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1. P16-48. Immunologic and virologic characterization of an ART-treated HIV-1 patients cohort with long-term control of viremia

Author: Harari A, Johnson A, Stauss H, Carroll A, Byrne P, Yerly S, Cellerai C, Kinloch S, and Pantaleo G
Subjects: Immunologic diseases. Allergy, RC581-607
Published: 2009
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2. P16-32. Antigen exposure regulates the balance between proliferating and cytotoxic subsets of virus-specific CD8 T-cells

Author: Harari A, Pantaleo G, Bart P, Enders F, Rozot V, Perreau M, and Cellerai C
Subjects: Immunologic diseases. Allergy, RC581-607
Published: 2009
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3. Performance evaluation of a new fourth-generation HIV combination antigen–antibody assay

Author: Mühlbacher, A., Schennach, H., van Helden, J., Hebell, T., Pantaleo, G., Bürgisser, P., Cellerai, C., Permpikul, P., Rodriguez, M. I., Eiras, A., Alborino, F., Cunningham, P., Axelsson, M., Andersson, S., Wetlitzky, O., Kaiser, C., Möller, P., and de Sousa, G.
Published: 2013
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4. WT1 peptide vaccination in poor risk adult AML patients induces WT1-specific immune responses: Results of a leukaemia research supported phase I clinical trial, WTPV-001: 31

Author: Morris, E C, Martinez-Davila, I, Cellerai, C, Chen, F, Moss, P, Khwaja, A, Virchis, A, Kottaridis, P, and Stauss, H J
Published: 2010

5. Non-AIDS defining cancers in the D:A:D Study--time trends and predictors of survival: a cohort study

Author: Worm, S, Bower, M, Reiss, P, Bonnet, F, Law, M, Fätkenheuer, G, d'Arminio Monforte, A, Abrams, D, Grulich, A, Fontas, E, Kirk, O, Furrer, H, Wit, S, Phillips, A, Lundgren, J, Sabin, C, Butcher, D, Delforge, M, Fanti, I, Franquet, X, Geffard, S, Gras, L, Helweg Larsen, J, Hillebregt, M, Kamara, D, Kjær, J, Krum, E, McManus, H, Meidahl, P, Mocroft, A, Nielsen, J, Powderl, W, Rickenbach, M, Rode, R, Ryom, L, Salbøl Brandt, R, Schmidt Iversen, J, Shortman, N, Sjøl, A, Smith, C, Torres, F, Tverland, J, Wright, S, Zaheri, S, de Wolf, F, Smidt, J, Ristola, M, Katlama, C, Viard, J, Girard, P, Livrozet, J, Vanhems, P, Pradier, C, Dabis, F, Neau, D, Rockstroh, J, Schmidt, R, Degen, O, van Lunzen, J, Stellbrink, H, Staszewski, S, Bogner, J, Gargalianos, P, Kosmidis, J, Perdios, J, Xylomenos, G, Filandras, A, Karabatsaki, E, Panos, G, Sambatakou, H, Banhegyi, D, Mulcahy, F, Burke, M, Turner, D, Yust, I, Hassoun, G, Pollack, S, Maayan, S, Vella, S, Esposito, R, Mazeu, I, Mussini, C, Arici, C, Pristera, R, Gabbuti, A, Mazzotta, F, Lichtner, M, Vullo, V, Boer, K, Geerlings, S, Godfried, M, Kuijpers, T, Lange, J, Nellen, F, Pajkrt, D, Prins, J, Scherpbier, H, Vrouenraets, S, Wit, F, van Vugt, M, van der Meer, J, van der Poll, T, van der Valk, M, Chirianni, A, Gargiulo, M, Montesarchio, E, Antonucci, G, Narciso, P, Testa, A, Vlassi, C, Zaccarelli, M, Castagna, A, Gianotti, N, Lazzarin, A, Galli, M, Ridolfo, A, Rozentale, B, Zeltina, I, Chaplinskas, S, Hemmer, R, Staub, T, Bruun, J, Maeland, A, Ormaasen, V, Lowe, S, Oude Lashof, A, Schreij, G, Gasiorowski, J, Knysz, B, Bakowska, E, Horban, A, Flisiak, R, Grzeszczuk, A, Boron Kaczmarska, A, Parczewski, M, Pynka, M, Beniowski, M, Mularska, E, Trocha, H, Jablonowska, E, Malolepsza, E, Wojcik, K, Antunes, F, Caldeira, L, Doroana, M, Mansinho, K, Maltez, F, Bravenboer, B, Pronk, M, Duiculescu, D, Rakhmanova, A, Zakharova, N, Buzunova, S, Jevtovic, D, Mokráš, M, Staneková, D, Tomazic, J, González Lahoz, J, Labarga, P, Medrano, J, Soriano, V, Moreno, S, Rodriguez, J, Bravo, I, Clotet, B, Jou, A, Paredes, R, Puig, J, Tural, C, Gelinck, L, Nouwen, J, Rijnders, B, Schurink, C, Slobbe, L, Verbon, A, de Vries Sluijs, T, van der Ende, M, van der Feltz, M, Gatell, J, Miró, J, Domingo, P, Gutierrez, M, Mateo, G, Sambeat, M, Karlsson, A, Flamholc, L, Ledergerber, B, Weber, R, Cavassini, M, Francioli, P, Boffi, E, Hirschel, B, Battegay, M, Elzi, L, Chentsova, N, Kravchenko, E, Driessen, G, Hartwig, N, Frolov, V, Kutsyna, G, Servitskiy, S, Krasnov, M, Barton, S, Johnson, A, Mercey, D, Johnson, M, Murphy, M, Scullard, G, Weber, J, Fisher, M, Leen, C, Branger, J, Åkerlund, B, Morfeldt, L, S.u.n.d.s.t.r.ö.m. , A, Thulin, G, Koppel, K, Ho̊kangård, C, Angarano, G, Antinori, A, Armignacco, O, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Moroni, M, Perno, C, Viale, P, Von Schlosser, F, Ammassari, A, Andreoni, M, Balotta, C, Bonfanti, P, Bonora, S, Borderi, M, Capobianchi, M, Ceccherini Silberstein, F, Cinque, P, Cozzi Lepri, A, De Luca, A, Gervasoni, C, Girardi, E, Guaraldi, G, Lo Caputo, S, Madeddu, G, Maggiolo, F, Marchetti, G, Marcotullio, S, Monno, L, Murri, R, Puoti, M, Torti, C, Cicconi, P, Formenti, T, Galli, L, Lorenzini, P, Costantini, A, Giacometti, A, Riva, A, Carrisa, C, Lazzari, G, Verucchi, G, Kauffmann, R, Schippers, E, Minardi, C, Abeli, C, Quirino, T, Manconi, P, Piano, P, Falasca, K, Vecchiet, J, Segala, D, Sighinolfi, L, Alessandrini, A, Cassola, G, Mazzarello, G, Piscopo, R, Viscoli, G, Belvisi, V, Mastroianni, C, Caramma, I, Castelli, P, Chiodera, A, Alleman, M, Bouwhuis, J, Groeneveld, P, Bigoloni, A, Carenzi, L, Galli, A, Moioli, M, Piolini, R, Rizzardini, G, Rossotti, R, Salpietro, S, Spagnuolo, V, Zucchi, P, Bisio, L, Gori, A, Lapadula, G, Abrescia, N, Guida, M, Baldelli, F, Belfiori, B, Parruti, G, Ursini, T, Magnani, G, Ursitti, M, Acinapura, R, Capozzi, M, Gallo, L, Libertone, R, Nicastro, E, Tebano, G, Tozzi, V, d'Avino, A, Mura, M, Caramello, P, Orofino, G, Sciandra, M, Soetekouw, R, ten Kate, R, Manfrin, V, Pellizzer, G, Bernard, E, Caissotti, C, Cua, E, De Salvador Guillouet, F, Dellamonica, P, Dollet, K, Durant, J, Ferrando, S, Mondain Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost Keller, B, Pugliese, P, Rahelinirina, V, Roger, P, Barth, J, Bernasconi, E, Böni, J, Bucher, H, Burton Jeangros, C, Calmy, A, Cellerai, C, Dubs, R, Egger, M, Fehr, J, Flepp, M, Fux, C, Gorgievski, M, Günthard, H, Hasse, B, Hirsch, H, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Kind, C, Klimkait, T, Kovari, H, Martinetti, G, Martinez de Tejada, B, Müller, N, Nadal, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schmid, P, Schöni Affolter, F, Schüpbach, J, Schultze, D, Speck, R, Taffé, P, Telenti, A, Trkola, A, Vernazza, P, Yerly, S, von Wyl, V, Arend, S, Jolink, H, Kroon, F, de Boer, M, van Dissel, J, van Nieuwkoop, C, van den Broek, P, Pogany, K, den Hollander, J, Kortmann, W, van Twillert, G, Leyten, E, Vriesendorp, R, Kootstra, G, ten Napel, C, Blok, W, Brinkman, K, Frissen, P, Schouten, W, van den Berk, G, Brouwer, A, Juttmann, J, van Kasteren, M, Lettinga, K, Veenstra, J, Mulder, J, Smit, P, Weijer, S, van Gorp, E, Verhagen, D, van Eeden, A, Doedens, R, Scholvinck, E, Sprenger, H, Stek, C, van Assen, S, Dofferhoff, A, Keuter, M, Koopmans, P, de Groot, R, ter Hofstede, H, van der Flier, M, van der Ven, A, Arends, J, Ellerbroek, P, Hoepelman, A, Jaspers, C, Maarschalk Ellerbroek, L, Mudrikova, T, Oosterheert, J, Peters, E, Schneider, M, Wassenberg, M, van der Hilst, J, Bierman, W, Claessen, F, Danner, S, Perenboom, R, bij de Vaate, E, de Jong, E, de Vocht, J, van Agtmael, M, Geelen, S, Wolfs, T, Gisolf, E, Richter, J, van der Berg, C, Stegeman, A, van den Berge, M, Polée, M, van Houte, D, van Vonderen, M, Duits, A, Winkel, C, Chêne, G, Dupon, M, Fleury, H, Lacoste, D, Malvy, D, Mercié, P, Morlat, P, Pellegrin, I, Pellegrin, J, Thiébaut, R, Titier, K, Bruyand, M, Lawson Ayayi, S, Wittkop, L, Bernard, N, Bonnal, F, Caunègre, L, Cazanave, C, Ceccaldi, J, Chambon, D, Chossat, I, Courtaud, K, Dauchy, F, De Witte, S, Duffau, P, Dupont, A, Dutronc, H, Farbos, S, Gaboriau, V, Gemain, M, Gerard, Y, Greib, C, Hessamfar, M, Lafarie Castet, S, Lataste, P, Lazaro, E, Longy Boursier, M, Meraud, J, Monlun, E, Ochoa, A, Pistone, T, Ragnaud, J, Receveur, M, Roger Schmeltz, J, Tchamgoué, S, Thibaut, P, Vandenhende, M, Viallard, J, Moreau, J, P.e.l.l.e.g.r.i.n. , I, Lafon, M, Masquelier, B, Trimoulet, P, Breilh, D, Haramburu, F, Miremont Salamé, G, Blaizeau, M, D'Ivernois, C, Decoin, M, Delaune, J, Delveaux, S, Hanappier, C, Leleux, O, Sicard, X, Uwamaliya Nziyumvira, B, Leray, J, Palmer, G, Touchard, D, Baker, D, Bendall, C, Bloch, M, Carr, A, Cooper, D, Franic, T, Petoumenos, K, Vale, R, Edwards, S, Hoy, J, Moore, R, Nicholson, J, Roth, N, Watson, K, Chuah, J, Ngieng, M, Nolan, D, Skett, J, Cadafalch, J, Calvo, G, Codina, C, Del Cacho, E, Fuster, M, Mateu, S, Sirera, G, Vaqué, A, Clumeck, N, De Wit, S, Gennotte, A, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Necsoi, C, Payen, M, Semaille, P, Van Laethem, Y, Bartsch, G, El Sadr, W, Neaton, J, Thompson, G, Wentworth, D, Luskin Hawk, R, Telzak, E, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, L, Sampson, J, Baxter, J, Fischer, A, Grint, D, Kjaer, J, Kowalska, J, Peters, L, Podlekareva, D, Reekie, J, Elias, C, Losso, M, Vetter, N, Zangerle, R, Karpov, I, Vassilenko, A, Mitsura, V, Suetnov, O, Colebunders, R, Vandekerckhove, L, Hadziosmanovic, V, Kostov, K, Begovac, J, Jilich, D, Machala, L, Sedlacek, D, Benfield, T, Kronborg, G, Larsen, M, Gerstoft, J, Hansen, A, Katzenstein, T, Skinhøj, P, Pedersen, C, Ostergaard, L, Zilmer, K, Gori, A., GORI, ANDREA, Groupement de Recherche et d'Etudes en Gestion à HEC (GREGH), Ecole des Hautes Etudes Commerciales (HEC Paris)-Centre National de la Recherche Scientifique (CNRS), Department of Pediatrics, Fairview-University Medical Center, Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Observatoire des Micro et Nano Technologies (OMNT - UMS 2920), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Paris 1 Panthéon-Sorbonne - UFR d'Économie (UP1 UFR02), Université Paris 1 Panthéon-Sorbonne (UP1), Laboratory, Royal GD [Deventer], Economics, Umeå University, Research Department of Infection and Population Health [London], University College of London [London] (UCL), Clinicum, Department of Medicine, Infektiosairauksien yksikkö, Worm, S, Bower, M, Reiss, P, Bonnet, F, Law, M, Fätkenheuer, G, d'Arminio Monforte, A, Abrams, D, Grulich, A, Fontas, E, Kirk, O, Furrer, H, Wit, S, Phillips, A, Lundgren, J, Sabin, C, Butcher, D, Delforge, M, Fanti, I, Franquet, X, Geffard, S, Gras, L, Helweg Larsen, J, Hillebregt, M, Kamara, D, Kjær, J, Krum, E, Mcmanus, H, Meidahl, P, Mocroft, A, Nielsen, J, Powderl, W, Rickenbach, M, Rode, R, Ryom, L, Salbøl Brandt, R, Schmidt Iversen, J, Shortman, N, Sjøl, A, Smith, C, Torres, F, Tverland, J, Wright, S, Zaheri, S, de Wolf, F, Smidt, J, Ristola, M, Katlama, C, Viard, J, Girard, P, Livrozet, J, Vanhems, P, Pradier, C, Dabis, F, Neau, D, Rockstroh, J, Schmidt, R, Degen, O, van Lunzen, J, Stellbrink, H, Staszewski, S, Bogner, J, Gargalianos, P, Kosmidis, J, Perdios, J, Xylomenos, G, Filandras, A, Karabatsaki, E, Panos, G, Sambatakou, H, Banhegyi, D, Mulcahy, F, Burke, M, Turner, D, Yust, I, Hassoun, G, Pollack, S, Maayan, S, Vella, S, Esposito, R, Mazeu, I, Mussini, C, Arici, C, Pristera, R, Gabbuti, A, Mazzotta, F, Lichtner, M, Vullo, V, Boer, K, Geerlings, S, Godfried, M, Kuijpers, T, Lange, J, Nellen, F, Pajkrt, D, Prins, J, Scherpbier, H, Vrouenraets, S, Wit, F, van Vugt, M, van der Meer, J, van der Poll, T, van der Valk, M, Chirianni, A, Gargiulo, M, Montesarchio, E, Antonucci, G, Narciso, P, Testa, A, Vlassi, C, Zaccarelli, M, Castagna, A, Gianotti, N, Lazzarin, A, Galli, M, Ridolfo, A, Rozentale, B, Zeltina, I, Chaplinskas, S, Hemmer, R, Staub, T, Bruun, J, Maeland, A, Ormaasen, V, Lowe, S, Oude Lashof, A, Schreij, G, Gasiorowski, J, Knysz, B, Bakowska, E, Horban, A, Flisiak, R, Grzeszczuk, A, Boron Kaczmarska, A, Parczewski, M, Pynka, M, Beniowski, M, Mularska, E, Trocha, H, Jablonowska, E, Malolepsza, E, Wojcik, K, Antunes, F, Caldeira, L, Doroana, M, Mansinho, K, Maltez, F, Bravenboer, B, Pronk, M, Duiculescu, D, Rakhmanova, A, Zakharova, N, Buzunova, S, Jevtovic, D, Mokráš, M, Staneková, D, Tomazic, J, González Lahoz, J, Labarga, P, Medrano, J, Soriano, V, Moreno, S, Rodriguez, J, Bravo, I, Clotet, B, Jou, A, Paredes, R, Puig, J, Tural, C, Gelinck, L, Nouwen, J, Rijnders, B, Schurink, C, Slobbe, L, Verbon, A, de Vries Sluijs, T, van der Ende, M, van der Feltz, M, Gatell, J, Miró, J, Domingo, P, Gutierrez, M, Mateo, G, Sambeat, M, Karlsson, A, Flamholc, L, Ledergerber, B, Weber, R, Cavassini, M, Francioli, P, Boffi, E, Hirschel, B, Battegay, M, Elzi, L, Chentsova, N, Kravchenko, E, Driessen, G, Hartwig, N, Frolov, V, Kutsyna, G, Servitskiy, S, Krasnov, M, Barton, S, Johnson, A, Mercey, D, Johnson, M, Murphy, M, Scullard, G, Weber, J, Fisher, M, Leen, C, Branger, J, Åkerlund, B, Morfeldt, L, S. u. n. d. s. t. r. ö. m., A, Thulin, G, Koppel, K, Ho̊kangård, C, Angarano, G, Antinori, A, Armignacco, O, Castelli, F, Cauda, R, Di Perri, G, Iardino, R, Ippolito, G, Moroni, M, Perno, C, Viale, P, Von Schlosser, F, Ammassari, A, Andreoni, M, Balotta, C, Bonfanti, P, Bonora, S, Borderi, M, Capobianchi, M, Ceccherini Silberstein, F, Cinque, P, Cozzi Lepri, A, De Luca, A, Gervasoni, C, Girardi, E, Gori, A, Guaraldi, G, Lo Caputo, S, Madeddu, G, Maggiolo, F, Marchetti, G, Marcotullio, S, Monno, L, Murri, R, Puoti, M, Torti, C, Cicconi, P, Formenti, T, Galli, L, Lorenzini, P, Costantini, A, Giacometti, A, Riva, A, Carrisa, C, Lazzari, G, Verucchi, G, Kauffmann, R, Schippers, E, Minardi, C, Abeli, C, Quirino, T, Manconi, P, Piano, P, Falasca, K, Vecchiet, J, Segala, D, Sighinolfi, L, Alessandrini, A, Cassola, G, Mazzarello, G, Piscopo, R, Viscoli, G, Belvisi, V, Mastroianni, C, Caramma, I, Castelli, P, Chiodera, A, Alleman, M, Bouwhuis, J, Groeneveld, P, Bigoloni, A, Carenzi, L, Galli, A, Moioli, M, Piolini, R, Rizzardini, G, Rossotti, R, Salpietro, S, Spagnuolo, V, Zucchi, P, Bisio, L, Lapadula, G, Abrescia, N, Guida, M, Baldelli, F, Belfiori, B, Parruti, G, Ursini, T, Magnani, G, Ursitti, M, Acinapura, R, Capozzi, M, Gallo, L, Libertone, R, Nicastro, E, Tebano, G, Tozzi, V, D'Avino, A, Mura, M, Caramello, P, Orofino, G, Sciandra, M, Soetekouw, R, ten Kate, R, Manfrin, V, Pellizzer, G, Bernard, E, Caissotti, C, Cua, E, De Salvador Guillouet, F, Dellamonica, P, Dollet, K, Durant, J, Ferrando, S, Mondain Miton, V, Naqvi, A, Perbost, I, Pillet, S, Prouvost Keller, B, Pugliese, P, Rahelinirina, V, Roger, P, Barth, J, Bernasconi, E, Böni, J, Bucher, H, Burton Jeangros, C, Calmy, A, Cellerai, C, Dubs, R, Egger, M, Fehr, J, Flepp, M, Fux, C, Gorgievski, M, Günthard, H, Hasse, B, Hirsch, H, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Kind, C, Klimkait, T, Kovari, H, Martinetti, G, Martinez de Tejada, B, Müller, N, Nadal, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schmid, P, Schöni Affolter, F, Schüpbach, J, Schultze, D, Speck, R, Taffé, P, Telenti, A, Trkola, A, Vernazza, P, Yerly, S, von Wyl, V, Arend, S, Jolink, H, Kroon, F, de Boer, M, van Dissel, J, van Nieuwkoop, C, van den Broek, P, Pogany, K, den Hollander, J, Kortmann, W, van Twillert, G, Leyten, E, Vriesendorp, R, Kootstra, G, ten Napel, C, Blok, W, Brinkman, K, Frissen, P, Schouten, W, van den Berk, G, Brouwer, A, Juttmann, J, van Kasteren, M, Lettinga, K, Veenstra, J, Mulder, J, Smit, P, Weijer, S, van Gorp, E, Verhagen, D, van Eeden, A, Doedens, R, Scholvinck, E, Sprenger, H, Stek, C, van Assen, S, Dofferhoff, A, Keuter, M, Koopmans, P, de Groot, R, ter Hofstede, H, van der Flier, M, van der Ven, A, Arends, J, Ellerbroek, P, Hoepelman, A, Jaspers, C, Maarschalk Ellerbroek, L, Mudrikova, T, Oosterheert, J, Peters, E, Schneider, M, Wassenberg, M, van der Hilst, J, Bierman, W, Claessen, F, Danner, S, Perenboom, R, bij de Vaate, E, de Jong, E, de Vocht, J, van Agtmael, M, Geelen, S, Wolfs, T, Gisolf, E, Richter, J, van der Berg, C, Stegeman, A, van den Berge, M, Polée, M, van Houte, D, van Vonderen, M, Duits, A, Winkel, C, Chêne, G, Dupon, M, Fleury, H, Lacoste, D, Malvy, D, Mercié, P, Morlat, P, Pellegrin, I, Pellegrin, J, Thiébaut, R, Titier, K, Bruyand, M, Lawson Ayayi, S, Wittkop, L, Bernard, N, Bonnal, F, Caunègre, L, Cazanave, C, Ceccaldi, J, Chambon, D, Chossat, I, Courtaud, K, Dauchy, F, De Witte, S, Duffau, P, Dupont, A, Dutronc, H, Farbos, S, Gaboriau, V, Gemain, M, Gerard, Y, Greib, C, Hessamfar, M, Lafarie Castet, S, Lataste, P, Lazaro, E, Longy Boursier, M, Meraud, J, Monlun, E, Ochoa, A, Pistone, T, Ragnaud, J, Receveur, M, Roger Schmeltz, J, Tchamgoué, S, Thibaut, P, Vandenhende, M, Viallard, J, Moreau, J, P. e. l. l. e. g. r. i. n., I, Lafon, M, Masquelier, B, Trimoulet, P, Breilh, D, Haramburu, F, Miremont Salamé, G, Blaizeau, M, D'Ivernois, C, Decoin, M, Delaune, J, Delveaux, S, Hanappier, C, Leleux, O, Sicard, X, Uwamaliya Nziyumvira, B, Leray, J, Palmer, G, Touchard, D, Baker, D, Bendall, C, Bloch, M, Carr, A, Cooper, D, Franic, T, Petoumenos, K, Vale, R, Edwards, S, Hoy, J, Moore, R, Nicholson, J, Roth, N, Watson, K, Chuah, J, Ngieng, M, Nolan, D, Skett, J, Cadafalch, J, Calvo, G, Codina, C, Del Cacho, E, Fuster, M, Mateu, S, Sirera, G, Vaqué, A, Clumeck, N, De Wit, S, Gennotte, A, Gerard, M, Kabeya, K, Konopnicki, D, Libois, A, Martin, C, Necsoi, C, Payen, M, Semaille, P, Van Laethem, Y, Bartsch, G, El Sadr, W, Neaton, J, Thompson, G, Wentworth, D, Luskin Hawk, R, Telzak, E, Cohn, D, Markowitz, N, Arduino, R, Mushatt, D, Friedland, G, Perez, G, Tedaldi, E, Fisher, E, Gordin, F, Crane, L, Sampson, J, Baxter, J, Fischer, A, Grint, D, Kjaer, J, Kowalska, J, Peters, L, Podlekareva, D, Reekie, J, Elias, C, Losso, M, Vetter, N, Zangerle, R, Karpov, I, Vassilenko, A, Mitsura, V, Suetnov, O, Colebunders, R, Vandekerckhove, L, Hadziosmanovic, V, Kostov, K, Begovac, J, Jilich, D, Machala, L, Sedlacek, D, Benfield, T, Kronborg, G, Larsen, M, Gerstoft, J, Hansen, A, Katzenstein, T, Skinhøj, P, Pedersen, C, Ostergaard, L, Zilmer, K, Internal medicine, Pediatric surgery, Plastic, Reconstructive and Hand Surgery, CCA - Innovative therapy, IOO, Worm, Signe W., Bower, Mark, Reiss, Peter, Bonnet, Fabrice, Law, Matthew, Fã¤tkenheuer, Gerd, D'arminio Monforte, Antonella, Abrams, Donald I., Grulich, Andrew, Fontas, Eric, Kirk, Ole, Furrer, Hansjakob, Wit, Stephane D., Phillips, Andrew, Lundgren, Jens D., Sabin, Caroline A., D:A:D Study, Group, Experimental Psychology, Groningen Research Institute for Asthma and COPD (GRIAC), Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Global Health, Other departments, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, Other Research, Obstetrics and Gynaecology, General Internal Medicine, Center of Experimental and Molecular Medicine, Medical Microbiology and Infection Prevention, Institut Nanosciences et Cryogénie (INAC), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Kaplan Meier method, proportional hazards model, SWISS HIV COHORT, HIV Infections, 0302 clinical medicine, 1108 Medical Microbiology, cancer diagnosis, Prospective Studies, Pathologie maladies infectieuses, cancer survival, ComputingMilieux_MISCELLANEOUS, IMMUNODEFICIENCY, Incidence, Sciences bio-médicales et agricoles, cohort analysis, Prognosis, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, D:A:D Study Group, risk factor, 030220 oncology & carcinogenesis, Cohort, Cohort study, prospective study, Human, medicine.medical_specialty, Prognosi, HIV, Non-AIDS defining cancers, Trends, Adult, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Female, Humans, Kaplan-Meier Estimate, Middle Aged, Neoplasms, Infectious Diseases, non AIDS defining cancer, Microbiology, cancer prognosis, 03 medical and health sciences, death, Anal cancer, Risk factor, Proportional hazards model, HIV Infections -- drug therapy -- mortality, Anti-HIV Agent, Anti-HIV Agents/therapeutic use, Antiretroviral Therapy, HIV Infections/drug therapy/ mortality, medicine.disease, major clinical study, mortality, Prospective Studie, age, Neoplasms -- mortality, observational study, cancer incidence, anus cancer, gender, Trend, Medicine and Health Sciences, HIV Infection, 030212 general & internal medicine, Prospective cohort study, survival prediction, RISK, INFECTED PATIENTS, ACTIVE ANTIRETROVIRAL THERAPY, Incidence (epidemiology), article, Human immunodeficiency virus infected patient, ANAL CANCER, Non-AIDS defining cancer, Anti-HIV Agents -- therapeutic use, ethnicity, 0605 Microbiology, Research Article, Hodgkin disease, UNITED-STATES, 610 Medicine & health, smoking, NO, MALIGNANCIES, Internal medicine, mental disorders, medicine, follow up, Highly Active, controlled study, Lung cancer, HODGKINS-DISEASE, disseminated cancer, business.industry, 1103 Clinical Sciences, BONE-MARROW-TRANSPLANTATION, Surgery, lung cancer, 3121 General medicine, internal medicine and other clinical medicine, Neoplasm, business
Abstract: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2013
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6. Short- and long-term mortality and causes of death in HIV/tuberculosis patients in Europe

Author: Podlekareva, D. N., Panteleev, A. M., Grint, D., Post, F. A., Miro, J. M., Bruyand, M., Furrer, H., Obel, N., Girardi, E., Vasilenko, A., Losso, M. H., Arenas-Pinto, A., Cayla, J., Rakhmanova, A., Zeltina, I., Werlinrud, A. M., Lundgren, J. D., Mocroft, A., Kirk, O., Toibaro, J. J., Warley, E., Tamayo, N., Cristina Ortiz, M., Scapelatto, P., Bottaro, E., Murano, F., Miachans, M., Contarelli, J., Massera, L., Corral, J., Hualde, M., Miglioranza, C., Corti, M., Metta, H., Casiro, A., Cuini, R., Laplume, H., David, D., Marson, C., Lupo, S., Trape, L., Garcia Messina, O., Gear, O., Bruguera, J. M., Karpov, I., Skrahina, E., Skrahin, A., Mitsura, V., Kozorez, E., Ruzanov, D., Bondarenko, V., Suetnov, O., Paduto, D., Dabis, F., Matteelli, A., Carvalho, A. C., Basche, R., Hamad, I. E., Ricci, B. A., Maggiolo, F., Ravasio, V., Mussini, C., Prati, F., Castelletti, S., Spallanzani, L., Antinori, A., Antonucci, G., Bibbolino, C., Bove, G., Busi Rizzi, E., Cicalini, S., Conte, A., Cuzzi, G., De Mori, P., Festa, A., Goletti, D., Grisetti, S., Gualano, G., Lauria, F. N., Maddaluno, R., Migliorisi Ramazzini, P., Narciso, P., Parracino, L., Palmieri, F., Petrosillo, N., Pucillo, L., Puro, V., Vanacore, P., Urso, R., d'Arminio Monforte, A., Riekstina, V., Aldins, P., Duiculescu, D., Malashenkov, E., Kozlov, A., Buzunova, S., Manzardo, C., Garcia-Goez, J. F., Moreno-Camacho, A., Martinez, J. A., Gonzalez, J., Garcia-Alcaide, F., Perez, I., Gatell, J. M., Sanchez, P., Lopez-Colomes, J. L., Martinez-Lacasa, X., Falco, V., Imaz, A., Ocana, I., Vidal, R., Sambeat, M. A., Moreno-Martinez, A., Millet, J. P., Fina, L., del Bano, L., Orcau, A., Barth, J., Battegay, M., Bernasconi, E., Boni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hirschel, B., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Campbell, L., Miller, R., Chentsova, N., Podlekareva, D., Kjaer, J., and Duiculesku, D.
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Multivariate analysis, Tuberculosis, Anti-HIV Agents, Antitubercular Agents, Argentina, HIV Infections, Rate ratio, Cohort Studies, symbols.namesake, Cause of Death, Coinfection, Europe, Female, Humans, Multivariate Analysis, Internal medicine, medicine, Poisson regression, Cause of death, business.industry, Mortality rate, medicine.disease, 3. Good health, Surgery, Cohort, symbols, business, Cohort study
Abstract: Mortality of HIV/tuberculosis (TB) patients in Eastern Europe is high. Little is known about their causes of death. This study aimed to assess and compare mortality rates and cause of death in HIV/TB patients across Eastern Europe and Western Europe and Argentina (WEA) in an international cohort study. Mortality rates and causes of death were analysed by time from TB diagnosis (3 months, 3-12 months or12 months) in 1078 consecutive HIV/TB patients. Factors associated with TB-related death were examined in multivariate Poisson regression analysis. 347 patients died during 2625 person-years of follow-up. Mortality in Eastern Europe was three- to ninefold higher than in WEA. TB was the main cause of death in Eastern Europe in 80%, 66% and 61% of patients who died3 months, 3-12 months or12 months after TB diagnosis, compared to 50%, 0% and 15% in the same time periods in WEA (p0.0001). In multivariate analysis, follow-up in WEA (incidence rate ratio (IRR) 0.12, 95% CI 0.04-0.35), standard TB-treatment (IRR 0.45, 95% CI 0.20-0.99) and antiretroviral therapy (IRR 0.32, 95% CI 0.14-0.77) were associated with reduced risk of TB-related death. Persistently higher mortality rates were observed in HIV/TB patients in Eastern Europe, and TB was the dominant cause of death at any time during follow-up. This has important implications for HIV/TB programmes aiming to optimise the management of HIV/TB patients and limit TB-associated mortality in this region.
Published: 2014

7. Health care index score and risk of death following tuberculosis diagnosis in HIV-positive patients

Author: Podlekareva, D. N., Grint, D., Post, F. A., Mocroft, A., Panteleev, A. M., Miller, R. F., Miro, J. M., Bruyand, M., Furrer, H., Riekstina, V., Girardi, E., Losso, M. H., Cayla, J. A., Malashenkov, E. A., Obel, N., Skrahina, A. M., Lundgren, J. D., Kirk, O., Chentsova, N., Duiculesku, D., Toibaro, J. J., Warley, E., Tamayo, N., Ortiz, M. C., Scapelatto, P., Bottaro, E., Murano, F., Miachans, M., Contarelli, J., Massera, L., Corral, J., Hualde, M., Miglioranza, C., Corti, M., Metta, H., Casiro, A., Cuini, R., Laplume, H., David, D., Marson, C., Lupo, S., Trape, L., Garcia Messina, O., Gear, O., Bruguera, J. M., Karpov, I., Vasilenko, A., Skrahina, E., Mitsura, V., Kozorez, E., Ruzanov, D., Bondarenko, V., Suetnov, O., Paduto, D., Dabis, F., Matteelli, A., Carvalho, A. C., Basche, R., Hamad, I. E., Ricci, B. A., Maggiolo, F., Ravasio, V., Mussini, C., Prati, F., Castelletti, S., Spallanzani, L., Antinori, A., Antonucci, G., Bibbolino, C., Bove, G., Busi Rizzi, E., Cicalini, S., Conte, A., Cuzzi, G., De Mori, P., Festa, A., Goletti, D., Grisetti, S., Gualano, G., Lauria, F. N., Maddaluno, R., Migliorisi Ramazzini, P., Narciso, P., Parracino, L., Palmieri, F., Petrosillo, N., Pucillo, L., Puro, V., Vanacore, P., Urso, R., Aldins, P., Zeltina, I., Duiculescu, D., Rakhmanova, A., Kozlov, A., Buzunova, S., Manzardo, C., Garcia-Goez, J. F., Moreno-Camacho, A., Martinez, J. A., Gonzalez, J., Garcia-Alcaide, F., Perez, I., Gatell, J. M., Sanchez, P., Lopez-Colomes Mutua de Terrassa, J. L., Martinez-Lacasa, X., Imaz, V. F., Ocana, I., Vidal, R., Sambeat, M. A., Moreno-Martinez, A., Millet, J. P., Fina, L., del Bano, L., Orcau, A., Barth, J., Battegay, M., Bernasconi, E., Boni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Fux, C. A., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. H., Hirschel, B., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Campbell, L., Arenas-Pinto, A., Kjaer, J., and Ellefson, M.
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, medicine.medical_specialty, Tuberculosis, TB-HIV co-infection, Health care index score, Outcome of TB-HIV patients, TB-HIV health care utilisation, AIDS-Related Opportunistic Infections, Cause of Death, Coinfection, Delivery of Health Care, Female, Follow-Up Studies, Global Health, HIV Seropositivity, Humans, Proportional Hazards Models, Retrospective Studies, Risk Assessment, Risk Factors, Severity of Illness Index, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Severity of illness, Health care, medicine, 030212 general & internal medicine, Cause of death, business.industry, Proportional hazards model, Retrospective cohort study, medicine.disease, 3. Good health, Surgery, Regimen, Infectious Diseases, Risk assessment, business
Abstract: OBJECTIVES: To assess health care utilisation for patients co-infected with TB and HIV (TB-HIV), and to develop a weighted health care index (HCI) score based on commonly used interventions and compare it with patient outcome. METHODS: A total of 1061 HIV patients diagnosed with TB in four regions, Central/Northern, Southern and Eastern Europe and Argentina, between January 2004 and December 2006 were enrolled in the TB-HIV study. A weighted HCI score (range 0–5), based on independent prognostic factors identified in multivariable Cox models and the final score, included performance of TB drug susceptibility testing (DST), an initial TB regimen containing a rifamycin, isoniazid and pyrazinamide, and start of combination antiretroviral treatment (cART). RESULTS: The mean HCI score was highest in Central/Northern Europe (3.2, 95%CI 3.1–3.3) and lowest in Eastern Europe (1.6, 95%CI 1.5–1.7). The cumulative probability of death 1 year after TB diagnosis decreased from 39% (95%CI 31–48) among patients with an HCI score of 0, to 9% (95%CI 6–13) among those with a score of ≥4. In an adjusted Cox model, a 1-unit increase in the HCI score was associated with 27% reduced mortality (relative hazard 0.73, 95%CI 0.64–0.84). CONCLUSIONS: Our results suggest that DST, standard anti-tuberculosis treatment and early cART may improve outcome for TB-HIV patients. The proposed HCI score provides a tool for future research and monitoring of the management of TB-HIV patients. The highest HCI score may serve as a benchmark to assess TB-HIV management, encouraging continuous health care improvement.
Published: 2013

8. Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients.

Author: Swiss HIV Cohort Study, Remy, B., Rickenbach, M., Schöni-Affolter, F., Vallet, Y., Francioli, MC., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Rudin, C., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Scherrer, A.U., von Wyl, V., Vernazza, P.L., Günthard, H.F., Swiss HIV Cohort Study, Remy, B., Rickenbach, M., Schöni-Affolter, F., Vallet, Y., Francioli, MC., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Rudin, C., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Scherrer, A.U., von Wyl, V., Vernazza, P.L., and Günthard, H.F.
Abstract: BACKGROUND: Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naïve patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential. METHODS: To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥ 1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs. RESULTS: We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥ 4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥ 1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0-1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5-1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome. CONCLUSIONS: The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.
Published: 2012

9. Tuberculosis in HIV-negative and HIV-infected patients in a low-incidence country: clinical characteristics and treatment outcomes.

Author: Swiss HIV Cohort, Molecular Epidemiology of Tuberculosis Study Groups, Fenner, L., Egger, M., Gagneux, S., Tanner, M., Furrer, H., Böttger, EC., Frei, R., Bodmer, T., Ninet, B., Schrenzel, J., Jaton, K., Telenti, A., Siegrist, H., Pfyffer, GE., Bruderer, T., Dolina, M., Dubuis, O., Battegay, M., Bernasconi, E., Hoffmann, M., Cavassini, M., Hirschel, B., Calmy, A., Fehr, J., Janssens, JP., Stalder, JM., Helbling, P., Altpeter, E., Rieder, HL., Barth, J., Böni, J., Bucher, HC., Burton-Jeangros, C., Cellerai, C., Elzi, L., Fellay, J., Flepp, M., Francioli, P., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Janssens, J.P., Böttger, E.C., Swiss HIV Cohort, Molecular Epidemiology of Tuberculosis Study Groups, Fenner, L., Egger, M., Gagneux, S., Tanner, M., Furrer, H., Böttger, EC., Frei, R., Bodmer, T., Ninet, B., Schrenzel, J., Jaton, K., Telenti, A., Siegrist, H., Pfyffer, GE., Bruderer, T., Dolina, M., Dubuis, O., Battegay, M., Bernasconi, E., Hoffmann, M., Cavassini, M., Hirschel, B., Calmy, A., Fehr, J., Janssens, JP., Stalder, JM., Helbling, P., Altpeter, E., Rieder, HL., Barth, J., Böni, J., Bucher, HC., Burton-Jeangros, C., Cellerai, C., Elzi, L., Fellay, J., Flepp, M., Francioli, P., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Janssens, J.P., and Böttger, E.C.
Abstract: BACKGROUND: In Switzerland and other developed countries, the number of tuberculosis (TB) cases has been decreasing for decades, but HIV-infected patients and migrants remain risk groups. The aim of this study was to compare characteristics of TB in HIV-negative and HIV-infected patients diagnosed in Switzerland, and between coinfected patients enrolled and not enrolled in the national Swiss HIV Cohort Study (SHCS). METHODS AND FINDINGS: All patients diagnosed with culture-confirmed TB in the SHCS and a random sample of culture-confirmed cases reported to the national TB registry 2000-2008 were included. Outcomes were assessed in HIV-infected patients and considered successful in case of cure or treatment completion. Ninety-three SHCS patients and 288 patients selected randomly from 4221 registered patients were analyzed. The registry sample included 10 (3.5%) coinfected patients not enrolled in the SHCS: the estimated number of HIV-infected patients not enrolled in the SHCS but reported to the registry 2000-2008 was 146 (95% CI 122-173). Coinfected patients were more likely to be from sub-Saharan Africa (51.5% versus 15.8%, P<0.0001) and to present disseminated disease (23.9% vs. 3.4%, P<0.0001) than HIV-negative patients. Coinfected patients not enrolled in the SHCS were asylum seekers or migrant workers, with lower CD4 cell counts at TB diagnosis (median CD4 count 79 cells/µL compared to 149 cells/µL among SHCS patients, P = 0.07). There were 6 patients (60.0%) with successful outcomes compared to 82 (88.2%) patients in the SHCS (P = 0.023). CONCLUSIONS: The clinical presentation of coinfected patients differed from HIV-negative TB patients. The number of HIV-infected patients diagnosed with TB outside the SHCS is similar to the number diagnosed within the cohort but outcomes are poorer in patients not followed up in the national cohort. Special efforts are required to address the needs of this vulnerable population.
Published: 2012

10. Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations

Author: von Wyl, V, Yerly, S, Böni, J, Shah, C, Cellerai, C, Klimkait, T, Battegay, M, Bernasconi, E, Cavassini, M, Furrer, H, Hirschel, B, Vernazza, P L, Ledergerber, B, Günthard, H F, von Wyl, V, Yerly, S, Böni, J, Shah, C, Cellerai, C, Klimkait, T, Battegay, M, Bernasconi, E, Cavassini, M, Furrer, H, Hirschel, B, Vernazza, P L, Ledergerber, B, and Günthard, H F
Abstract: Background. Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence. Methods. Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range). Results. Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (<11%). Confounder-adjusted Cox regression confirmed that first-line EFV plus AZT (reference) was associated with a higher median hazard for resistance emergence, compared with other treatments: EFV plus TDF (hazard ratio [HR], 0.57; range, 0.42-0.76), LPV plus AZT (HR, 0.63; range, 0.45-0.89), LPV plus TDF (HR, 0.55; range, 0.33-0.83), ATZ/r plus TDF (HR, 0.43; range, 0.17-0.83). Two-thirds of resistance events were associated with detectable HIV RNA level ≤500 copies/mL during treatment, and only one-third with virological failure (HIV RNA level, >500 copies/mL). Conclusions. The inclusion of TDF instead of AZT and ATZ/r w
Published: 2012

11. Assessing predicted HIV-1 replicative capacity in a clinical setting

Author: Kouyos, R D, von Wyl, V, Hinkley, T, Petropoulos, C J, Haddad, M, Whitcomb, J M, Böni, J, Yerly, S, Cellerai, C, Klimkait, T, Günthard, H F, Bonhoeffer, S, Kouyos, R D, von Wyl, V, Hinkley, T, Petropoulos, C J, Haddad, M, Whitcomb, J M, Böni, J, Yerly, S, Cellerai, C, Klimkait, T, Günthard, H F, and Bonhoeffer, S
Abstract: HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learning tool, which predicts RC values from partial pol sequences with genotypic and clinical data from the Swiss HIV Cohort Study. The machine-learning tool is based on a training set consisting of 65000 RC measurements paired with their corresponding partial pol sequences. We find that predicted RC values (pRCs) correlate significantly with the virus load measured in 2073 infected but drug naïve individuals. Furthermore, we find that, for 53 pairs of sequences, each pair sampled in the same infected individual, the pRC was significantly higher for the sequence sampled later in the infection and that the increase in pRC was also significantly correlated with the increase in plasma viral load and with the length of the time-interval between the sampling points. These findings indicate that selection within a patient favors the evolution of higher replicative capacities and that these in-vitro fitness measures are indicative of in-vivo HIV virus load.
Published: 2011

12. 1412 COMPARATIVE GENETIC ANALYSES POINT TO HCP5 AS SUSCEPTIBILITY LOCUS FOR HCV-ASSOCIATED HEPATOCELLULAR CARCINOMA

Author: Lange, C.M., primary, Bibert, S., additional, Dufour, J.-F., additional, Cellerai, C., additional, Cerny, A., additional, Heim, M.H., additional, Kaiser, L., additional, Malinverni, R., additional, Müllhaupt, B., additional, Negro, F., additional, Semela, D., additional, Moradpour, D., additional, Kutalik, Z., additional, and Bochud, P.-Y., additional
Published: 2013
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13. Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype

Author: Harari, A., Cellerai, C., Enders, F.B., Kostler, J., Codarri, L., Tapia, G., Boyman, O., Castro, E., Gaudieri, S., James, I., John, M., Wagner, R., Mallal, S., Pantaleo, G., Harari, A., Cellerai, C., Enders, F.B., Kostler, J., Codarri, L., Tapia, G., Boyman, O., Castro, E., Gaudieri, S., James, I., John, M., Wagner, R., Mallal, S., and Pantaleo, G.
Abstract: We studied CD8 T cell responses against HIV-1, cytomegalovirus, Epstein-Barr virus, and influenza in 128 subjects and demonstrate that polyfunctional CD8 T cell responses, also including IL-2 production and Ag-specific proliferation, are predominantly driven by virus epitopes restricted by HLA-B alleles. Interestingly, these protective CD8 T cells are equipped with low-avidity T cell receptors (TCRs) for the cognate virus epitope. Conversely, HLA-Arestricted epitopes are mostly associated with "only effector" IFN-γ-secreting, with cytotoxicity, and with the lack of IL-2 production and Ag-specific proliferation. These CD8 T cells are equipped with high-avidity TCR and express higher levels of the T cell exhaustion marker PD-1. Thus, the functional profile of the CD8 T cell response is strongly influenced by the extent to which there is stimulation of polyfunctional (predominantly restricted by HLA-B) versus only effector (restricted by HLA-A) T cell responses. These results provide the rationale for the observed protective role of HLA-B in HIV-1-infection and new insights into the relationship between TCR avidity, PD-1 expression, and the functional profile of CD8 T cells.
Published: 2007

14. Performance evaluation of a new fourth-generation HIV combination antigen–antibody assay

Author: Mühlbacher, A., primary, Schennach, H., additional, van Helden, J., additional, Hebell, T., additional, Pantaleo, G., additional, Bürgisser, P., additional, Cellerai, C., additional, Permpikul, P., additional, Rodriguez, M. I., additional, Eiras, A., additional, Alborino, F., additional, Cunningham, P., additional, Axelsson, M., additional, Andersson, S., additional, Wetlitzky, O., additional, Kaiser, C., additional, Möller, P., additional, and de Sousa, G., additional
Published: 2012
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15. Mycobacterium tuberculosis Transmission in a Country with Low Tuberculosis Incidence: Role of Immigration and HIV Infection

Author: Fenner, Lukas, primary, Gagneux, Sebastien, additional, Helbling, Peter, additional, Battegay, Manuel, additional, Rieder, Hans L., additional, Pfyffer, Gaby E., additional, Zwahlen, Marcel, additional, Furrer, Hansjakob, additional, Siegrist, Hans H., additional, Fehr, Jan, additional, Dolina, Marisa, additional, Calmy, Alexandra, additional, Stucki, David, additional, Jaton, Katia, additional, Janssens, Jean-Paul, additional, Stalder, Jesica Mazza, additional, Bodmer, Thomas, additional, Ninet, Beatrice, additional, Böttger, Erik C., additional, Egger, Matthias, additional, Barth, J., additional, Battegay, M., additional, Bernasconi, E., additional, Böni, J., additional, Bucher, H. C., additional, Burton-Jeangros, A. Calmy, additional, Cavassini, M., additional, Cellerai, C., additional, Egger, M., additional, Elzi, L., additional, Fehr, J., additional, Fellay, J., additional, Flepp, M., additional, Francioli, P., additional, Furrer, H., additional, Fux, C. A., additional, Gorgievski, M., additional, Günthard, H., additional, Haerry, D., additional, Hasse, B., additional, Hirschel, B., additional, Hirsch, H. H., additional, Hoffmann, M., additional, Hösli, I., additional, Kahlert, C., additional, Kaiser, L., additional, Kaiser, O., additional, Kind, C., additional, Klimkait, T., additional, Kovari, H., additional, Ledergerber, B., additional, Lugano, A. P., additional, Martinetti, G., additional, Martinez de Tejada, B., additional, Metzner, K., additional, Müller, N., additional, Nadal, D., additional, Pantaleo, G., additional, Rauch, A., additional, Regenass, S., additional, Rickenbach, M., additional, Rudin, C., additional, Schmid, P., additional, Schultze, D., additional, Schöni-Affolter, F., additional, Schüpbach, J., additional, Speck, R., additional, Taffé, P., additional, Tarr, P., additional, Telenti, A., additional, Trkola, A., additional, Vernazza, P., additional, Weber, R., additional, and Yerly, S., additional
Published: 2012
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16. P16-48. Immunologic and virologic characterization of an ART-treated HIV-1 patients cohort with long-term control of viremia

Author: Kinloch, S, primary, Cellerai, C, additional, Yerly, S, additional, Byrne, P, additional, Carroll, A, additional, Stauss, H, additional, Johnson, A, additional, Harari, A, additional, and Pantaleo, G, additional
Published: 2009
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17. P16-32. Antigen exposure regulates the balance between proliferating and cytotoxic subsets of virus-specific CD8 T-cells

Author: Cellerai, C, primary, Perreau, M, additional, Rozot, V, additional, Enders, F Bellutti, additional, Bart, P, additional, Pantaleo, G, additional, and Harari, A, additional
Published: 2009
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18. Role of retroviral restriction factors in the interferon- -mediated suppression of HIV-1 in vivo

Author: Pillai, S. K., Abdel-Mohsen, M., Guatelli, J., Skasko, M., Monto, A., Fujimoto, K., Yukl, S., Greene, W. C., Kovari, H., Rauch, A., Fellay, J., Battegay, M., Hirschel, B., Witteck, A., Bernasconi, E., Ledergerber, B., Gunthard, H. F., Wong, J. K., Barth, J., Boni, J., Bucher, H., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Flepp, M., Francioli, P., Furrer, H., Fux, C., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H., Hosli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Martinetti, G., Martinez De Tejada, B., Metzner, K., Muller, N., Nadal, D., Pantaleo, G., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schoni-Affolter, F., Schupbach, J., Speck, R., Taffe, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: virus diseases
Abstract: The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro.Wesought to characterize the as-yet- undefinedrelationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log 10copies/mL in HIV/HCV-coinfected patients.APOBEC3G/3F andBST-2mRNAexpression was significantly elevated during IFN-á/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

19. Identification of an Endoglin Variant Associated With HCV-Related Liver Fibrosis Progression by Next-Generation Sequencing

Author: Frédégonde About, Stéphanie Bibert, Emmanuelle Jouanguy, Bertrand Nalpas, Lazaro Lorenzo, Vimel Rattina, Mohammed Zarhrate, Sylvain Hanein, Mona Munteanu, Beat Müllhaupt, David Semela, Nasser Semmo, Jean-Laurent Casanova, Ioannis Theodorou, Philippe Sultanik, Thierry Poynard, Stanislas Pol, Pierre-Yves Bochud, Aurélie Cobat, Laurent Abel, The Swiss Hepatitis C Cohort Study Group, The French ANRS HC EP 26 Genoscan Study Group, Francesco Negro, Antoine Hadengue, Laurent Kaiser, Laura Rubbia-Brandt, Darius Moradpour, Cristina Cellerai, Martin Rickenbach, Andreas Cerny, Gladys Martinetti, Jean-François Dufour, Meri Gorgievski, Virginie Masserey Spicher, Markus Heim, Hans Hirsch, Beat Helbling, Stephan Regenass, Raffaele Malinverni, Guenter Dollenmaier, Gieri Cathomas, University of Zurich, Cobat, Aurélie, Negro, Francesco, Hadengue, Antoine, Kaiser, Laurent, Rubbia-Brandt, Laura, Swiss Hepatitis C Cohort Study Group, French ANRS HC EP 26 Genoscan Study Group, Negro, F., Hadengue, A., Kaiser, L., Rubbia-Brandt, L., Moradpour, D., Cellerai, C., Rickenbach, M., Cerny, A., Martinetti, G., Dufour, J.F., Gorgievski, M., Spicher, V.M., Heim, M., Hirsch, H., Helbling, B., Regenass, S., Malinverni, R., Dollenmaier, G., Cathomas, G., Bousquet, L., Ngo, Y., Lebray, P., Moussalli, J., Benhamou, Y., Thabut, D., Vallet-Pichard, A., Fontaine, H., Mallet, V., Sogni, P., Trabut, J.B., Bourlière, M., Delfraissy, J.F., Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Infectious Disease Service, Department of Internal Medicine, Université de Lausanne = University of Lausanne (UNIL), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Hôpital Universitaire de Réadaptation, de Rééducation et d'Addictologie du CHU de Nîmes [Grau-du-Roi] (CHU Nîmes), BioPredictive [Paris], University hospital of Zurich [Zurich], University of Bern, Bern University Hospital [Berne] (Inselspital), Laboratory of Human Genetics of Infectious Diseases (Necker Branch - INSERM U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Rockefeller University [New York], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie du système immunitaire (Inserm U1223), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), and Génétique Humaine des Maladies Infectieuses (Inserm U980)
Subjects: 0301 basic medicine, 2716 Genetics (clinical), lcsh:QH426-470, rare-variant association study, [SDV]Life Sciences [q-bio], 610 Medicine & health, ddc:616.07, Virus, 03 medical and health sciences, 0302 clinical medicine, 1311 Genetics, Fibrosis, TGF beta signaling pathway, Genetics, Medicine, HCV-related liver fibrosis, TGF-beta, endoglin, exome sequencing, Exome, Genetics (clinical), Exome sequencing, Genetic association, ddc:616, business.industry, Odds ratio, Brief Research Report, Endoglin, medicine.disease, 3. Good health, lcsh:Genetics, 030104 developmental biology, 10219 Clinic for Gastroenterology and Hepatology, 030220 oncology & carcinogenesis, 1313 Molecular Medicine, Immunology, Molecular Medicine, business
Abstract: International audience; Despite the astonishing progress in treating chronic hepatitis C virus (HCV) infection with direct-acting antiviral agents, liver fibrosis remains a major health concern in HCV infected patients, in particular due to the treatment cost and insufficient HCV screening in many countries. Only a fraction of patients with chronic HCV infection develop liver fibrosis. While there is evidence that host genetic factors are involved in the development of liver fibrosis, the common variants identified so far, in particular by genome-wide association studies, were found to have limited effects. Here, we conducted an exome association study in 88 highly selected HCV-infected patients with and without fibrosis. A strategy focusing on TGF-β pathway genes revealed an enrichment in rare variants of the endoglin gene (ENG) in fibrosis patients. Replication studies in additional cohorts (617 patients) identified one specific ENG variant, Thr5Met, with an overall odds ratio for fibrosis development in carriers of 3.04 (1.39-6.69). Our results suggest that endoglin, a key player in TGF-β signaling, is involved in HCV-related liver fibrogenesis.
Published: 2019
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20. HBV genotypes and response to tenofovir disoproxil fumarate in HIV/HBV-coinfected persons

Author: Florian, Bihl, Gladys, Martinetti, Gilles, Wandeler, Rainer, Weber, Bruno, Ledergeber, Alexandra, Calmy, Manuel, Battegay, Matthias, Cavassini, Pietro, Vernazza, Anna-Paola, Caminada, Martin, Rickenbach, Enos, Bernasconi, S, Yerly, University of Zurich, Bihl, Florian, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Male, HIV Infections, medicine.disease_cause, 10234 Clinic for Infectious Diseases, Genotype, Young adult, 610 Medicine & health, Coinfection, Gastroenterology, Lamivudine, virus diseases, General Medicine, Hepatitis B, Middle Aged, Viral Load, Female, Adult, Aged, Antiviral Agents/therapeutic use, Coinfection/drug therapy, Coinfection/virology, Drug Resistance, Viral/genetics, HIV Infections/complications, HIV Infections/drug therapy, Hepatitis B/complications, Hepatitis B/drug therapy, Hepatitis B virus/genetics, Humans, Lamivudine/therapeutic use, Retrospective Studies, Switzerland, Tenofovir/therapeutic use, Viral Load/drug effects, Young Adult, Viral load, 360 Social problems & social services, medicine.drug, Research Article, medicine.medical_specialty, Hepatitis B virus, Antiviral Agents, Internal medicine, Drug Resistance, Viral, medicine, 2715 Gastroenterology, Tenofovir, business.industry, Hepatology, medicine.disease, Virology, digestive system diseases, Immunology, 10033 Clinic for Immunology, business
Abstract: BACKGROUND: Hepatitis B virus (HBV) genotypes can influence treatment outcome in HBV-monoinfected and human immunodeficiency virus (HIV)/HBV-coinfected patients. Tenofovir disoproxil fumarate (TDF) plays a pivotal role in antiretroviral therapy (ART) of HIV/HBV-coinfected patients. The influence of HBV genotypes on the response to antiviral drugs, particularly TDF, is poorly understood. METHODS: HIV/HBV-co-infected participants with detectable HBV DNA prior to TDF therapy were selected from the Swiss HIV Cohort Study. HBV genotypes were identified and resistance testing was performed prior to antiviral therapy, and in patients with delayed treatment response (>6 months). The efficacy of TDF to suppress HBV (HBV DNA
Published: 2015
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21. Higher memory responses in HIV-infected and kidney transplanted patients than in healthy subjects following priming with the pandemic vaccine

Author: Cécile Delhumeau, Christian van Delden, Christophe Combescure, Claire-Anne Siegrist, Olivier F. Clerc, Paola M. Soccal, Karine Hadaya, Matthias Cavassini, Sara Meier, Laurent Kaiser, Alexandra Calmy, Michael Bel, Bernard Hirschel, Sabine Yerly, H1N1 Study Group, Swiss HIV Cohort Study (SHCS), Siegrist, CA., Posfay-Barbe, K., Meier, S., Bel, M., Grillet, S., Sealy, G., Demeules, J., Charvat, S., Verdon, M., Combescure, C., Hirschel, B., Calmy, A., Delhumeau-Cartier, C., Gabay, C., Guerne, PA., Seebach, J., Ribi, C., Villard, J., Dietrich, PY., George, AC., Favet, L., van Delden, C., Morard, I., Mentha, G., Giostra, E., Hadaya, K., Martin, PY., Soccal, P., Berney, T., Noble, S., Mohty, B., Nagy, M., Chalandon, Y., Roosnek, E., Passweg, J., Kaiser, L., Yerly, S., Thomas, Y., Wunderli, W., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Posfay Barbe, Klara, and Grillet, Stéphane
Subjects: Male, lcsh:Medicine, Adult, Aged, Antibodies, Viral/blood, Antibodies, Viral/immunology, Female, HIV Infections/blood, HIV Infections/immunology, Humans, Immunocompromised Host, Immunologic Memory/drug effects, Influenza Vaccines/administration & dosage, Influenza, Human/blood, Influenza, Human/immunology, Kidney Transplantation/immunology, Middle Aged, Pandemics, HIV Infections/blood/immunology, HIV Infections, ddc:616.07, Antibodies, Viral, 0302 clinical medicine, Pandemic, 030212 general & internal medicine, lcsh:Science, Prospective cohort study, Kidney transplantation, ddc:616, 0303 health sciences, Multidisciplinary, ddc:617, biology, Vaccination, Antibody titer, HIV diagnosis and management, 3. Good health, Titer, Influenza, Human/blood/immunology/prevention & control, Influenza Vaccines, Medicine, Infectious diseases, HIV clinical manifestations, Antibody, Research Article, Retrovirology and HIV immunopathogenesis, Viral diseases, 03 medical and health sciences, Immune system, Influenza, Human, medicine, Antibodies, Viral/blood/immunology, 030306 microbiology, business.industry, lcsh:R, Immunity, HIV, medicine.disease, Kidney Transplantation, Institutional repository, Immunology, biology.protein, lcsh:Q, Clinical Immunology, business, Immunologic Memory
Abstract: BACKGROUND: Memory responses require immune competence. We assessed the influence of priming with AS03-adjuvanted pandemic vaccine (Pandemrix®) on memory responses of HIV patients, kidney recipients (SOT) and healthy controls (HC). METHOD: Participants (HIV: 197, SOT: 53; HC: 156) were enrolled in a prospective study and 390/406 (96%) completed it. All had been primed in 2009/2010 with 1 (HC) or 2 (patients) doses of Pandemrix®, and were boosted with the 2010/2011 seasonal influenza vaccine. Geometric mean titres and seroprotection rates were measured 12 months after priming and 4 weeks after boosting. Primary and memory responses were directly compared in 191 participants (HCW: 69, HIV: 71, SOT: 51) followed during 2 consecutive seasons. RESULTS: Most participants (HC: 77.8%, HIV: 77.6%, SOT: 66%) remained seroprotected at 12 months post-priming. Persisting A/09/H1N1 titers were high in HIV (100.2) and HC (120.1), but lower in SOT (61.4) patients. Memory responses reached higher titers in HIV (507.8) than in HC (253.5) and SOT (136.9) patients. Increasing age and lack of HAART reduced persisting and memory responses, mainly influenced by residual antibody titers. Comparing 2009/2010 and 2010/2011 titers in 191 participants followed for 2 seasons indicated lower post-2010/2011 titers in HC (240.2 vs 313.9), but higher titers in HIV (435.7 vs 338.0) and SOT (136 vs 90.3) patients. CONCLUSIONS: Priming with 2 doses of Pandemrix® elicited persistent antibody responses and even stronger memory responses to non-adjuvanted seasonal vaccine in HIV patients than 1 dose in healthy subjects. Adjuvanted influenza vaccines may improve memory responses of immunocompromised patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01022905.
Published: 2012

22. Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients

Author: Alexandra U Scherrer, Bruno Ledergerber, Viktor von Wyl, Jürg Böni, Sabine Yerly, Thomas Klimkait, Cristina Cellerai, Hansjakob Furrer, Alexandra Calmy, Matthias Cavassini, Luigia Elzi, Pietro L Vernazza, Enos Bernasconi, Huldrych F Günthard, Swiss HIV Cohort Study, University of Zurich, Swiss HIV Cohort Study, Remy, B., Rickenbach, M., Schöni-Affolter, F., Vallet, Y., Francioli, MC., Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Rudin, C., Schmid, P., Schultze, D., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Male, 10028 Institute of Medical Virology, lcsh:Medicine, HIV Infections, medicine.disease_cause, Gastroenterology, Nucleoside Reverse Transcriptase Inhibitor, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, HIV Protease, HIV Protease Inhibitor, 030212 general & internal medicine, lcsh:Science, ddc:616, 0303 health sciences, Mutation, Multidisciplinary, Hazard ratio, HIV diagnosis and management, Viral Load, 3. Good health, HIV epidemiology, Cohort, RNA, Viral, Medicine, Infectious diseases, HIV clinical manifestations, Female, Viral load, Research Article, medicine.medical_specialty, Retrovirology and HIV immunopathogenesis, Sexually Transmitted Diseases, 610 Medicine & health, Viral diseases, 1100 General Agricultural and Biological Sciences, Biology, 03 medical and health sciences, CD4 Lymphocyte Count, Drug Resistance, Viral/genetics, HIV Infections/drug therapy, HIV Infections/virology, HIV Protease/genetics, HIV Protease Inhibitors/pharmacology, HIV Protease Inhibitors/therapeutic use, Humans, RNA, Viral/blood, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Drug Resistance, Viral, medicine, Genetics, HIV Protease Inhibitors/pharmacology/therapeutic use, Protease inhibitor (pharmacology), HIV Infections/drug therapy/virology, 030304 developmental biology, Evolutionary Biology, 1000 Multidisciplinary, Population Biology, Proportional hazards model, lcsh:R, Computational Biology, HIV, HIV Protease Inhibitors, Immunology, Genetic Polymorphism, 570 Life sciences, biology, lcsh:Q, Population Genetics
Abstract: Background Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naive patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential. Methods To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs. Results We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0–1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5–1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome. Conclusions The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.
Published: 2012
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23. Determinants of sustained viral suppression in HIV-infected patients with self-reported poor adherence to antiretroviral therapy

Author: Bernard Hirschel, Chantal Csajka, Enos Bernasconi, Margalida Rotger, Laurent A. Decosterd, Huldrych F. Günthard, Amalio Telenti, Martin Rickenbach, Catia Marzolini, Dunja Nicca, Heiner C. Bucher, Tracy R. Glass, Gilles Wandeler, Manuel Battegay, University of Zurich, Marzolini, Catia, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, C., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, Ch., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., and Yerly, S.
Subjects: Male, Viral Diseases, Time Factors, Adult, Anti-HIV Agents/pharmacology, Anti-HIV Agents/therapeutic use, HIV Infections/drug therapy, HIV Infections/genetics, HIV-1/drug effects, Humans, Logistic Models, Longitudinal Studies, Middle Aged, Patient Compliance/statistics & numerical data, Self Report, HIV Infections, 10234 Clinic for Infectious Diseases, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, 0303 health sciences, education.field_of_study, Multidisciplinary, biology, Lopinavir, Multidrug Resistance-Associated Protein 2, 3. Good health, Infectious Diseases, Medicine, medicine.drug, Research Article, medicine.medical_specialty, Drugs and Devices, Efavirenz, Anti-HIV Agents, Science, Population, 610 Medicine & health, Single-nucleotide polymorphism, 1100 General Agricultural and Biological Sciences, Microbiology, 03 medical and health sciences, Pharmacotherapy, 1300 General Biochemistry, Genetics and Molecular Biology, Internal medicine, Virology, medicine, education, Biology, Clinical Genetics, 1000 Multidisciplinary, 030306 microbiology, business.industry, Odds ratio, Confidence interval, chemistry, Immunology, biology.protein, HIV-1, Patient Compliance, SLCO1B1, business
Abstract: BackgroundGood adherence to antiretroviral therapy (ART) is critical for successful HIV treatment. However, some patients remain virologically suppressed despite suboptimal adherence. We hypothesized that this could result from host genetic factors influencing drug levels.MethodsEligible individuals were Caucasians treated with efavirenz (EFV) and/or boosted lopinavir (LPV/r) with self-reported poor adherence, defined as missing doses of ART at least weekly for more than 6 months. Participants were genotyped for single nucleotide polymorphisms (SNPs) in candidate genes previously reported to decrease EFV (rs3745274, rs35303484, rs35979566 in CYP2B6) and LPV/r clearance (rs4149056 in SLCO1B1, rs6945984 in CYP3A, rs717620 in ABCC2). Viral suppression was defined as having HIV-1 RNA ResultsFrom January 2003 until May 2009, 37 individuals on EFV (28 suppressed and 9 not suppressed) and 69 on LPV/r (38 suppressed and 31 not suppressed) were eligible. The poor adherence period was a median of 32 weeks with 18.9% of EFV and 20.3% of LPV/r patients reporting missed doses on a daily basis. The tested SNPs were not determinant for viral suppression. Reporting missing >1 dose/week was associated with a lower probability of viral suppression compared to missing 1 dose/week (EFV: odds ratio (OR) 0.11, 95% confidence interval (CI): 0.01-0.99; LPV/r: OR 0.29, 95% CI: 0.09-0.94). In both groups, the probability of remaining suppressed increased with the duration of continuous suppression prior to the poor adherence period (EFV: OR 3.40, 95% CI: 0.62-18.75; LPV/r: OR 5.65, 95% CI: 1.82-17.56).ConclusionsThe investigated genetic variants did not play a significant role in the sustained viral suppression of individuals with suboptimal adherence. Risk of failure decreased with longer duration of viral suppression in this population.
Published: 2012
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24. Genome-Wide Association Study Identifies Variants Associated With Progression of Liver Fibrosis From HCV Infection

Author: Thierry Poynard, Beat Müllhaupt, Jean-Laurent Casanova, Stanislas Pol, Ioannis Theodorou, Zoltán Kutalik, Andrew H. Talal, Mona Munteanu, Raffaele Malinverni, Philippe Halfon, Pierre-Yves Bochud, Darius Moradpour, Markus H. Heim, Francesco Negro, Ira M. Jacobson, Charles M. Rice, Stéphanie Bibert, Bertrand Nalpas, Christian Bréchot, Jacob George, Laurence Bousquet, Etienne Patin, Laurent Abel, Hans H. Hirsch, Gladys Martinetti, Vijayaprakash Suppiah, Jean-François Dufour, Graeme J. Stewart, Andreas Cerny, Anne Boland, Julien Guergnon, David Semela, David R. Booth, Marc Bourlière, Emmanuelle Jouanguy, Laurent Argiro, Human genetics of infectious diseases: Complex predisposition (Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Université Pierre et Marie Curie - Paris 6 - UFR de Médecine Pierre et Marie Curie (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC), Infectious Disease Service, Department of Internal Medicine, Service d'hépatologie médicale [CHU Cochin], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biopredictive, Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et immunologie des maladies parasitaires (GIMP), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Médecine générale, Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Européen [Fondation Ambroise Paré - Marseille], Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University hospital of Zurich [Zurich], University of Bern, Division of Gastroenterology and Hepatology, Institut für Medizinischediagnostik, Mikrobiologie, University of Bassel, School of Life Sciences, University of Technology Sydney (UTS), Pathogénèse et traitement de l'hépatite fulminante et du cancer du foie, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Weill Medical College of Cornell University [New York], Service d'hépatologie et de gastroentérologie [Hôpital Saint-Joseph - Marseille], Aix Marseille Université (AMU)-Hôpital Saint-Joseph [Marseille], Immunité et Infection, IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Lausanne (UNIL), University Hospital and University of Lausanne, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR113-Sorbonne Université (SU), Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Swiss Hepatitis C Cohort Study Group, International Hepatitis C Genetics Consortium, French ANRS HC EP 26 Genoscan Study Group, Negro, F., Hadengue, A., Kaiser, L., Rubbia-Brandt, L., Moradpour, D., Cellerai, C., Rickenbach, M., Cerny, A., Martinetti, G., Dufour, J.F., Gorgievski, M., Masserey Spicher, V., Heim, M., Hirsch, H., Müllhaupt, B., Helbling, B., Regenass, S., Malinverni, R., Semela, D., Dollenmaier, G., Cathomas, G., Suppiah, V., Berg, T., Weltman, M., Abate, M.L., Spengler, U., Bassendine, M., Dore, G.J., Irving, W.L., Powell, E., Riordan, S., Ahlenstiehl, G., Stewart, G., Booth, D.R., George, J., Nalpas, B., Abel, L., Monteanu, M., Bousquet, L., Ngo, Y., Lebray, P., Moussalli, J., Benhamou, Y., Thabut, D., Vallet-Pichard, A., Fontaine, H., Mallet, V., Sogni, P., Trabut, J.B., Bourlière, M., Theodorou, I., Delfraissy, J.F., Poynard, T., Pol, S., Suppiah, Vijayaprakash, Patin, Etienne, Kutalik, Zoltan, Geurgnon, Julien, Bibert, Stephanie, and Laurent, Abel
Subjects: Liver Cirrhosis, Male, Hepatitis C, Chronic/complications/virology, Genome-wide association study, Apoptosis, genetic analysis, Hepacivirus, ddc:616.07, Liver disease, 0302 clinical medicine, Fibrosis, Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Apoptosis/genetics, risk factors, ddc:616, 0303 health sciences, Liver Disease, Gastroenterology, virus diseases, Genetic Analysis, Hepatitis C, 3. Good health, Phenotype, Cirrhosis, Disease Progression, 030211 gastroenterology & hepatology, Female, liver disease, Viral hepatitis, Adult, Genotype, Eye Proteins/genetics, Genome-Wide Association Study, Hepatitis C, Chronic/complications, Hepatitis C, Chronic/virology, Humans, Lipase/genetics, Liver Cirrhosis/genetics, Liver Cirrhosis/virology, Logistic Models, Membrane Proteins/genetics, Polymorphism, Single Nucleotide, Proportional Hazards Models, Proto-Oncogene Proteins/genetics, Receptor Protein-Tyrosine Kinases/genetics, Ubiquitin-Protein Ligases/genetics, Young Adult, Ubiquitin-Protein Ligases, Single-nucleotide polymorphism, C-Mer Tyrosine Kinase, Biology, Article, 03 medical and health sciences, Proto-Oncogene Proteins, medicine, SNP, Eye Proteins, 030304 developmental biology, Hepatology, c-Mer Tyrosine Kinase, cirrhosis, Membrane Proteins, Receptor Protein-Tyrosine Kinases, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Lipase, Hepatitis C, Chronic, medicine.disease, Liver Cirrhosis/genetics/virology, digestive system diseases, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Immunology
Abstract: BACKGROUND AIMS: Polymorphisms in IL28B were shown to affect clearance of hepatitis C virus (HCV) infection in genome wide association (GWA) studies. Only a fraction of patients with chronic HCV infection develop liver fibrosis a process that might also be affected by genetic factors. We performed a 2 stage GWA study of liver fibrosis progression related to HCV infection. METHODS: We studied well characterized HCV infected patients of European descent who underwent liver biopsies before treatment. We defined various liver fibrosis phenotypes on the basis of METAVIR scores with and without taking the duration of HCV infection into account. Our GWA analyses were conducted on a filtered primary cohort of 1161 patients using 780650 single nucleotide polymorphisms (SNPs). We genotyped 96 SNPs with P values
Published: 2012
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25. Incidence of HIV-1 drug resistance among antiretroviral treatment-naive individuals starting modern therapy combinations

Author: von Wyl, Viktor, Yerly, Sabine, Böni, Jürg, Shah, Cyril, Cellerai, Cristina, Klimkait, Thomas, Battegay, Manuel, Bernasconi, Enos, Cavassini, Matthias, Furrer, Hansjakob, Hirschel, Bernard, Vernazza, Pietro L, Ledergerber, Bruno, Günthard, Huldrych F, Swiss HIV Cohort, Study, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Bürgisser, P., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Müller, N., Nadal, D., Pantaleo, C., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Telenti, A., Trkola, A., Vernazza, P., von Wyl, V., Weber, R., Yerly, S., University of Zurich, and von Wyl, V
Subjects: Oncology, 10028 Institute of Medical Virology, Male, Human immunodeficiency virus (HIV), HIV Infections, Drug resistance, medicine.disease_cause, 2726 Microbiology (medical), 10234 Clinic for Infectious Diseases, chemistry.chemical_compound, 0302 clinical medicine, 030212 general & internal medicine, ddc:616, 0303 health sciences, Incidence, Lamivudine, virus diseases, Lopinavir, Middle Aged, Viral Load, 3. Good health, HIV-1/classification/drug effects/genetics/isolation & purification, Infectious Diseases, Treatment Outcome, Female, medicine.drug, Microbiology (medical), Adult, medicine.medical_specialty, Efavirenz, Genotype, Anti-HIV Agents, 610 Medicine & health, Emtricitabine, 03 medical and health sciences, Zidovudine, Anti-HIV Agents/administration & dosage, Anti-HIV Agents/pharmacology, Drug Resistance, Viral, HIV Infections/drug therapy, HIV Infections/virology, HIV-1/classification, HIV-1/drug effects, Humans, Internal medicine, medicine, Antiretroviral treatment, HIV Infections/drug therapy/virology, 030306 microbiology, business.industry, Anti-HIV Agents/administration & dosage/pharmacology, 2725 Infectious Diseases, chemistry, Immunology, HIV-1, 570 Life sciences, biology, business
Abstract: BACKGROUND: Estimates of drug resistance incidence to modern first-line combination antiretroviral therapies against human immunodeficiency virus (HIV) type 1 are complicated by limited availability of genotypic drug resistance tests (GRTs) and uncertain timing of resistance emergence. METHODS: Five first-line combinations were studied (all paired with lamivudine or emtricitabine): efavirenz (EFV) plus zidovudine (AZT) (n = 524); EFV plus tenofovir (TDF) (n = 615); lopinavir (LPV) plus AZT (n = 573); LPV plus TDF (n = 301); and ritonavir-boosted atazanavir (ATZ/r) plus TDF (n = 250). Virological treatment outcomes were classified into 3 risk strata for emergence of resistance, based on whether undetectable HIV RNA levels were maintained during therapy and, if not, whether viral loads were >500 copies/mL during treatment. Probabilities for presence of resistance mutations were estimated from GRTs (n = 2876) according to risk stratum and therapy received at time of testing. On the basis of these data, events of resistance emergence were imputed for each individual and were assessed using survival analysis. Imputation was repeated 100 times, and results were summarized by median values (2.5th-97.5th percentile range). RESULTS: Six years after treatment initiation, EFV plus AZT showed the highest cumulative resistance incidence (16%) of all regimens (500 copies/mL). CONCLUSIONS: The inclusion of TDF instead of AZT and ATZ/r was correlated with lower rates of resistance emergence, most likely because of improved tolerability and pharmacokinetics resulting from a once-daily dosage.
Published: 2012
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26. Genetic Diversity of EBV-Encoded LMP1 in the Swiss HIV Cohort Study and Implication for NF-Κb Activation

Author: Zuercher, Emilie, Butticaz, Christophe, Wyniger, Josiane, Martinez, Raquel, Battegay, Manuel, Boffi El Amari, Emmanuelle, Dang, Thanh, Egger, Jean-François, Fehr, Jan, Mueller-Garamvögyi, Esther, Parini, Andrea, Schaefer, Stephan C, Schoeni-Affolter, Franziska, Thurnheer, Christine, Tinguely, Marianne, Telenti, Amalio, Rothenberger, Sylvia, Swiss HIV Cohort Study, Swiss HIV Cohort Study, Barth, J., Battegay, M., Bernasconi, E., Böni, J., Bucher, HC., Burton-Jeangros, C., Calmy, A., Cavassini, M., Cellerai, C., Egger, M., Elzi, L., Fehr, J., Fellay, J., Flepp, M., Francioli, P., Furrer, H., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hirschel, B., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Rothenberger, Sylvia
Subjects: Herpesvirus 4, Human, DNA Mutational Analysis, lcsh:Medicine, HIV Infections, Polymerase Chain Reaction, Hematologic Cancers and Related Disorders, 10234 Clinic for Infectious Diseases, 0302 clinical medicine, hemic and lymphatic diseases, Lymphocytes, lcsh:Science, Phylogeny, Genetics, 0303 health sciences, Multidisciplinary, Cancer Risk Factors, NF-kappa B, Transfection, Phenotype, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Medicine, Lymphomas, Research Article, Cell Survival, 610 Medicine & health, 1100 General Agricultural and Biological Sciences, Biology, Models, Biological, Microbiology, Virus, Viral Matrix Proteins, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, Virology, 10049 Institute of Pathology and Molecular Pathology, otorhinolaryngologic diseases, medicine, Humans, Transcription factor, 030304 developmental biology, 1000 Multidisciplinary, Polymorphism, Genetic, Activator (genetics), lcsh:R, HEK 293 cells, Genetic Variation, Cancers and Neoplasms, Cell Transformation, Viral, medicine.disease, Lymphoma, stomatognathic diseases, Nasopharyngeal carcinoma, Mutation, lcsh:Q, Cell Transformation, Viral/genetics, HIV Infections/virology, Herpesvirus 4, Human/genetics, Lymphocytes/virology, NF-kappa B/metabolism, Viral Matrix Proteins/metabolism
Abstract: Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1.
Published: 2012
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27. Tuberculosis in HIV-Negative and HIV-Infected Patients in a Low-Incidence Country: Clinical Characteristics and Treatment Outcomes

Author: Thomas Bodmer, Jacques Schrenzel, Sebastien Gagneux, Jean-Paul Janssens, Matthias Hoffmann, Enos Bernasconi, Erik C. Böttger, Lukas Fenner, Matthias Cavassini, Jan Fehr, Peter Helbling, Matthias Egger, Swiss HIV Cohort, Molecular Epidemiology of Tuberculosis Study Groups, Fenner, L., Egger, M., Gagneux, S., Tanner, M., Furrer, H., Böttger, EC., Frei, R., Bodmer, T., Ninet, B., Schrenzel, J., Jaton, K., Telenti, A., Siegrist, H., Pfyffer, GE., Bruderer, T., Dolina, M., Dubuis, O., Battegay, M., Bernasconi, E., Hoffmann, M., Cavassini, M., Hirschel, B., Calmy, A., Fehr, J., Janssens, JP., Stalder, JM., Helbling, P., Altpeter, E., Rieder, HL., Barth, J., Böni, J., Bucher, HC., Burton-Jeangros, C., Cellerai, C., Elzi, L., Fellay, J., Flepp, M., Francioli, P., Fux, CA., Gorgievski, M., Günthard, H., Haerry, D., Hasse, B., Hirsch, HH., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kind, C., Klimkait, T., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Metzner, K., Müller, N., Nadal, D., Pantaleo, G., Rauch, A., Regenass, S., Rickenbach, M., Rudin, C., Schmid, P., Schultze, D., Schöni-Affolter, F., Schüpbach, J., Speck, R., Taffé, P., Tarr, P., Trkola, A., Vernazza, P., Weber, R., Yerly, S., University of Zurich, and Fenner, Lukas
Subjects: Bacterial Diseases, CD4-Positive T-Lymphocytes, Male, Pediatrics, Viral Diseases, Epidemiology, lcsh:Medicine, HIV Infections, Comorbidity, 10234 Clinic for Infectious Diseases, Cohort Studies, 0302 clinical medicine, Adult, CD4-Positive T-Lymphocytes/cytology, Female, HIV Infections/complications, HIV Infections/epidemiology, HIV Seropositivity, Humans, Incidence, Middle Aged, Prospective Studies, Risk, Switzerland, Transients and Migrants, Treatment Outcome, Tuberculosis/complications, Tuberculosis/epidemiology, 030212 general & internal medicine, Prospective cohort study, lcsh:Science, ddc:616, 0303 health sciences, Multidisciplinary, 10179 Institute of Medical Microbiology, Incidence (epidemiology), 1. No poverty, virus diseases, 3. Good health, Infectious Diseases, Cohort, Medicine, Developed country, Cohort study, Research Article, medicine.medical_specialty, Tuberculosis, 610 Medicine & health, 1100 General Agricultural and Biological Sciences, Microbiology, 03 medical and health sciences, 1300 General Biochemistry, Genetics and Molecular Biology, Virology, medicine, Biology, HIV Infections/complications/epidemiology/virology, 1000 Multidisciplinary, 030306 microbiology, business.industry, lcsh:R, Extensively drug-resistant tuberculosis, Tropical Diseases (Non-Neglected), HIV, medicine.disease, Tuberculosis/complications/epidemiology/virology, 570 Life sciences, biology, lcsh:Q, business
Abstract: BACKGROUND: In Switzerland and other developed countries, the number of tuberculosis (TB) cases has been decreasing for decades, but HIV-infected patients and migrants remain risk groups. The aim of this study was to compare characteristics of TB in HIV-negative and HIV-infected patients diagnosed in Switzerland, and between coinfected patients enrolled and not enrolled in the national Swiss HIV Cohort Study (SHCS). METHODS AND FINDINGS: All patients diagnosed with culture-confirmed TB in the SHCS and a random sample of culture-confirmed cases reported to the national TB registry 2000-2008 were included. Outcomes were assessed in HIV-infected patients and considered successful in case of cure or treatment completion. Ninety-three SHCS patients and 288 patients selected randomly from 4221 registered patients were analyzed. The registry sample included 10 (3.5%) coinfected patients not enrolled in the SHCS: the estimated number of HIV-infected patients not enrolled in the SHCS but reported to the registry 2000-2008 was 146 (95% CI 122-173). Coinfected patients were more likely to be from sub-Saharan Africa (51.5% versus 15.8%, P
Published: 2012
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28. Prevalence and effect of pre-treatment drug resistance on the virological response to antiretroviral treatment initiated in HIV-infected children - a EuroCoord-CHAIN-EPPICC joint project.

Author: Ngo-Giang-Huong N, Wittkop L, Judd A, Reiss P, Goetghebuer T, Duiculescu D, Noguera-Julian A, Marczynska M, Giacquinto C, Ene L, Ramos JT, Cellerai C, Klimkait T, Brichard B, Valerius N, Sabin C, Teira R, Obel N, Stephan C, de Wit S, Thorne C, Gibb D, Schwimmer C, Campbell MA, Pillay D, and Lallemant M
Subjects: Adolescent, CD4 Lymphocyte Count, Child, Child, Preschool, Drug Resistance, Viral genetics, Drug Therapy, Combination, Female, HIV Infections mortality, HIV Infections virology, HIV-1 drug effects, Humans, Infant, Kaplan-Meier Estimate, Male, Mutation, Reverse Transcriptase Inhibitors therapeutic use, Viral Load drug effects, Anti-HIV Agents therapeutic use, Drug Resistance, Viral drug effects, HIV Infections drug therapy
Abstract: Background: Few studies have evaluated the impact of pre-treatment drug resistance (PDR) on response to combination antiretroviral treatment (cART) in children. The objective of this joint EuroCoord-CHAIN-EPPICC/PENTA project was to assess the prevalence of PDR mutations and their association with virological outcome in the first year of cART in children., Methods: HIV-infected children <18 years initiating cART between 1998 and 2008 were included if having at least one genotypic resistance test prior to cART initiation. We used the World Health Organization 2009 resistance mutation list and Stanford algorithm to infer resistance to prescribed drugs. Time to virological failure (VF) was defined as the first of two consecutive HIV-RNA > 500 copies/mL after 6 months cART and was assessed by Cox proportional hazards models. All models were adjusted for baseline demographic, clinical, immunology and virology characteristics and calendar period of cART start and initial cART regimen., Results: Of 476 children, 88 % were vertically infected. At cART initiation, median (interquartile range) age was 6.6 years (2.1-10.1), CD4 cell count 297 cells/mm 3 (98-639), and HIV-RNA 5.2 log 10 copies/mL (4.7-5.7). Of 37 children (7.8 %, 95 % confidence interval (CI), 5.5-10.6) harboring a virus with ≥1 PDR mutations, 30 children had a virus resistant to ≥1 of the prescribed drugs. Overall, the cumulative Kaplan-Meier estimate for virological failure was 19.8 % (95 %CI, 16.4-23.9). Cumulative risk for VF tended to be higher among children harboring a virus with PDR and resistant to ≥1 drug prescribed than among those receiving fully active cART: 32.1 % (17.2-54.8) versus 19.4 % (15.9-23.6) (P = 0.095). In multivariable analysis, age was associated with a higher risk of VF with a 12 % reduced risk per additional year (HR 0.88; 95 %CI, 0.82-0.95; P < 0.001)., Conclusions: PDR was not significantly associated with a higher risk of VF in children in the first year of cART. The risk of VF decreased by 12 % per additional year at treatment initiation which may be due to fading of PDR mutations over time. Lack of appropriate formulations, in particular for the younger age group, may be an important determinant of virological failure.
Published: 2016
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29. Aviremia 10 Years Postdiscontinuation of Antiretroviral Therapy Initiated During Primary Human Immunodeficiency Virus-1 Infection and Association With Gag-Specific T-Cell Responses.

Author: Kinloch-de Loes S, Dorrell L, Yang H, Hardy GA, Yerly S, Cellerai C, Vandekerckhove L, De Spielgelaere W, Malatinkova E, Wee Lee Koh W, and Johnson MA
Abstract: Combination antiretroviral therapy during primary human immunodeficiency virus-1 infection may enable long-term drug-free virological control in rare individuals. We describe a female who maintained aviremia and a normal CD4(+)/CD8(+) T cell ratio for 10 years after stopping therapy, despite a persistent viral reservoir. Cellular immune responses may have contributed to this outcome.
Published: 2015
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30. Comparative genetic analyses point to HCP5 as susceptibility locus for HCV-associated hepatocellular carcinoma.

Author: Lange CM, Bibert S, Dufour JF, Cellerai C, Cerny A, Heim MH, Kaiser L, Malinverni R, Müllhaupt B, Negro F, Semela D, Moradpour D, Kutalik Z, and Bochud PY
Subjects: Adult, Aged, Carcinoma, Hepatocellular immunology, Cohort Studies, Female, Genetic Predisposition to Disease, Hepatitis C, Chronic genetics, Hepatitis C, Chronic immunology, Histocompatibility Antigens Class I genetics, Humans, Liver Neoplasms immunology, Male, Middle Aged, Polymorphism, Single Nucleotide, RNA, Long Noncoding, RNA, Untranslated, Switzerland, White People genetics, Carcinoma, Hepatocellular etiology, Carcinoma, Hepatocellular genetics, Hepatitis C, Chronic complications, Liver Neoplasms etiology, Liver Neoplasms genetics, Major Histocompatibility Complex genetics
Abstract: Background & Aims: Recently, genetic variations in MICA (lead single nucleotide polymorphism [SNP] rs2596542) were identified by a genome-wide association study (GWAS) to be associated with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in Japanese patients. In the present study, we sought to determine whether this SNP is predictive of HCC development in the Caucasian population as well., Methods: An extended region around rs2596542 was genotyped in 1924 HCV-infected patients from the Swiss Hepatitis C Cohort Study (SCCS). Pair-wise correlation between key SNPs was calculated both in the Japanese and European populations (HapMap3: CEU and JPT)., Results: To our surprise, the minor allele A of rs2596542 in proximity of MICA appeared to have a protective impact on HCC development in Caucasians, which represents an inverse association as compared to the one observed in the Japanese population. Detailed fine-mapping analyses revealed a new SNP in HCP5 (rs2244546) upstream of MICA as strong predictor of HCV-related HCC in the SCCS (univariable p=0.027; multivariable p=0.0002, odds ratio=3.96, 95% confidence interval=1.90-8.27). This newly identified SNP had a similarly directed effect on HCC in both Caucasian and Japanese populations, suggesting that rs2244546 may better tag a putative true variant than the originally identified SNPs., Conclusions: Our data confirms the MICA/HCP5 region as susceptibility locus for HCV-related HCC and identifies rs2244546 in HCP5 as a novel tagging SNP. In addition, our data exemplify the need for conducting meta-analyses of cohorts of different ethnicities in order to fine map GWAS signals., (Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
Published: 2013
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31. Multicenter evaluation of the Elecsys® anti-HCV II assay for the diagnosis of hepatitis C virus infection.

Author: Esteban JI, van Helden J, Alborino F, Bürgisser P, Cellerai C, Pantaleo G, Eiras A, Rodriguez MI, Ghisetti V, Gleich M, Imdahl R, Kaiser C, Möller P, Wetlitzky O, Segovia M, Schennach H, and Mühlbacher A
Subjects: Female, Humans, Immunoassay methods, Male, Pregnancy, Sensitivity and Specificity, Clinical Laboratory Techniques methods, Hepacivirus immunology, Hepatitis C diagnosis, Hepatitis C Antibodies blood
Abstract: Routine screening of patients at risk of hepatitis C virus (HCV) infection has become a priority given recent improvements in therapeutic options and the asymptomatic nature of most chronic infections. The aim of this study was to evaluate the performance of the Elecsys® Anti-HCV II assay, a new qualitative antibody immunoassay, compared with currently available assays, and assess its suitability for routine diagnostic testing. The sensitivity of the Elecsys® Anti-HCV II, ARCHITECT® Anti-HCV, AxSYM® HCV 3.0, PRISM® HCV, Vitros® ECi Anti-HCV, Elecsys® Anti-HCV, and ADVIA Centaur® HCV assays was compared using commercially available seroconversion panels and samples from patients known to be HCV positive and infected with HCV genotypes 1-6. Specificity was investigated using samples from blood donors, unselected hospitalized patients, and patients with potential cross-reacting factors or from high-risk groups. The Elecsys® Anti-HCV II assay detected more positive bleeds than the comparator assays, was more sensitive in recognizing early HCV infection, and correctly identified all 765 samples known to be HCV positive, regardless of genotype. The overall specificity of the Elecsys(®) Anti-HCV II assay was 99.84% (n=6,850) using blood donor samples, 99.66% (n=3,922) using samples from unselected hospitalized patients, and 99.66% (n=2,397) using samples from patients with potentially cross-reacting factors or from high-risk groups. The specificity of the Elecsys® Anti-HCV II assay was superior or equal to the comparator assays. In conclusion, the Elecsys® Anti-HCV II assay is a sensitive and specific assay suitable for routine use in the reliable detection of anti-HCV antibodies., (Copyright © 2013 Wiley Periodicals, Inc.)
Published: 2013
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32. Rapid perturbation in viremia levels drives increases in functional avidity of HIV-specific CD8 T cells.

Author: Viganò S, Bellutti Enders F, Miconnet I, Cellerai C, Savoye AL, Rozot V, Perreau M, Faouzi M, Ohmiti K, Cavassini M, Bart PA, Pantaleo G, and Harari A
Subjects: Anti-Retroviral Agents therapeutic use, Antibody Affinity, CD8-Positive T-Lymphocytes drug effects, CD8-Positive T-Lymphocytes metabolism, Chronic Disease, Cohort Studies, Cross-Sectional Studies, Cyclosporine therapeutic use, Disease Progression, Epitope Mapping, HIV drug effects, HIV growth & development, HIV isolation & purification, HIV Infections blood, HIV Infections drug therapy, HIV Infections virology, Humans, Immunosuppressive Agents therapeutic use, Longitudinal Studies, Receptors, Antigen, T-Cell chemistry, Receptors, Antigen, T-Cell metabolism, Up-Regulation drug effects, Viremia blood, Viremia drug therapy, Viremia virology, Virus Replication drug effects, Antibodies, Viral analysis, CD8-Positive T-Lymphocytes immunology, HIV immunology, HIV Infections immunology, Immunity, Cellular drug effects, Receptors, Antigen, T-Cell biosynthesis, Viremia immunology
Abstract: The factors determining the functional avidity and its relationship with the broad heterogeneity of antiviral T cell responses remain partially understood. We investigated HIV-specific CD8 T cell responses in 85 patients with primary HIV infection (PHI) or chronic (progressive and non-progressive) infection. The functional avidity of HIV-specific CD8 T cells was not different between patients with progressive and non-progressive chronic infection. However, it was significantly lower in PHI patients at the time of diagnosis of acute infection and after control of virus replication following one year of successful antiretroviral therapy. High-avidity HIV-specific CD8 T cells expressed lower levels of CD27 and CD28 and were enriched in cells with an exhausted phenotype, i.e. co-expressing PD-1/2B4/CD160. Of note, a significant increase in the functional avidity of HIV-specific CD8 T cells occurred in early-treated PHI patients experiencing a virus rebound after spontaneous treatment interruption. This increase in functional avidity was associated with the accumulation of PD-1/2B4/CD160 positive cells, loss of polyfunctionality and increased TCR renewal. The increased TCR renewal may provide the mechanistic basis for the generation of high-avidity HIV-specific CD8 T cells. These results provide insights on the relationships between functional avidity, viremia, T-cell exhaustion and TCR renewal of antiviral CD8 T cell responses.
Published: 2013
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33. The individualized genetic barrier predicts treatment response in a large cohort of HIV-1 infected patients.

Author: Beerenwinkel N, Montazeri H, Schuhmacher H, Knupfer P, von Wyl V, Furrer H, Battegay M, Hirschel B, Cavassini M, Vernazza P, Bernasconi E, Yerly S, Böni J, Klimkait T, Cellerai C, and Günthard HF
Subjects: Adult, Bayes Theorem, Cohort Studies, Drug Resistance, Viral, Female, HIV Infections virology, Humans, Logistic Models, Male, Middle Aged, Models, Genetic, Models, Statistical, Odds Ratio, ROC Curve, Treatment Outcome, Anti-HIV Agents therapeutic use, HIV Infections drug therapy, HIV Infections genetics, HIV-1, Models, Biological
Abstract: The success of combination antiretroviral therapy is limited by the evolutionary escape dynamics of HIV-1. We used Isotonic Conjunctive Bayesian Networks (I-CBNs), a class of probabilistic graphical models, to describe this process. We employed partial order constraints among viral resistance mutations, which give rise to a limited set of mutational pathways, and we modeled phenotypic drug resistance as monotonically increasing along any escape pathway. Using this model, the individualized genetic barrier (IGB) to each drug is derived as the probability of the virus not acquiring additional mutations that confer resistance. Drug-specific IGBs were combined to obtain the IGB to an entire regimen, which quantifies the virus' genetic potential for developing drug resistance under combination therapy. The IGB was tested as a predictor of therapeutic outcome using between 2,185 and 2,631 treatment change episodes of subtype B infected patients from the Swiss HIV Cohort Study Database, a large observational cohort. Using logistic regression, significant univariate predictors included most of the 18 drugs and single-drug IGBs, the IGB to the entire regimen, the expert rules-based genotypic susceptibility score (GSS), several individual mutations, and the peak viral load before treatment change. In the multivariate analysis, the only genotype-derived variables that remained significantly associated with virological success were GSS and, with 10-fold stronger association, IGB to regimen. When predicting suppression of viral load below 400 cps/ml, IGB outperformed GSS and also improved GSS-containing predictors significantly, but the difference was not significant for suppression below 50 cps/ml. Thus, the IGB to regimen is a novel data-derived predictor of treatment outcome that has potential to improve the interpretation of genotypic drug resistance tests.
Published: 2013
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34. Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M.

Author: Scherrer AU, von Wyl V, Götte M, Klimkait T, Cellerai C, Yerly S, Böni J, Held L, Ledergerber B, and Günthard HF
Subjects: Amino Acid Substitution genetics, Anti-HIV Agents pharmacology, Cohort Studies, Gene Frequency, HIV Infections drug therapy, HIV Infections virology, HIV-1 drug effects, Humans, Logistic Models, Mutagenesis, Insertional, Nucleosides genetics, Switzerland, Thymidine genetics, Drug Resistance, Multiple, Viral genetics, HIV Infections genetics, HIV Reverse Transcriptase genetics, HIV-1 genetics, Mutation, Thymidine analogs & derivatives
Abstract: Background: We hypothesized that polymorphic mutations exist that are associated with the emergence of the multinucleoside resistance mutations (MNR), 69 insertion and Q151M., Methods: The Swiss HIV Cohort Study was screened, and the frequencies of polymorphic mutations in HIV-1 (subtype B) were compared between patients detected with the 69 insertion (n = 17), Q151M (n = 29), ≥2 thymidine analogue mutations (TAM) 1 (n = 400) or ≥2 TAM 2 (n = 249). Logistic regressions adjusted for the antiretroviral treatment history were performed to analyze the association of the polymorphic mutations with MNR., Results: The 69 insertion and TAM 1 were strongly associated and occurred in 94.1% (16 of 17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared with 4.4 for ≥2 TAM 1, P Wilcoxon = 0.009). Frequencies of 8 polymorphic mutations (K43E, V60I, S68G, S162C, T165I, I202V, R211K, F214L) were significantly different between groups. Logistic regression showed that F214L and V60I were associated with the emergence of Q151M/TAM 2 opposed to 69 insertion/TAM 1. S68G, T165I, and I202V were associated with Q151M instead of TAM 2., Conclusions: Besides antiretroviral therapy, polymorphic mutations may contribute to the emergence of specific MNR mutations.
Published: 2012
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35. HIV testing practices by clinical service before and after revised testing guidelines in a Swiss University Hospital.

Author: Darling KE, Hugli O, Mamin R, Cellerai C, Martenet S, Berney A, Peters S, Du Pasquier RA, Bodenmann P, and Cavassini M
Subjects: Databases, Factual, Female, HIV Seropositivity diagnosis, Humans, Male, Switzerland, HIV Infections diagnosis, Hospitals, University standards, Mass Screening standards, Practice Guidelines as Topic standards
Abstract: Objectives: To determine 1) HIV testing practices in a 1400-bed university hospital where local HIV prevalence is 0.4% and 2) the effect on testing practices of national HIV testing guidelines, revised in March 2010, recommending Physician-Initiated Counselling and Testing (PICT)., Methods: Using 2 hospital databases, we determined the number of HIV tests performed by selected clinical services, and the number of patients tested as a percentage of the number seen per service ('testing rate'). To explore the effect of the revised national guidelines, we examined testing rates for two years pre- and two years post-PICT guideline publication., Results: Combining the clinical services, 253,178 patients were seen and 9,183 tests were performed (of which 80 tested positive, 0.9%) in the four-year study period. The emergency department (ED) performed the second highest number of tests, but had the lowest testing rates (0.9-1.1%). Of inpatient services, neurology and psychiatry had higher testing rates than internal medicine (19.7% and 9.6% versus 8%, respectively). There was no significant increase in testing rates, either globally or in the majority of the clinical services examined, and no increase in new HIV diagnoses post-PICT recommendations., Conclusions: Using a simple two-database tool, we observe no global improvement in HIV testing rates in our hospital following new national guidelines but do identify services where testing practices merit improvement. This study may show the limit of PICT strategies based on physician risk assessment, compared to the opt-out approach.
Published: 2012
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36. Minor protease inhibitor mutations at baseline do not increase the risk for a virological failure in HIV-1 subtype B infected patients.

Author: Scherrer AU, Ledergerber B, von Wyl V, Böni J, Yerly S, Klimkait T, Cellerai C, Furrer H, Calmy A, Cavassini M, Elzi L, Vernazza PL, Bernasconi E, and Günthard HF
Subjects: CD4 Lymphocyte Count, Female, HIV Infections virology, HIV Protease Inhibitors therapeutic use, Humans, Male, RNA, Viral blood, Viral Load, Drug Resistance, Viral genetics, HIV Infections drug therapy, HIV Protease genetics, HIV Protease Inhibitors pharmacology, Mutation
Abstract: Background: Minor protease inhibitor (PI) mutations often exist as polymorphisms in HIV-1 sequences from treatment-naïve patients. Previous studies showed that their presence impairs the antiretroviral treatment (ART) response. Evaluating these findings in a larger cohort is essential., Methods: To study the impact of minor PI mutations on time to viral suppression and time to virological failure, we included patients from the Swiss HIV Cohort Study infected with HIV-1 subtype B who started first-line ART with a PI and two nucleoside reverse transcriptase inhibitors. Cox regression models were performed to compare the outcomes among patients with 0 and ≥ 1 minor PI mutation. Models were adjusted for baseline HIV-1 RNA, CD4 cell count, sex, transmission category, age, ethnicity, year of ART start, the presence of nucleoside reverse transcriptase inhibitor mutations, and stratified for the administered PIs., Results: We included 1199 patients of whom 944 (78.7%) received a boosted PI. Minor PI mutations associated with the administered PI were common: 41.7%, 16.1%, 4.7% and 1.9% had 1, 2, 3 or ≥ 4 mutations, respectively. The time to viral suppression was similar between patients with 0 (reference) and ≥ 1 minor PI mutation (multivariable hazard ratio (HR): 1.1 [95% confidence interval (CI): 1.0-1.3], P = .196). The time to virological failure was also similar (multivariable HR:.9 [95% CI:.5-1.6], P = .765). In addition, the impact of each single minor PI mutation was analyzed separately: none was significantly associated with the treatment outcome., Conclusions: The presence of minor PI mutations at baseline has no effect on the therapy outcome in HIV infected individuals.
Published: 2012
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37. Inferring epidemic contact structure from phylogenetic trees.

Author: Leventhal GE, Kouyos R, Stadler T, Wyl Vv, Yerly S, Böni J, Cellerai C, Klimkait T, Günthard HF, and Bonhoeffer S
Subjects: Female, Humans, Male, Phylogeny, Prevalence, Risk Assessment methods, Risk Factors, Switzerland epidemiology, Contact Tracing methods, Disease Transmission, Infectious statistics & numerical data, Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, HIV Infections epidemiology, HIV Infections genetics, Proportional Hazards Models
Abstract: Contact structure is believed to have a large impact on epidemic spreading and consequently using networks to model such contact structure continues to gain interest in epidemiology. However, detailed knowledge of the exact contact structure underlying real epidemics is limited. Here we address the question whether the structure of the contact network leaves a detectable genetic fingerprint in the pathogen population. To this end we compare phylogenies generated by disease outbreaks in simulated populations with different types of contact networks. We find that the shape of these phylogenies strongly depends on contact structure. In particular, measures of tree imbalance allow us to quantify to what extent the contact structure underlying an epidemic deviates from a null model contact network and illustrate this in the case of random mixing. Using a phylogeny from the Swiss HIV epidemic, we show that this epidemic has a significantly more unbalanced tree than would be expected from random mixing.
Published: 2012
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38. Assessing predicted HIV-1 replicative capacity in a clinical setting.

Author: Kouyos RD, von Wyl V, Hinkley T, Petropoulos CJ, Haddad M, Whitcomb JM, Böni J, Yerly S, Cellerai C, Klimkait T, Günthard HF, and Bonhoeffer S
Subjects: Adult, Anti-HIV Agents pharmacology, Artificial Intelligence, Base Sequence, Computer Simulation, Drug Resistance, Viral genetics, Female, Genotype, HIV-1 drug effects, HIV-1 genetics, Humans, Male, Microbial Sensitivity Tests, Viremia, Genes, pol, HIV Infections virology, HIV-1 physiology, Viral Load, Virus Replication genetics
Abstract: HIV-1 replicative capacity (RC) provides a measure of within-host fitness and is determined in the context of phenotypic drug resistance testing. However it is unclear how these in-vitro measurements relate to in-vivo processes. Here we assess RCs in a clinical setting by combining a previously published machine-learning tool, which predicts RC values from partial pol sequences with genotypic and clinical data from the Swiss HIV Cohort Study. The machine-learning tool is based on a training set consisting of 65000 RC measurements paired with their corresponding partial pol sequences. We find that predicted RC values (pRCs) correlate significantly with the virus load measured in 2073 infected but drug naïve individuals. Furthermore, we find that, for 53 pairs of sequences, each pair sampled in the same infected individual, the pRC was significantly higher for the sequence sampled later in the infection and that the increase in pRC was also significantly correlated with the increase in plasma viral load and with the length of the time-interval between the sampling points. These findings indicate that selection within a patient favors the evolution of higher replicative capacities and that these in-vitro fitness measures are indicative of in-vivo HIV virus load.
Published: 2011
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39. Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors.

Author: Cellerai C, Harari A, Stauss H, Yerly S, Geretti AM, Carroll A, Yee T, Ainsworth J, Williams I, Sweeney J, Freedman A, Johnson M, Pantaleo G, and Kinloch-de Loes S
Subjects: Adult, Aged, Anti-HIV Agents therapeutic use, CD4 Antigens metabolism, CD8 Antigens metabolism, Cohort Studies, Epitopes immunology, Female, Gene Expression Regulation drug effects, Genotype, HIV Infections blood, HIV Infections drug therapy, HIV Infections genetics, HIV Infections immunology, HIV-1 physiology, Histocompatibility Antigens Class I genetics, Humans, Male, Middle Aged, Perforin metabolism, Species Specificity, T-Lymphocytes immunology, T-Lymphocytes metabolism, Time Factors, Virus Replication drug effects, gag Gene Products, Human Immunodeficiency Virus immunology, Anti-HIV Agents pharmacology, HIV Long-Term Survivors, HIV-1 drug effects, HIV-1 immunology, T-Lymphocytes drug effects, T-Lymphocytes virology
Abstract: Background: Intervention with antiretroviral treatment (ART) and control of viral replication at the time of HIV-1 seroconversion may curtail cumulative immunological damage. We have therefore hypothesized that ART maintenance over a very prolonged period in HIV-1 seroconverters could induce an immuno-virological status similar to that of HIV-1 long-term non-progressors (LTNPs)., Methodology/principal Findings: We have investigated a cohort of 20 HIV-1 seroconverters on long-term ART (LTTS) and compared it to one of 15 LTNPs. Residual viral replication and reservoirs in peripheral blood, as measured by cell-associated HIV-1 RNA and DNA, respectively, were demonstrated to be similarly low in both cohorts. These two virologically matched cohorts were then comprehensively analysed by polychromatic flow cytometry for HIV-1-specific CD4(+) and CD8(+) T-cell functional profile in terms of cytokine production and cytotoxic capacity using IFN-γ, IL-2, TNF-α production and perforin expression, respectively. Comparable levels of highly polyfunctional HIV-1-specific CD4(+) and CD8(+) T-cells were found in LTTS and LTNPs, with low perforin expression on HIV-1-specific CD8(+) T-cells, consistent with a polyfunctional/non-cytotoxic profile in a context of low viral burden., Conclusions: Our results indicate that prolonged ART initiated at the time of HIV-1 seroconversion is associated with immuno-virological features which resemble those of LTNPs, strengthening the recent emphasis on the positive impact of early treatment initiation and paving the way for further interventions to promote virological control after treatment interruption.
Published: 2011
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40. Proliferation capacity and cytotoxic activity are mediated by functionally and phenotypically distinct virus-specific CD8 T cells defined by interleukin-7R{alpha} (CD127) and perforin expression.

Author: Cellerai C, Perreau M, Rozot V, Bellutti Enders F, Pantaleo G, and Harari A
Subjects: Cell Degranulation, Cells, Cultured, Flow Cytometry, Humans, Interferon-gamma biosynthesis, Interleukin-2 biosynthesis, Tumor Necrosis Factor-alpha biosynthesis, CD8-Positive T-Lymphocytes immunology, Cell Proliferation, Cytotoxicity, Immunologic, Interleukin-7 Receptor alpha Subunit biosynthesis, Perforin biosynthesis, T-Lymphocyte Subsets immunology, Virus Diseases immunology
Abstract: Cytotoxicity and proliferation capacity are key functions of antiviral CD8 T cells. In the present study, we investigated a series of markers to define these functions in virus-specific CD8 T cells. We provide evidence that there is a lack of coexpression of perforin and CD127 in human CD8 T cells. CD127 expression on virus-specific CD8 T cells correlated positively with proliferation capacity and negatively with perforin expression and cytotoxicity. Influenza virus-, cytomegalovirus-, and Epstein-Barr virus/human immunodeficiency virus type 1-specific CD8 T cells were predominantly composed of CD127(+) perforin(-)/CD127(-) perforin(+), and CD127(-)/perforin(-) CD8 T cells, respectively. CD127(-)/perforin(-) and CD127(-)/perforin(+) cells expressed significantly more PD-1 and CD57, respectively. Consistently, intracellular cytokine (gamma interferon, tumor necrosis factor alpha, and interleukin-2 [IL-2]) responses combined to perforin detection confirmed that virus-specific CD8 T cells were mostly composed of either perforin(+)/IL-2(-) or perforin(-)/IL-2(+) cells. In addition, perforin expression and IL-2 secretion were negatively correlated in virus-specific CD8 T cells (P < 0.01). As previously shown for perforin, changes in antigen exposure modulated also CD127 expression. Based on the above results, proliferating (CD127(+)/IL-2-secreting) and cytotoxic (perforin(+)) CD8 T cells were contained within phenotypically distinct T-cell populations at different stages of activation or differentiation and showed different levels of exhaustion and senescence. Furthermore, the composition of proliferating and cytotoxic CD8 T cells for a given antiviral CD8 T-cell population appeared to be influenced by antigen exposure. These results advance our understanding of the relationship between cytotoxicity, proliferation capacity, the levels of senescence and exhaustion, and antigen exposure of antiviral memory CD8 T cells.
Published: 2010
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41. Distinct profiles of cytotoxic granules in memory CD8 T cells correlate with function, differentiation stage, and antigen exposure.

Author: Harari A, Bellutti Enders F, Cellerai C, Bart PA, and Pantaleo G
Subjects: CD8-Positive T-Lymphocytes chemistry, Cytomegalovirus immunology, Granzymes biosynthesis, HIV-1 immunology, Herpesvirus 4, Human immunology, Humans, Interleukin-7 Receptor alpha Subunit analysis, Leukocyte Common Antigens analysis, Orthomyxoviridae immunology, Perforin biosynthesis, T-Lymphocyte Subsets chemistry, T-Lymphocyte Subsets immunology, CD8-Positive T-Lymphocytes immunology, Cytoplasmic Granules immunology
Abstract: Cytotoxic CD8 T cells exert their antiviral and antitumor activity primarily through the secretion of cytotoxic granules. Degranulation activity and cytotoxic granules (perforin plus granzymes) generally define CD8 T cells with cytotoxic function. In this study, we have investigated the expression of granzyme K (GrmK) in comparison to that of GrmA, GrmB, and perforin. The expression of the cytotoxic granules was assessed in virus-specific CD8 T cells specific to influenza virus, Epstein-Barr virus (EBV), cytomegalovirus (CMV), or human immunodeficiency virus type 1 (HIV-1). We observed a dichotomy between GrmK and perforin expression in virus-specific CD8 T cells. The profile in influenza virus-specific CD8 T cells was perforin(-) GrmB(-) GrmA(+/-) GrmK(+); in CMV-specific cells, it was perforin(+) GrmB(+) GrmA(+) GrmK(-/+); and in EBV- and HIV-1-specific cells, it was perforin(-/+) GrmB(+) GrmA(+) GrmK(+). On the basis of the delineation of memory and effector CD8 T cells with CD45RA and CD127, the GrmK(+) profile was associated with early-stage memory CD8 T-cell differentiation, the perforin(+) GrmB(+) GrmA(+) profile with advanced-stage differentiation, and the GrmB(+) GrmA(+) Grmk(+) profile with intermediate-stage differentiation. Furthermore, perforin and GrmB but not GrmA and GrmK correlated with cytotoxic activity. Finally, changes in antigen exposure in vitro and in vivo during primary HIV-1 infection and vaccination modulated cytotoxic granule profiles. These results advance our understanding of the relationship between distinct profiles of cytotoxic granules in memory CD8 T cells and function, differentiation stage, and antigen exposure.
Published: 2009
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42. EV02: a Phase I trial to compare the safety and immunogenicity of HIV DNA-C prime-NYVAC-C boost to NYVAC-C alone.

Author: McCormack S, Stöhr W, Barber T, Bart PA, Harari A, Moog C, Ciuffreda D, Cellerai C, Cowen M, Gamboni R, Burnet S, Legg K, Brodnicki E, Wolf H, Wagner R, Heeney J, Frachette MJ, Tartaglia J, Babiker A, Pantaleo G, and Weber J
Subjects: AIDS Vaccines administration & dosage, AIDS Vaccines immunology, Adult, Antigens, Viral biosynthesis, Antigens, Viral genetics, Drug Design, Female, HIV Infections immunology, HIV-1 classification, HIV-1 genetics, HIV-1 immunology, Humans, Immunization, Secondary, Injections, Intramuscular, Male, Safety, Viral Vaccines administration & dosage, env Gene Products, Human Immunodeficiency Virus genetics, AIDS Vaccines therapeutic use, Antigens, Viral immunology, HIV Infections prevention & control, Viral Vaccines chemistry, Viral Vaccines immunology
Abstract: The aim of this randomised controlled trial was to see if the addition of 4 mg/ml DNA-C priming given by the intramuscular route at weeks 0 and 4 to NYVAC-C at weeks 20 and 24, safely increased the proportion of participants with HIV-specific T-cell responses measured by the interferon (IFN)-gamma ELISpot assay at weeks 26 and/or 28 compared to NYVAC-C alone. Although 2 individuals discontinued after the first DNA-C due to adverse events (1 vaso-vagal; 1 transient, asymptomatic elevation in alanine transaminase), the vaccines were well tolerated. Three others failed to complete the regimen (1 changed her mind; 2 lost to follow-up). Of the 35 that completed the regimen 90% (18/20) in the DNA-C group had ELISpot responses compared to 33% (5/15) that received NYVAC-C alone (p=0.001). Responses were to envelope in the majority (21/23). Of the 9 individuals with responses to envelope and other peptides, 8 were in the DNA-C group. These promising results suggest that DNA-C was an effective priming agent, that merits further investigation.
Published: 2008
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43. An HIV-1 clade C DNA prime, NYVAC boost vaccine regimen induces reliable, polyfunctional, and long-lasting T cell responses.

Author: Harari A, Bart PA, Stöhr W, Tapia G, Garcia M, Medjitna-Rais E, Burnet S, Cellerai C, Erlwein O, Barber T, Moog C, Liljestrom P, Wagner R, Wolf H, Kraehenbuhl JP, Esteban M, Heeney J, Frachette MJ, Tartaglia J, McCormack S, Babiker A, Weber J, and Pantaleo G
Subjects: AIDS Vaccines chemistry, Animals, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, Codon, Enzyme-Linked Immunosorbent Assay methods, Epitope Mapping, Humans, Peptides chemistry, Phenotype, Vaccines, Viral Vaccines chemistry, env Gene Products, Human Immunodeficiency Virus genetics, gag Gene Products, Human Immunodeficiency Virus genetics, nef Gene Products, Human Immunodeficiency Virus genetics, AIDS Vaccines therapeutic use, Viral Vaccines therapeutic use
Abstract: The EuroVacc 02 phase I trial has evaluated the safety and immunogenicity of a prime-boost regimen comprising recombinant DNA and the poxvirus vector NYVAC, both expressing a common immunogen consisting of Env, Gag, Pol, and Nef polypeptide domain from human immunodeficiency virus (HIV)-1 clade C isolate, CN54. 40 volunteers were randomized to receive DNA C or nothing on day 0 and at week 4, followed by NYVAC C at weeks 20 and 24. The primary immunogenicity endpoints were measured at weeks 26 and 28 by the quantification of T cell responses using the interferon gamma enzyme-linked immunospot assay. Our results indicate that the DNA C plus NYVAC C vaccine regimen was highly immunogenic, as indicated by the detection of T cell responses in 90% of vaccinees and was superior to responses induced by NYVAC C alone (33% of responders). The vaccine-induced T cell responses were (a) vigorous in the case of the env response (mean 480 spot-forming units/10(6) mononuclear cells at weeks 26/28), (b) polyfunctional for both CD4 and CD8 T cell responses, (c) broad (the average number of epitopes was 4.2 per responder), and (d) durable (T cell responses were present in 70% of vaccinees at week 72). The vaccine-induced T cell responses were strongest and most frequently directed against Env (91% of vaccines), but smaller responses against Gag-Pol-Nef were also observed in 48% of vaccinees. These results support the development of the poxvirus platform in the HIV vaccine field and the further clinical development of the DNA C plus NYVAC C vaccine regimen.
Published: 2008
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44. Treatment of acute HIV-1 infection: are we getting there?

Author: Cellerai C, Little SJ, and Loes SK
Abstract: Purpose of Review: Treatment of primary HIV-1 infection may alter the natural history of HIV-1 infection and delay the need for chronic antiretroviral therapy; it may also be a public health measure. We discuss the results of therapeutic trials and cohort studies, the occurrence of transmitted drug resistance, and recent findings in terms of immunopathogenesis and decay of viral reservoirs., Recent Findings: Events at the time of primary HIV-1 infection are understood to set the scene for persistence of immunologic damage and chronic immune activation, with a rapid viral onslaught primarily on memory CD4 T cells at mucosal effector sites. The initiation of antiretroviral therapy at primary HIV-1 infection has been associated with a high degree of undetectable viremia in compliant patients and substantial decay of reservoirs in peripheral blood. The degree of immune reconstitution at the gut mucosal level, however, does not appear to be comparable to that in peripheral blood., Summary: Recent insights into the long-term consequences of the early burst of HIV-1 replication - together with transmitted drug resistance, onward transmission, and the possibility of decay of viral reservoirs - are important steps in helping to design future therapeutic strategies in primary HIV-1 infection in an era of intense drug and vaccine development.
Published: 2008
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45. Skewed association of polyfunctional antigen-specific CD8 T cell populations with HLA-B genotype.

Author: Harari A, Cellerai C, Bellutti Enders F, Köstler J, Codarri L, Tapia G, Boyman O, Castro E, Gaudieri S, James I, John M, Wagner R, Mallal S, and Pantaleo G
Subjects: Cohort Studies, Cytomegalovirus immunology, Genotype, HIV Infections genetics, HIV-1 immunology, HLA-A Antigens genetics, Herpesvirus 4, Human immunology, Humans, In Vitro Techniques, Interleukin-2 biosynthesis, Lymphocyte Activation, Orthomyxoviridae immunology, Receptors, Antigen, T-Cell metabolism, CD8-Positive T-Lymphocytes immunology, HIV Infections immunology, HLA-B Antigens genetics
Abstract: We studied CD8 T cell responses against HIV-1, cytomegalovirus, Epstein-Barr virus, and influenza in 128 subjects and demonstrate that polyfunctional CD8 T cell responses, also including IL-2 production and Ag-specific proliferation, are predominantly driven by virus epitopes restricted by HLA-B alleles. Interestingly, these protective CD8 T cells are equipped with low-avidity T cell receptors (TCRs) for the cognate virus epitope. Conversely, HLA-A-restricted epitopes are mostly associated with "only effector" IFN-gamma-secreting, with cytotoxicity, and with the lack of IL-2 production and Ag-specific proliferation. These CD8 T cells are equipped with high-avidity TCR and express higher levels of the T cell exhaustion marker PD-1. Thus, the functional profile of the CD8 T cell response is strongly influenced by the extent to which there is stimulation of polyfunctional (predominantly restricted by HLA-B) versus only effector (restricted by HLA-A) T cell responses. These results provide the rationale for the observed protective role of HLA-B in HIV-1-infection and new insights into the relationship between TCR avidity, PD-1 expression, and the functional profile of CD8 T cells.
Published: 2007
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46. Functional and phenotypic characterization of tetanus toxoid-specific human CD4+ T cells following re-immunization.

Author: Cellerai C, Harari A, Vallelian F, Boyman O, and Pantaleo G
Subjects: CD4-Positive T-Lymphocytes metabolism, Cells, Cultured, Cytokines metabolism, Epitopes, T-Lymphocyte administration & dosage, Humans, Immunologic Memory, Tetanus Toxoid administration & dosage, CD4-Positive T-Lymphocytes immunology, Epitopes, T-Lymphocyte immunology, Immunization, Secondary, Immunophenotyping, Tetanus Toxoid immunology
Abstract: The formation of immunological memory is a hallmark of adaptive immunity and the goal of vaccination. For CD8(+ )T cells, successful generation of memory cells has been linked to IL-7 receptor alpha (IL-7Ralpha) expression, suggesting a role for IL-7 signaling, which in turn is important for preventing T cell apoptosis. We thus investigated the kinetics and changes of IL-7Ralpha and anti-apoptotic protein Bcl-2 expression levels in tetanus toxoid (TT)-specific CD4(+ )T cells at different time points prior and after TT re-immunization of TT-immune individuals. Prior to re-immunization, most TT-specific CD4(+ )T cells were high IL-2 producers, CD45RA(-)CCR7(+), IL-7Ralpha(high)Bcl-2(high) cells, resembling typical long-lived central memory cells. Already 5 days, and more importantly at the peak of the response, after TT re-immunization, a substantial fraction of these cells secreted also IFN-gamma, down-regulated CCR7, IL-7Ralpha and Bcl-2 and became Ki67 positive, resembling effector memory cells. In contrast, TT-specific CD4(+ )T cells found 60 days or later after re-immunization were again as baseline. Interestingly, a significant fraction of IL-7Ralpha(high)Bcl-2(high) TT-specific CD4(+ )T cells, i.e. the proposed memory cell precursors, remained stable at any time point upon re-immunization. Together, these results suggest that IL-7Ralpha expression levels might be a useful marker for identifying long-lived Ag-specific CD4(+ )T cells in memory T cells.
Published: 2007
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47. Functional signatures of protective antiviral T-cell immunity in human virus infections.

Author: Harari A, Dutoit V, Cellerai C, Bart PA, Du Pasquier RA, and Pantaleo G
Subjects: Acute Disease, Chronic Disease, Humans, Immunity, Cellular immunology, Lymphocyte Activation, Virus Diseases virology, CD4-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes immunology, Virus Diseases immunology
Abstract: The most common human viruses have different abilities to establish persistent chronic infection. Virus-specific T-cell responses are critical in the control of virus replication and in the prevention of disease in chronic infection. A large number of phenotypic markers and a series of functions have been used to characterize virus-specific CD4+ and CD8+ T-cell responses, and these studies have shown great phenotypic and functional heterogeneity of the T-cell responses against different viruses. The heterogeneity of the T-cell response has been proposed to be specific to each virus. However, over the past 2 years, several studies have provided evidence that the phenotypic and functional heterogeneity of CD4+ and CD8+ T-cell responses is predominantly regulated by the levels of antigen load. The levels of antigen load modulate the phenotypic and functional patterns of the T-cell response within the same virus infection. Furthermore, the functional characterization of virus-specific CD4+ and CD8+ T-cell responses has identified signatures of protective antiviral immunity. Polyfunctional, i.e. interleukin-2 and interferon-gamma (IFN-gamma) secretion and proliferation, and not monofunctional, i.e. IFN-gamma secretion, CD4+ and CD8+ T-cell responses represent correlates of protective antiviral immunity in chronic virus infections.
Published: 2006
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48. Role of HIV-1-specific CD4 T cells.

Author: Harari A, Cellerai C, and Pantaleo G
Abstract: Purpose of Review: Most of the studies investigating antiviral immunity have predominantly focused on CD8 T cells. However, numerous recent studies have highlighted the importance of HIV-1-specific CD4 T cells in the antiviral immune response, and have also revealed the high level of complexity and heterogeneity of the virus-specific CD4 T-cell responses. An understanding of the role of these key players in the antiviral immune response is of fundamental importance., Recent Findings: A comprehensive investigation of several features of virus-specific CD4 T-cell responses, including the magnitude, breadth, function and phenotype, has recently been performed. In particular, HIV-1-specific CD4 T-cell responses have been studied in different stages of HIV-1 infection, i.e. acute and chronic phase, under conditions of spontaneous (long-term non-progressors) or antiviral therapy-mediated control of virus replication or uncontrolled virus replication. Different phenotypical and functional patterns of HIV-1-specific CD4 T-cell responses were associated with different conditions of controlled versus uncontrolled virus replication, thus allowing the identification of signatures of protective immune responses. Robust and diverse virus-specific CD4 T-cell responses have been observed. These responses, however, were not predictive of nonprogressive versus progressive HIV-1-associated disease., Summary: There is an urgent need to delineate the immune correlates of protective T-cell responses in order to develop novel immunological markers to evaluate the degree of immune restoration of antiviral therapy as well as the potential effectiveness of HIV vaccine-induced T-cell immune responses.
Published: 2006
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49. HIV-1-specific IFN-gamma/IL-2-secreting CD8 T cells support CD4-independent proliferation of HIV-1-specific CD8 T cells.

Author: Zimmerli SC, Harari A, Cellerai C, Vallelian F, Bart PA, and Pantaleo G
Subjects: CD4 Antigens immunology, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes virology, Cytomegalovirus immunology, Flow Cytometry, Herpesvirus 4, Human immunology, Humans, Leukocyte Common Antigens metabolism, Orthomyxoviridae immunology, Receptors, CCR7, Receptors, Chemokine metabolism, CD8-Positive T-Lymphocytes metabolism, Cell Proliferation, HIV Infections immunology, HIV-1, Interferon-gamma metabolism, Interleukin-2 metabolism
Abstract: Functional and phenotypic characterization of virus-specific CD8 T cells against cytomegalovirus, Epstein-Barr virus, influenza (flu), and HIV-1 were performed on the basis of the ability of CD8 T cells to secrete IFN-gamma and IL-2, to proliferate, and to express CD45RA and CCR7. Two functional distinct populations of CD8 T cells were identified: (i) dual IFN-gamma/IL-2-secreting cells and (ii) single IFN-gamma-secreting cells. Virus-specific IFN-gamma/IL-2-secreting CD8 T cells were CD45RA-CCR7-, whereas single IFN-gamma CD8 T cells were either CD45RA-CCR7- or CD45RA+CCR7-. The proportion of virus-specific IFN-gamma/IL-2-secreting CD8 T cells correlated with that of proliferating CD8 T cells, and the loss of HIV-1-specific IL-2-secreting CD8 T cells was associated with that of HIV-1-specific CD8 T cell proliferation. Substantial proliferation of virus-specific CD8 T cells (including HIV-1-specific CD8 T cells) was also observed in CD4 T cell-depleted populations or after stimulation with MHC class I tetramer-peptide complexes. IL-2 was the factor responsible for the CD4-independent CD8 T cell proliferation. These results indicate that IFN-gamma/IL-2-secreting CD8 T cells may promote antigen-specific proliferation of CD8 T cells even in the absence of helper CD4 T cells.
Published: 2005
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