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

Author

Hofstra, L.M. (Marije), Sauvageot, N. (Nicolas), Albert, J. (Jan), Alexiev, I. (Ivailo), Garcia, F. (Federico), Struck, D. (Daniel), Vijver, D.A.M.C. (David) van de, Åsjö, B. (Birgitta), Beshkov, D. (Danail), Coughlan, S. (Suzie), Descamps, D. (Diane), Griskevicius, A. (Algirdas), Hamouda, O. (Osamah), Horban, A. (Andrzej), Kasteren, M.E.E. (Marjo) van, Kolupajeva, T. (Tatjana), Kostrikis, L.G. (Leondios), Liitsola, K. (Kirsi), Linka, M. (Marek), Mor, O. (Orna), Nielsen, C. (Claus), Otelea, D. (Dan), Paraskevis, D. (Dimitrios), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stockl, E. (Elisabeth), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Van Laethem, K. (Kristel), Zazzi, M. (Maurizio), Zidovec Lepej, S. (Snjezana), Boucher, C.A.B. (Charles), Schmit, J.-C. (Jean-Claude), Wensing, A.M.J. (Annemarie), Hofstra, L.M. (Marije), Sauvageot, N. (Nicolas), Albert, J. (Jan), Alexiev, I. (Ivailo), Garcia, F. (Federico), Struck, D. (Daniel), Vijver, D.A.M.C. (David) van de, Åsjö, B. (Birgitta), Beshkov, D. (Danail), Coughlan, S. (Suzie), Descamps, D. (Diane), Griskevicius, A. (Algirdas), Hamouda, O. (Osamah), Horban, A. (Andrzej), Kasteren, M.E.E. (Marjo) van, Kolupajeva, T. (Tatjana), Kostrikis, L.G. (Leondios), Liitsola, K. (Kirsi), Linka, M. (Marek), Mor, O. (Orna), Nielsen, C. (Claus), Otelea, D. (Dan), Paraskevis, D. (Dimitrios), Paredes, R. (Roger), Poljak, M. (Mario), Puchhammer-Stockl, E. (Elisabeth), Sonnerborg, A. (Anders), Stanekova, D. (Danica), Stanojevic, M. (Maja), Van Laethem, K. (Kristel), Zazzi, M. (Maurizio), Zidovec Lepej, S. (Snjezana), Boucher, C.A.B. (Charles), Schmit, J.-C. (Jean-Claude), and Wensing, A.M.J. (Annemarie)

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.

Published
2016
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4. Primary resistance to integrase strand-transfer inhibitors in Europe.

Author

Casadellá, M., van Ham, P.M. (Petra), Noguera-Julian, M., van Kessel, A., Pou, C., Hofstra, L.M. (Marije), Metcalf, G.A. (Ginger A.), Garcia, F., Struck, D. (Daniel), Alexiev, I. (Ivailo), Bakken Kran, A.M., Hoepelman, A.I.M., Kostrikis, L.G. (Leondios), Somogyi, S., Liitsola, K. (Kirsi), Linka, M. (Marek), Nielsen, C., Otelea, D. (Dan), Paraskevis, D. (Dimitrios), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Stanekova, D. (Danica), Stanojevic, M. (Maja), Van Laethem, K. (Kristel), Zidovec Lepej, S. (Snjezana), Clotet, B., Boucher, C.A.B. (Charles), Paredes, R. (Roger), Wensing, A.M.J. (Annemarie), Casadellá, M., van Ham, P.M. (Petra), Noguera-Julian, M., van Kessel, A., Pou, C., Hofstra, L.M. (Marije), Metcalf, G.A. (Ginger A.), Garcia, F., Struck, D. (Daniel), Alexiev, I. (Ivailo), Bakken Kran, A.M., Hoepelman, A.I.M., Kostrikis, L.G. (Leondios), Somogyi, S., Liitsola, K. (Kirsi), Linka, M. (Marek), Nielsen, C., Otelea, D. (Dan), Paraskevis, D. (Dimitrios), Poljak, M. (Mario), Puchhammer-Stöckl, E. (Elisabeth), Stanekova, D. (Danica), Stanojevic, M. (Maja), Van Laethem, K. (Kristel), Zidovec Lepej, S. (Snjezana), Clotet, B., Boucher, C.A.B. (Charles), Paredes, R. (Roger), and Wensing, A.M.J. (Annemarie)

Abstract

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. 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 InSTI-resistant HIV, 65 samples were selected for 454 integrase sequencing. For the population sequencing analysis, 278 samples were retrieved and successfully analysed. No signature resistance mutations to any of the InSTIs were detected. Eleven (4%) subjects had mutations at resistance-associated positions with an HIVdb score ≥ 10. Of the 56 samples successfully analysed with 454 sequencing, no InSTI signature mutations were detected, whereas integrase substitutions with an HIVdb score ≥ 10 were found in 8 (14.3%) individuals. No signature InSTI-resistant variants were circulating in Europe before the introduction of

Published
2015
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5. Trends and predictors of transmitted drug resistance (TDR) and clusters with TDR in a local Belgian HIV-1 epidemic

Author

Pineda-Peña, A.-C. (Andrea-Clemencia), Schrooten, J., Vinken, L. (Lore), Ferreira, F. (Fossie), Li, G. (Guangdi), Trovão, N.S. (Nídia Sequeira), Khouri, R. (Ricardo), Derdelinck, I. (Inge), Munter, P. (Paul) de, K̈ucherer, C. (C.), Kostrikis, L.G. (Leondios), Nielsen, C. (Claus), Littsola, K. (Kirsi), Wensing, A.M.J. (Annemarie), Stanojevic, M. (Maja), Paredes, R. (Roger), Balotta, C. (Claudia), Albert, J. (Jan), Boucher, C.A.B. (Charles), Gomez-Lopez, A. (Arley), Wijngaerden, E. (Eric) van, Ranst, M. (Marc) van, Vercauteren, J. (Jurgen), Vandamme, A.M. (Anne Mieke), Laethem, K. (Kristel) van, Pineda-Peña, A.-C. (Andrea-Clemencia), Schrooten, J., Vinken, L. (Lore), Ferreira, F. (Fossie), Li, G. (Guangdi), Trovão, N.S. (Nídia Sequeira), Khouri, R. (Ricardo), Derdelinck, I. (Inge), Munter, P. (Paul) de, K̈ucherer, C. (C.), Kostrikis, L.G. (Leondios), Nielsen, C. (Claus), Littsola, K. (Kirsi), Wensing, A.M.J. (Annemarie), Stanojevic, M. (Maja), Paredes, R. (Roger), Balotta, C. (Claudia), Albert, J. (Jan), Boucher, C.A.B. (Charles), Gomez-Lopez, A. (Arley), Wijngaerden, E. (Eric) van, Ranst, M. (Marc) van, Vercauteren, J. (Jurgen), Vandamme, A.M. (Anne Mieke), and Laethem, K. (Kristel) van

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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6. 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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7. Superinfection with drug-resistant HIV is rare and does not contribute substantially to therapy failure in a large European cohort

Author

Bartha, I. (István), Assel, M. (Matthias), Sloot, P.M.A. (Peter), Zazzi, M. (Maurizio), Torti, C. (Carlo), Schülter, E. (E.), Luca, A. (Angelo), Sonnerborg, A. (Anders), Abecasis, A.B. (Ana), Laethem, K. (Kristel) van, Rosi, A. (Andrea), Svärd, J. (Jenny), Paredes, R. (Roger), Vijver, D.A.M.C. (David) van de, Vandamme, A.M. (Anne Mieke), Müller, V., Bartha, I. (István), Assel, M. (Matthias), Sloot, P.M.A. (Peter), Zazzi, M. (Maurizio), Torti, C. (Carlo), Schülter, E. (E.), Luca, A. (Angelo), Sonnerborg, A. (Anders), Abecasis, A.B. (Ana), Laethem, K. (Kristel) van, Rosi, A. (Andrea), Svärd, J. (Jenny), Paredes, R. (Roger), Vijver, D.A.M.C. (David) van de, Vandamme, A.M. (Anne Mieke), and Müller, V.

Abstract

Background: Superinfection with drug resistant HIV strains could potentially contribute to compromised therapy in patients initially infected with drug-sensitive virus and receiving antiretroviral therapy. To investigate the importance of this potential route to drug resistance, we developed a bioinformatics pipeline to detect superinfection from routinely collected genotyping data, and assessed whether superinfection contributed to increased drug resistance in a large European cohort of viremic, drug treated patients. Methods: We used sequence data from routine genotypic tests spanning the protease and partial reverse transcriptase regions in the Virolab and EuResist databases that collated data from five European countries. Superinfection was indicated when sequences of a patient failed to cluster together in phylogenetic trees constructed with selected sets of control sequences. A subset of the indicated cases was validated by re-sequencing pol and env regions from the original samples. Results: 4425 patients had at least two sequences in the database, with a total of 13816 distinct sequence entries (of which 86% belonged to subtype B). We identified 107 patients with phylogenetic evidence for superinfection. In 14 of these cases, we analyzed newly amplified sequences from the original samples for validation purposes: only 2 cases were verified as superinfections in the repeated analyses, the other 12 cases turned out to involve sample or sequence misidentification. Resistance to drugs used at the time of strain replacement did not change in these two patients. A third case could not be validated by re-sequencing, but was supported as superinfection by an intermediate sequence with high degenerate base pair count within the t

Published
2013
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8. 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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9. 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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10. Comparison of HIV-1 genotypic resistance test interpretation systems in predicting virological outcomes over time

Author

Frentz, D. (Dineke), Boucher, C.A.B. (Charles), Assel, M. (Matthias), Luca, A. (Andrea) de, Fabbiani, M. (Massimiliano), Incardona, F. (Francesca), Libin, P. (Pieter), Manca, N. (Nino), Müller, V. (Viktor), Nualláin, B.O. (Breanndán), Paredes, R. (Roger), Prosperi, M. (Mattia), Quiros-Roldan, E. (Eugenia), Ruiz, L. (Lidia), Sloot, P.M.A. (Peter), Torti, C. (Carlo), Vandamme, A.M. (Anne Mieke), Laethem, K. (Kristel), Zazzi, M. (Maurizio), Vijver, D.A.M.C. (David) van de, Frentz, D. (Dineke), Boucher, C.A.B. (Charles), Assel, M. (Matthias), Luca, A. (Andrea) de, Fabbiani, M. (Massimiliano), Incardona, F. (Francesca), Libin, P. (Pieter), Manca, N. (Nino), Müller, V. (Viktor), Nualláin, B.O. (Breanndán), Paredes, R. (Roger), Prosperi, M. (Mattia), Quiros-Roldan, E. (Eugenia), Ruiz, L. (Lidia), Sloot, P.M.A. (Peter), Torti, C. (Carlo), Vandamme, A.M. (Anne Mieke), Laethem, K. (Kristel), Zazzi, M. (Maurizio), and Vijver, D.A.M.C. (David) van de

Abstract

Background: Several decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford's HIVdb) to predict virological outcome at 12, 24, and 48 weeks. Methodology/Principal Findings: Included were 3763 treatment-change episodes (TCEs) for which a HIV-1 genotype was available at the time of changing treatment with at least one follow-up viral load measurement. Genotypic susceptibility scores for the active regimens were calculated using scores defined by each interpretation system. Using logistic regression, we determined the association between the genotypic susceptibility score and proportion of TCEs having an undetectable viral load (<50 copies/ml) at 12 (8-16) weeks (2152 TCEs), 24 (16-32) weeks (2570 TCEs), and 48 (44-52) weeks (1083 TCEs). The Area under the ROC curve was calculated using a 10-fold cross-validation to compare the different interpretation systems regarding the sensitivity and specificity for predicting undetectable viral load. The mean genotypic susceptibility score of the systems was slightly smaller for HIVdb, with 1.92±1.17, compared to Rega and ANRS, with 2.22±1.09 and 2.23±1.05, respectively. However, similar odds ratio's were found for the association between each-unit increase in genotypic susceptibility score and undetectable viral load at week 12; 1.6 [95% confidence interval 1.5-1.7] for HIVdb, 1.7 [1.5-1.8] for ANRS, and 1.7 [1.9-1.6] for Rega. Odds ratio's increased over time, but remained comparable (odds ratio's ranging between 1.9-2.1 at 24 weeks and 1.9-2.2

Published
2010
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