A highly virulent variant of HIV-1 circulating in the Netherlands

Authors: Chris Wymant, Daniela Bezemer, François Blanquart, Luca Ferretti, Astrid Gall, Matthew Hall, Tanya Golubchik, Margreet Bakker, Swee Hoe Ong, Lele Zhao, David Bonsall, Mariateresa de Cesare, George MacIntyre-Cockett, Lucie Abeler‐Dörner, Jan Albert, Norbert Bannert, Jacques Fellay, M. Kate Grabowski, Barbara Gunsenheimer‐Bartmeyer, Huldrych F. Günthard, Pia Kivelä, Roger D. Kouyos, Oliver Laeyendecker, Laurence Meyer, Kholoud Porter, Matti Ristola, Ard van Sighem, Ben Berkhout, Paul Kellam, Marion Cornelissen, Peter Reiss, Christophe Fraser, the Netherlands ATHENA HIV Observational Cohort†, Vincent Aubert, Manuel Battegay, Enos Bernasconi, Jürg Böni, Dominique L. Braun, H C Bucher, Claudine Burton‐Jeangros, Alexandra Calmy, Matthias Cavassini, G Dollenmaier, Matthias Egger, Luigia Elzi, Jan Fehr, Jacques Fellay, Hansjakob Furrer, Christoph A. Fux, Meri Gorgievski, Huldrych F. Günthard, David Haerry, Barbara Hasse, Hans H. Hirsch, Matthias Hoffmann, Irène Hösli, Christian R. Kahlert, Laurent Kaiser, Olivia Keiser, Thomas Klimkait, Roger D. Kouyos, Helen Kovari, Bruno Ledergerber, G Martinetti, Begoña Martínez de Tejada, Catia Marzolini, Karin J. Metzner, N Müller, David Nadal, Dunja Nicca, G Pantaleo, Andri Rauch, Stephan Regenass, Christoph Rudin, F. Schöni-Affolter, Patrick Schmid, R Speck, M Stöckle, Philip Tarr, Alexandra Trkola, Pietro Vernazza, Rainer Weber, Sabine Yerly, Mark van der Valk, Suzanne E. Geerlings, Abraham Goorhuis, Joppe W. Hovius, B. Lempkes, F.J.B. Nellen, T. van der Poll, Jan M. Prins, Peter Reiss, Michèle van Vugt, W. Joost Wiersinga, F.W.M.N. Wit, Marlies van Duinen, J. van Eden, A. Hazenberg, A M H van Hes, F J J Pijnappel, S Smalhout, Annouschka M. Weijsenfeld, Suzanne Jurriaans, Nicole Back, Hans L. Zaaijer, Ben Berkhout, Marion Cornelissen, C. Schinkel, Katja C. Wolthers, Edgar J.G. Peters, Michiel A. van Agtmael, Reshma Autar, Marije K. Bomers, Kim Sigaloff, M. Heitmuller, Liedewij Laan, C. Wim Ang, Robin van Houdt, Marcel Jonges, TW Kuijpers, Dasja Pajkrt, H. J. Scherpbier, Carla de Boer, A. van der Plas, Maarten van den Berge, Arjan Stegeman, S. Baas, L. Hage de Looff, A. G. M. Buiting, Anne Q. Reuwer, Jacobien Veenemans, Bas Wintermans, M.J.H. Pronk, Heidi Ammerlaan, D. N. J. van den Bersselaar, E.S. de Munnik, Birgit Deiman, A Jansz, Volkher Scharnhorst, Jeroen H. T. Tjhie, M.C.A. Wegdam, Arne van Eeden, Jeannine F. Nellen, W. Brokking, Loek J.M. Elsenburg, H. Nobel, M.E.E. van Kasteren, Marvin A. H. Berrevoets, A.E. Brouwer, Alexander Adams, R. van Erve, B.A.F.M. de Kruijf-van de Wiel, S. Keelan-Phaf, B. van de Ven, B. van der Ven, A. G. M. Buiting, J.L. Murck, T.E.M.S. de Vries-Sluijs, Hannelore I. Bax, Eric C. M. Van Gorp, N. C. de Jong-Peltenburg, Martim Melo, Els van Nood, Jan Nouwen, Bart Rijnders, Casper Rokx, Carolina A. M. Schurink, Lennert Slobbe, Annelies Verbon, N. Bassant, J.E.A. van Beek, M. Vriesde, L.M. van Zonneveld, Joris R. de Groot, Charles A. Boucher, Marion Koopmans, Jeroen J. A. van Kampen, Pieter L. A. Fraaij, Annemarie M. C. van Rossum, Clementien L. Vermont, Linda C. van der Knaap, Eric J. W. Visser, Judith Branger, Renée A. Douma, A.S. Cents-Bosma, C.J.H.M. Duijf-van de Ven, Emile F. Schippers, Cees van Nieuwkoop, J M van IJperen, J. Geilings, G. van der Hut, Nathalie D. van Burgel, Eliane M.S. Leyten, L. B. S. Gelinck, Femke Mollema, S. Davids-Veldhuis, C. Tearno, G.S. Wildenbeest, E. Heikens, P. H. P. Groeneveld, J.W. Bouwhuis, A. J. J. Lammers, S. Kraan, A. G. W. van Hulzen, M.S.M. Kruiper, G.L. van der Bliek, Petra Bor, S. B. Debast, Gertjan H.J. Wagenvoort, Frank P. Kroon, Mark de Boer, H. Jolink, Merel M. C. Lambregts, Anna H.E. Roukens, Henk Scheper, W. Dorama, Natasja van Holten, Eric C. J. Claas, Els Wessels, Jan G. den Hollander, Rachida el Moussaoui, Katalin Pogány, C.J. Brouwer, Jesper Smit, D. Struik-Kalkman, T.G.C.M. van Niekerk, Oscar Pontesilli, S.H. Lowe, Astrid M. L. Oude Lashof, Dirk Posthouwer, Marlies E van Wolfswinkel, Robin Ackens, Kristina Burgers, J. Schippers, B. Weijenberg-Maes, Inge H. M. van Loo, Thomas Havenith, Marit G. A. van Vonderen, Linda M. Kampschreur, S. M. Faber, R. Steeman-Bouma, A. Al Moujahid, G. J. Kootstra, C. E. Delsing, Matthijs Plas, L. Scheiberlich, W. Kortmann, G. van Twillert, R. Renckens, D. Ruiter-Pronk, F.A. van Truijen-Oud, J. W. T. Cohen Stuart, E.R. Jansen, Marieke Hoogewerf, Wouter Rozemeijer, Wil A. van der Reijden, J. C. Sinnige, Kees Brinkman, G.E.L. van den Berk, W. L. Blok, Kamilla D. Lettinga, Marina de Regt, W.E.M. Schouten, Janneke E. Stalenhoef, Jan A. Veenstra, S.M.E. Vrouenraets, H. Blaauw, G.F. Geerders, M.J. Kleene, Marc R. Kok, M. Knapen, I.B. van der Meché, E. Mulder-Seeleman, A.J.M. Toonen, S. Wijnands, E. Wttewaal, David Kwa, Reinout van Crevel, Koen van Aerde, Anthonius S. M. Dofferhoff, S. S. V. Henriet, H.J.M. ter Hofstede, Jacobien J. Hoogerwerf, Monique Keuter, Olivier Richel, M. Albers, K.J.T. Grintjes-Huisman, M. de Haan, M. Marneef, R. Strik-Albers, Janette Rahamat‐Langendoen, Foekje F. Stelma, David M. Burger, Elisabeth H. Gisolf, Robert‐Jan Hassing, Mark A. A. Claassen, G. ter Beest, P.H.M. van Bentum, Nienke Langebeek, R. Tiemessen, C.M.A. Swanink, S.F.L. van Lelyveld, Robert Soetekouw, L.M.M. van der Prijt, J. van der Swaluw, N. Bermon, Wil A. van der Reijden, Ronald Jansen, Bjorn L. Herpers, Dick Veenendaal, D.W.M. Verhagen, Fanny N. Lauw, Michelle Broekhuizen, Michiel P. van Wijk, Wouter F.W. Bierman, Margreet Bakker, Johanneke Kleinnijenhuis, E. Kloeze, Ananja Middel, Douwe F. Postma, Elisabeth H. Schölvinck, Ymkje Stienstra, Adriaan Verhage, Marjan Wouthuyzen‐Bakker, André Boonstra, H. de Jonge, P. A. van der Meulen, D.A. de Weerd, Hubert G.M. Niesters, Coretta van Leer‐Buter, Marjolein Knoester, Andy I. M. Hoepelman, Joop E. Arends, Roos E. Barth, A.H.W. Bruns, Pauline M. Ellerbroek, Tania Mudrikova, Jan Jelrik Oosterheert, E.M. Schadd, Berend J. van Welzen, K. Aarsman, B.M.G. Griffioen-van Santen, I. de Kroon, M. van Berkel, C S A M van Rooijen, Rob Schuurman, F. Verduyn-Lunel, Annemarie M. J. Wensing, Louis Bont, Sibyl P. M. Geelen, Yvette G.T. Loeffen, Tom F.W. Wolfs, N. Nauta, E. O. W. Rooijakkers, H. Holtsema, Rob Voigt, D. van de Wetering, André Justino Alberto, Ingrid van der Meer, A. Rosingh, T. Halaby, S Zaheri, Anders Boyd, Daniela Bezemer, A.I. van Sighem, Colette Smit, M Hillebregt, A. de Jong, T.J. Woudstra, D.P. Bergsma, Roelien A. M. Meijering, Linette Sande, T. Rutkens, Stefan van der Vliet, C.P.G.M. de Groot, Marjan van den Akker, Y. Bakker, A el Berkaoui, M. Bezemer, N.M. Brétin, E.A. Djoechro, M. Groters, E Kruijne, K.J. Lelivelt, C.R.E. Lodewijk, Eric R. Lucas, L. Munjishvili, F. Paling, B Peeck, Cornelis L. P. van de Ree, R. Regtop, Y M C Ruijs, Maartje Schoorl, P.P. Schnörr, A. Scheigrond, E. Tuijn, L. Veenenberg, Kirsten Visser, E.C.M. Witte, Y M C Ruijs, Maartje Van Frankenhuijsen, Thierry Allègre, Djamila Makhloufi, Jean‐Michel Livrozet, Pierre Chiarello, Mathieu Godinot, Florence Brunel-Dalmas, Sylvie Gibert, Christian Trépo, D. Peyramond, Patrick Miailhes, J. Koffi, V. Thoirain, C. Brochier, Thomas Baudry, Sylvie Pailhes, Alain Lafeuillade, Gisèle Philip, Gilles Hittinger, Assi Assi, Véronique Lambry, Eric T. Rosenthal, Alissa Naqvi, Brigitte Dunais, Éric Cua, Christian Pradier, J. Durant, A. Joulié, D. Quinsat, S. Tempesta, Isabelle Ravaux, Isabelle Poizot Martin, Olivia Zaegel‐Faucher, Nicolas Cloarec, Hélène Champagne, Gilles Pichancourt, Philippe Morlat, Thierry Pistone, Fabrice Bonnet, P. Mercié, Isabelle Faure, Mojgan Hessamfar, Denis Malvy, D. Lacoste, Marie-Carmen Pertusa, Marie-Anne Vandenhende, Noëlle Bernard, F. Paccalin, Cédric Martell, Julien Roger-Schmelz, Marie‐Catherine Receveur, P. Duffau, D. Dondia, Emmanuel Ribeiro, Sabrina Caltado, D. Neau, Michel Dupont, Hervé Dutronc, F. Dauchy, Charles Cazanave, Marc-Olivier Vareil, Gaëtane Wirth, Séverine Le Puil, Jean-Luc Pellegrin, Isabelle Raymond‐Letron, Jean‐François Viallard, Severin Chaigne de Lalande, D. Garipuy, Pierre Delobel, Martine Obadia, Lise Cuzin, Muriel Alvarez, Noémie Biezunski, Lydie Porte, Patrice Massip, Alexa Debard, Florence Balsarin, Myriam Lagarrigue, François Prevoteau du Clary, Christian Aquilina, Jacques Reynes, Vincent Baillat, Corinne Merle, Vincent Le Moing, N. Atoui, Alain Makinson, Jean Marc Jacquet, Christina Psomas, Christine Tramoni, Hugues Aumaître, Mathieu Saada, Marie Medus, Martine Malet, A. Eden, Ségolène Neuville, Milagros Ferreyra, Albert Sotto, Claudine Barbuat, Isabelle Rouanet, Didier Leureillard, Jean‐Marc Mauboussin, Catherine Lechiche, Régine Donsesco, André Cabie, Sylvie Abel, Placier Sandrine, Anne-Sophie Batala, Christophe Cerland, Camille Rangom, Nadine Theresine, Bruno Hoën, I. Lamaury, Isabelle Fabre, Kinda Schepers, Elodie Curlier, Rachida Ouissa, C. 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Brewer, Christoph Mayr, Wolfgang Schmidt, Andrea Speidel, Frank Strohbach, Keikawus Arastéh, Christiane Cordes, Manfred Stündel, Jörg Claus, Axel Baumgarten, A Carganico, Patrick Ingiliz, S Dupke, Matthias Freiwald, Michael Rausch, A Moll, Dorothea Schleehauf, B Hintsche, Gerd Klausen, Heiko Jessen, Arne Jessen, Siegfried Köppe, P. Kreckel, Dietmar Schranz, Klaus Fischer, Hubert Schulbin, Miriam Speer, Tobias Glaunsinger, Thomas Wicke, B Bieniek, Heribert Hillenbrand, Frank Schlote, Elke Lauenroth-Mai, Christoph Schuler, Dirk Schürmann, Hans Wesselmann, Norbert H. Brockmeyer, P. M. Gehring, Dirk Schmalöer, Martin Hower, Petra Spornraft‐Ragaller, Dieter Häussinger, Stefan Reuter, Stefan Eßer, M. Rudolf, Burkhard Kreft, Dirk Berzow, Andreas Christl, Andreas L. S. 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increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.