadula, G. (Giuseppe), Torti, C. (Carlo), Assel, M. (Matthias), Wesner, S. (Stefan), Snoeck, M.M.J. (M. M J), Ruelle, J. (Jean), Bel, A.V. (Annelies) de, Lacor, P. (Patrick), Munter, P. (Paul) de, Wijngaerden, E. (Eric) van, Zazzi, M. (Maurizio), Kaiser, R. (Rolf), Ayouba, A. (Ahidjo), Peeters, M.C. (Marian), Oliveira, T. (Tulio) de, Alcantara, L.C.J. (Luiz), Grossman, Z. (Zehava), Sloot, P.M.A. (Peter), Otelea, D. (Dan), Paraschiv, C. (Corina), Boucher, C.A.B. (Charles), Camacho, R.J. (Ricardo Jorge), and Vandamme, A.M. (Anne Mieke)

Abstract

Summary: RegaDB is a free and open source data management and analysis environment for infectious diseases. RegaDB allows clinicians to store, manage and analyse patient data, including viral genetic sequences. Moreover, RegaDB pro

Published
2013
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6. Limited cross-border infections in patients newly diagnosed with HIV in Europe

Author

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

Abstract

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

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

Author

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

Abstract

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

Published
2013
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8. Treatment-associated polymorphisms in protease are significantly associated with higher viral load and lower CD4 count in newly diagnosed drug-naive HIV-1 infected patients

Author

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

Abstract

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

Published
2012
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9. Cellular HIV-1 DNA levels in drug sensitive strains are equivalent to those in drug resistant strains in newly-diagnosed patients in Europe

Author

Demetriou, V.L. (Victoria), Vijver, D.A.M.C. (David) van de, Kousiappa, I. (Ioanna), Balotta, C. (Claudia), Clotet, B. (Bonaventura), Grossman, Z. (Zehava), Jørgensen, L.B. (Louise), Lepej, S.Z. (Snjezana), Levy, I. (Itzchak), Nielsen, C. (Claus), Paraskevis, D. (Dimitrios), Poljak, M. (Mario), Roman, F. (Francois), Ruiz, L. (Lidia), Schmidt, J.C., Vandamme, A.M. (Anne Mieke), Laethem, K. (Kristel), Vercauteren, J. (Jurgen), Kostrikis, L.G. (Leondios), Demetriou, V.L. (Victoria), Vijver, D.A.M.C. (David) van de, Kousiappa, I. (Ioanna), Balotta, C. (Claudia), Clotet, B. (Bonaventura), Grossman, Z. (Zehava), Jørgensen, L.B. (Louise), Lepej, S.Z. (Snjezana), Levy, I. (Itzchak), Nielsen, C. (Claus), Paraskevis, D. (Dimitrios), Poljak, M. (Mario), Roman, F. (Francois), Ruiz, L. (Lidia), Schmidt, J.C., Vandamme, A.M. (Anne Mieke), Laethem, K. (Kristel), Vercauteren, J. (Jurgen), and Kostrikis, L.G. (Leondios)

Abstract

Background HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load. Methodology/Principal Findings Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log10HIV-1copies/106PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4+T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two. Conclusions/Significance An improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furthe

Published
2010
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10. Tracing the HIV-1 subtype B mobility in Europe: A phylogeographic approach

Author

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

Abstract

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

Published
2009
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