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1. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Author

Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, Ripke S, Brumme CJ, Pulit SL, Carrington M, Kadie CM, Carlson JM, Heckerman D, Graham RR, Plenge RM, Deeks SG, Gianniny L, Crawford G, Sullivan J, Gonzalez E, Davies L, Camargo A, Moore JM, Beattie N, Gupta S, Crenshaw A, Burtt NP, Guiducci C, Gupta N, Gao X, Qi Y, Yuki Y, Piechocka-Trocha A, Cutrell E, Rosenberg R, Moss KL, Lemay P, O'Leary J, Schaefer T, Verma P, Toth I, Block B, Baker B, Rothchild A, Lian J, Proudfoot J, Alvino DM, Vine S, Addo MM, Allen TM, Altfeld M, Henn MR, Le Gall S, Streeck H, Haas DW, Kuritzkes DR, Robbins GK, Shafer RW, Gulick RM, Shikuma CM, Haubrich R, Riddler S, Sax PE, Daar ES, Ribaudo HJ, Agan B, Agarwal S, Ahern RL, Allen BL, Altidor S, Altschuler EL, Ambardar S, Anastos K, Anderson B, Anderson V, Andrady U, Antoniskis D, Bangsberg D, Barbaro D, Barrie W, Bartczak J, Barton S, Basden P, Basgoz N, Bazner S, Bellos NC, Benson AM, Berger J, Bernard NF, Bernard AM, Birch C, Bodner SJ, Bolan RK, Boudreaux ET, Bradley M, Braun JF, Brndjar JE, Brown SJ, Brown K, Brown ST, Burack J, Bush LM, Cafaro V, Campbell O, Campbell J, Carlson RH, Carmichael JK, Casey KK, Cavacuiti C, Celestin G, Chambers ST, Chez N, Chirch LM, Cimoch PJ, Cohen D, Cohn LE, Conway B, Cooper DA, Cornelson B, Cox DT, Cristofano MV, Cuchural G Jr, Czartoski JL, Dahman JM, Daly JS, Davis BT, Davis K, Davod SM, DeJesus E, Dietz CA, Dunham E, Dunn ME, Ellerin TB, Eron JJ, Fangman JJ, Farel CE, Ferlazzo H, Fidler S, Fleenor-Ford A, Frankel R, Freedberg KA, French NK, Fuchs JD, Fuller JD, Gaberman J, Gallant JE, Gandhi RT, Garcia E, Garmon D, Gathe JC Jr, Gaultier CR, Gebre W, Gilman FD, Gilson I, Goepfert PA, Gottlieb MS, Goulston C, Groger RK, Gurley TD, Haber S, Hardwicke R, Hardy WD, Harrigan PR, Hawkins TN, Heath S, Hecht FM, Henry WK, Hladek M, Hoffman RP, Horton JM, Hsu RK, Huhn GD, Hunt P, Hupert MJ, Illeman ML, Jaeger H, Jellinger RM, John M, Johnson JA, Johnson KL, Johnson H, Johnson K, Joly J, Jordan WC, Kauffman CA, Khanlou H, Killian RK, Kim AY, Kim DD, Kinder CA, Kirchner JT, Kogelman L, Kojic EM, Korthuis PT, Kurisu W, Kwon DS, LaMar M, Lampiris H, Lanzafame M, Lederman MM, Lee DM, Lee JM, Lee MJ, Lee ET, Lemoine J, Levy JA, Llibre JM, Liguori MA, Little SJ, Liu AY, Lopez AJ, Loutfy MR, Loy D, Mohammed DY, Man A, Mansour MK, Marconi VC, Markowitz M, Marques R, Martin JN, Martin HL Jr, Mayer KH, McElrath MJ, McGhee TA, McGovern BH, McGowan K, McIntyre D, Mcleod GX, Menezes P, Mesa G, Metroka CE, Meyer-Olson D, Miller AO, Montgomery K, Mounzer KC, Nagami EH, Nagin I, Nahass RG, Nelson MO, Nielsen C, Norene DL, O'Connor DH, Ojikutu BO, Okulicz J, Oladehin OO, Oldfield EC 3rd, Olender SA, Ostrowski M, Owen WF Jr, Pae E, Parsonnet J, Pavlatos AM, Perlmutter AM, Pierce MN, Pincus JM, Pisani L, Price LJ, Proia L, Prokesch RC, Pujet HC, Ramgopal M, Rathod A, Rausch M, Ravishankar J, Rhame FS, Richards CS, Richman DD, Rodes B, Rodriguez M, Rose RC 3rd, Rosenberg ES, Rosenthal D, Ross PE, Rubin DS, Rumbaugh E, Saenz L, Salvaggio MR, Sanchez WC, Sanjana VM, Santiago S, Schmidt W, Schuitemaker H, Sestak PM, Shalit P, Shay W, Shirvani VN, Silebi VI, Sizemore JM Jr, Skolnik PR, Sokol-Anderson M, Sosman JM, Stabile P, Stapleton JT, Starrett S, Stein F, Stellbrink HJ, Sterman FL, Stone VE, Stone DR, Tambussi G, Taplitz RA, Tedaldi EM, Telenti A, Theisen W, Torres R, Tosiello L, Tremblay C, Tribble MA, Trinh PD, Tsao A, Ueda P, Vaccaro A, Valadas E, Vanig TJ, Vecino I, Vega VM, Veikley W, Wade BH, Walworth C, Wanidworanun C, Ward DJ, Warner DA, Weber RD, Webster D, Weis S, Wheeler DA, White DJ, Wilkins E, Winston A, Wlodaver CG, van't Wout A, Wright DP, Yang OO, Yurdin DL, Zabukovic BW, Zachary KC, Zeeman B, and Zhao M

Subjects
Black or African American genetics, Alleles, Amino Acids physiology, CD8-Positive T-Lymphocytes immunology, Cohort Studies, Disease Progression, Genome-Wide Association Study, HIV Antigens immunology, HIV Infections ethnology, HIV Infections virology, HIV Long-Term Survivors, HLA-A Antigens chemistry, HLA-A Antigens genetics, HLA-A Antigens immunology, HLA-A Antigens metabolism, HLA-B Antigens chemistry, HLA-B Antigens immunology, HLA-B Antigens metabolism, HLA-C Antigens chemistry, HLA-C Antigens genetics, HLA-C Antigens immunology, HLA-C Antigens metabolism, Haplotypes, Hispanic or Latino genetics, Humans, Immunity, Innate, Logistic Models, Models, Molecular, Polymorphism, Single Nucleotide, Protein Conformation, Viral Load, White People genetics, Antigen Presentation, Genes, MHC Class I, HIV Infections genetics, HIV Infections immunology, HIV-1 immunology, HLA-B Antigens genetics
Abstract

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection.

Published
2010
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2. Long-term persistence of primary genotypic resistance after HIV-1 seroconversion.

Author

Pao D, Andrady U, Clarke J, Dean G, Drake S, Fisher M, Green T, Kumar S, Murphy M, Tang A, Taylor S, White D, Underhill G, Pillay D, and Cane P

Subjects
Genotype, HIV Infections drug therapy, HIV Infections virology, HIV Protease genetics, HIV Reverse Transcriptase genetics, HIV Seropositivity, Humans, Mutation, Time Factors, Anti-HIV Agents pharmacology, Drug Resistance, Viral genetics, HIV Protease Inhibitors pharmacology, HIV-1 drug effects, Reverse Transcriptase Inhibitors pharmacology
Abstract

Primary infection with drug-resistant HIV-1 is well documented. We have followed up patients infected with such viruses to determine the stability of resistance-associated mutations. Fourteen patients who experienced primary infection with genotypic evidence of resistance were followed for up to 3 years. Drug resistance-associated mutations persisted over time in most patients studied. In particular, M41L, T69N, K103N, and T215 variants within reverse transcriptase (RT) and multidrug resistance demonstrated little reversion to wild-type virus. By contrast, Y181C and K219Q in RT, occurring alone, disappeared within 25 and 9 months, respectively. Multidrug resistance in 2 patients was found to be stable for up to 18 months, the maximum period studied. We conclude that certain resistance-associated mutations are highly stable and these data support the recommendation that all new HIV diagnoses in areas where primary resistance may occur should undergo genotyping irrespective of whether the date of seroconversion is known.

Published
2004
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3. A highly virulent variant of HIV-1 circulating in the Netherlands

Author

Wymant, Chris, Bezemer, Daniela, Blanquart, François, Ferretti, Luca, Gall, Astrid, Hall, Matthew, Golubchik, Tanya, Bakker, Margreet, Ong, Swee Hoe, Zhao, Lele, Bonsall, David, de Cesare, Mariateresa, MacIntyre-Cockett, George, Abeler-Dörner, Lucie, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Grabowski, M Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F, Kivelä, Pia, Kouyos, Roger D, Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, Ristola, Matti, van Sighem, Ard, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, Aubert, V, Battegay, M, Bernasconi, E, Böni, J, Braun, D L, Bucher, H C, Burton-Jeangros, C, Calmy, A, Cavassini, M, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Furrer, H, Fux, C A, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, H H, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B Martinez, Marzolini, C, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni-Affolter, F, Schmid, P, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Weber, R, Yerly, S, van der Valk, M, Geerlings, S E, Goorhuis, A, Hovius, J W, Lempkes, B, Nellen, F J B, van der Poll, T, Prins, J M, Reiss, P, van Vugt, M, Wiersinga, W J, Wit, F W M N, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A M H, Pijnappel, F J J, Smalhout, S Y, Weijsenfeld, A M, Jurriaans, S, Back, N K T, Zaaijer, H L, Berkhout, B, Cornelissen, M T E, Schinkel, C J, Wolthers, K C, Peters, E J G, van Agtmael, M A, Autar, R S, Bomers, M, Sigaloff, K C E, Heitmuller, M, Laan, L M, Ang, C W, van Houdt, R, Jonges, M, Kuijpers, T W, Pajkrt, D, Scherpbier, H J, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Buiting, A, Reuwer, A, Veenemans, J, Wintermans, B, Pronk, M J H, Ammerlaan, H S M, van den Bersselaar, D N J, de Munnik, E S, Deiman, B, Jansz, A R, Scharnhorst, V, Tjhie, J, Wegdam, M C A, van Eeden, A, Nellen, J, Brokking, W, Elsenburg, L J M, Nobel, H, van Kasteren, M E E, Berrevoets, M A H, Brouwer, A E, Adams, A, van Erve, R, de Kruijf-van de Wiel, B A F M, Keelan-Phaf, S, van der Ven, B, Buiting, A G M, Murck, J L, de Vries-Sluijs, T E M S, Bax, H I, van Gorp, E C M, de Jong-Peltenburg, N C, de Mendonç A Melo, M, van Nood, E, Nouwen, J L, Rijnders, B J A, Rokx, C, Schurink, C A M, Slobbe, L, Verbon, A, Bassant, N, van Beek, J E A, Vriesde, M, van Zonneveld, L M, de Groot, J, Boucher, C A B, Koopmans, M P G, van Kampen, J J A, Fraaij, P L A, van Rossum, A M C, Vermont, C L, van der Knaap, L C, Visser, E, Branger, J, Douma, R A, Cents-Bosma, A S, Duijf-van de Ven, C J H M, Schippers, E F, van Nieuwkoop, C, van Ijperen, J M, Geilings, J, van der Hut, G, van Burgel, N D, Leyten, E M S, Gelinck, L B S, Mollema, F, Davids-Veldhuis, S, Tearno, C, Wildenbeest, G S, Heikens, E, Groeneveld, P H P, Bouwhuis, J W, Lammers, A J J, Kraan, S, van Hulzen, A G W, Kruiper, M S M, van der Bliek, G L, Bor, P C J, Debast, S B, Wagenvoort, G H J, Kroon, F P, de Boer, M G J, Jolink, H, Lambregts, M M C, Roukens, A H E, Scheper, H, Dorama, W, van Holten, N, Claas, E C J, Wessels, E, den Hollander, J G, El Moussaoui, R, Pogany, K, Smit, J V, Struik-Kalkman, D, van Niekerk, T, Pontesilli, O, Lowe, S H, Oude Lashof, A M L, Posthouwer, D, van Wolfswinkel, M E, Ackens, R P, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I H M, Havenith, T R A, van Vonderen, M G A, Kampschreur, L M, Faber, S, Steeman-Bouma, R, Al Moujahid, A, Kootstra, G J, Delsing, C E, van der Burg-van de Plas, M, Scheiberlich, L, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F A, Cohen Stuart, J W T, Jansen, E R, Hoogewerf, M, Rozemeijer, W, van der Reijden, W A, Sinnige, J C, Brinkman, K, van den Berk, G E L, Blok, W L, Lettinga, K D, de Regt, M, Schouten, W E M, Stalenhoef, J E, Veenstra, J, Vrouenraets, S M E, Blaauw, H, Geerders, G F, Kleene, M J, Kok, M, Knapen, M, van der Meché, I B, Mulder-Seeleman, E, Toonen, A J M, Wijnands, S, Wttewaal, E, Kwa, D, van Crevel, R, van Aerde, K, Dofferhoff, A S M, Henriet, S S V, Ter Hofstede, H J M, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K J T, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F F, Burger, D, Gisolf, E H, Hassing, R J, Claassen, M, Ter Beest, G, van Bentum, P H M, Langebeek, N, Tiemessen, R, Swanink, C M A, van Lelyveld, S F L, Soetekouw, R, van der Prijt, L M M, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B L, Veenendaal, D, Verhagen, D W M, Lauw, F N, van Broekhuizen, M C, van Wijk, M, Bierman, W F W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Postma, D F, Schölvinck, E H, Stienstra, Y, Verhage, A R, Wouthuyzen-Bakker, M, Boonstra, A, de Groot-de Jonge, H, van der Meulen, P A, de Weerd, D A, Niesters, H G M, van Leer-Buter, C C, Knoester, M, Hoepelman, A I M, Arends, J E, Barth, R E, Bruns, A H W, Ellerbroek, P M, Mudrikova, T, Oosterheert, J J, Schadd, E M, van Welzen, B J, Aarsman, K, Griffioen-van Santen, B M G, de Kroon, I, van Berkel, M, van Rooijen, C S A M, Schuurman, R, Verduyn-Lunel, F, Wensing, A M J, Bont, L J, Geelen, S P M, Loeffen, Y G T, Wolfs, T F W, Nauta, N, Rooijakkers, E O W, Holtsema, H, Voigt, R, van de Wetering, D, Alberto, A, van der Meer, I, Rosingh, A, Halaby, T, Zaheri, S, Boyd, A C, Bezemer, D O, van Sighem, A I, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Brétin, N, Djoechro, E, Groters, M, Kruijne, E, Lelivelt, K J, Lodewijk, C, Lucas, E, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnörr, P, Scheigrond, A, Tuijn, E, Veenenberg, L, Visser, K M, Witte, E C, Van Frankenhuijsen, Maartje, Allegre, Thierry, Makhloufi, Djamila, Livrozet, Jean-Michel, Chiarello, Pierre, Godinot, Mathieu, Brunel-Dalmas, Florence, Gibert, Sylvie, Trepo, Christian, Peyramond, Dominique, Miailhes, Patrick, Koffi, Joseph, Thoirain, Valérie, Brochier, Corinne, Baudry, Thomas, Pailhes, Sylvie, Lafeuillade, Alain, Philip, Gisèle, Hittinger, Gilles, Assi, Assi, Lambry, Véronique, Rosenthal, Eric, Naqvi, Alissa, Dunais, Brigitte, Cua, Eric, Pradier, Christian, Durant, Jacques, Joulie, Aline, Quinsat, Denis, Tempesta, Serge, Ravaux, Isabelle, Martin, Isabelle Poizot, Faucher, Olivia, Cloarec, Nicolas, Champagne, Hélène, Pichancourt, Gilles, Morlat, Philippe, Pistone, Thierry, Bonnet, Fabrice, Mercie, Patrick, Faure, Isabelle, Hessamfar, Mojgan, Malvy, Denis, Lacoste, Denis, Pertusa, Marie-Carmen, Vandenhende, Marie-Anne, Bernard, Noëlle, Paccalin, François, Martell, Cédric, Roger-Schmelz, Julien, Receveur, Marie-Catherine, Duffau, Pierre, Dondia, Denis, Ribeiro, Emmanuel, Caltado, Sabrina, Neau, Didier, Dupont, Michel, Dutronc, Hervé, Dauchy, Frédéric, Cazanave, Charles, Vareil, Marc-Olivier, Wirth, Gaétane, Le Puil, Séverine, Pellegrin, Jean-Luc, Raymond, Isabelle, Viallard, Jean-François, Chaigne de Lalande, Severin, Garipuy, Daniel, Delobel, Pierre, Obadia, Martine, Cuzin, Lise, Alvarez, Muriel, Biezunski, Noemie, Porte, Lydie, Massip, Patrice, Debard, Alexa, Balsarin, Florence, Lagarrigue, Myriam, Prevoteau du Clary, François, Aquilina, Christian, Reynes, Jacques, Baillat, Vincent, Merle, Corinne, Lemoing, Vincent, Atoui, Nadine, Makinson, Alain, Jacquet, Jean Marc, Psomas, Christina, Tramoni, Christine, Aumaitre, Hugues, Saada, Mathieu, Medus, Marie, Malet, Martine, Eden, Aurélia, Neuville, Ségolène, Ferreyra, Milagros, Sotto, Albert, Barbuat, Claudine, Rouanet, Isabelle, Leureillard, Didier, Mauboussin, Jean-Marc, Lechiche, Catherine, Donsesco, Régine, Cabie, André, Abel, Sylvie, Pierre-Francois, Sandrine, Batala, Anne-Sophie, Cerland, Christophe, Rangom, Camille, Theresine, Nadine, Hoen, Bruno, Lamaury, Isabelle, Fabre, Isabelle, Schepers, Kinda, Curlier, Elodie, Ouissa, Rachida, Gaud, Catherine, Ricaud, Carole, Rodet, Roland, Wartel, Guillaume, Sautron, Carmele, Beck-Wirth, Geneviève, Michel, Catherine, Beck, Charles, Halna, Jean-Michel, Kowalczyk, Jakub, Benomar, Meryem, Drobacheff-Thiebaut, Christine, Chirouze, Catherine, Faucher, Jean-François, Parcelier, François, Foltzer, Adeline, Haffner-Mauvais, Cécile, Hustache Mathieu, Mathieu, Proust, Aurélie, Piroth, Lionel, Chavanet, Pascal, Duong, Michel, Buisson, Marielle, Waldner, Anne, Mahy, Sophie, Gohier, Sandrine, Croisier, Delphine, May, Thierry, Delestan, Mikael, Andre, Marie, Zadeh, Mahsa Mohseni, Martinot, Martin, Rosolen, Béatrice, Pachart, Anne, Martha, Benoît, Jeunet, Noëlle, Rey, David, Cheneau, Christine, Partisani, Maria, Priester, Michèle, Bernard-Henry, Claudine, Batard, Marie-Laure, Fischer, Patricia, Berger, Jean-Luc, Kmiec, Isabelle, Robineau, Olivier, Huleux, Thomas, Ajana, Faïza, Alcaraz, Isabelle, Allienne, Christophe, Baclet, Véronique, Meybeck, Agnès, Valette, Michel, Viget, Nathalie, Aissi, Emmanuelle, Biekre, Raphael, Cornavin, Pauline, Merrien, Dominique, Seghezzi, Jean-Christophe, Machado, Moise, Diab, Georges, Raffi, François, Bonnet, Bénédicte, Allavena, Clotilde, Grossi, Olivier, Reliquet, Véronique, Billaud, Eric, Brunet, Cecile, Bouchez, Sabelline, Morineau-Le Houssine, Pascale, Sauser, Fabienne, Boutoille, David, Besnier, Michel, Hue, Hervé, Hall, Nolwenn, Brosseau, Delphine, Souala, Faouzi, Michelet, Christian, Tattevin, Pierre, Arvieux, Cédric, Revest, Matthieu, Leroy, Helene, Chapplain, Jean-Marc, Dupont, Matthieu, Fily, Fabien, Patra-Delo, Solène, Lefeuvre, Céline, Bernard, Louis, Bastides, Frédéric, Nau, Pascale, Verdon, Renaud, de la Blanchardiere, Arnaud, Martin, Anne, Feret, Philippe, Geffray, Loïk, Daniel, Corinne, Rohan, Jennifer, Fialaire, Pascale, Chennebault, Jean Marie, Rabier, Valérie, Abgueguen, Pierre, Rehaiem, Sami, Luycx, Odile, Niault, Mathilde, Moreau, Philippe, Poinsignon, Yves, Goussef, Marie, Mouton-Rioux, Virginie, Houlbert, Dominique, Alvarez-Huve, Sandrine, Barbe, Frédérique, Haret, Sophie, Perre, Philippe, Leantez-Nainville, Sophie, Esnault, Jean-Luc, Guimard, Thomas, Suaud, Isabelle, Girard, Jean-Jacques, Simonet, Véronique, Debab, Yasmine, Schmit, Jean-Luc, Jacomet, Christine, Weinberck, Pierre, Genet, Claire, Pinet, Pauline, Ducroix, Sophie, Durox, Hélène, Denes, Éric, Abraham, Bruno, Gourdon, Florence, Antoniotti, Odile, Molina, Jean-Michel, Ferret, Samuel, Lascoux-Combe, Caroline, Lafaurie, Matthieu, Colin de Verdiere, Nathalie, Ponscarme, Diane, De Castro, Nathalie, Aslan, Alexandre, Rozenbaum, Willy, Pintado, Claire, Clavel, François, Taulera, Olivier, Gatey, Caroline, Munier, Anne-Lise, Gazaigne, Sandrine, Penot, Pauline, Conort, Guillaume, Lerolle, Nathalie, Leplatois, Anne, Balausine, Stéphanie, Delgado, Jeannine, Timsit, Julie, Tabet, Magda, Gerard, Laurence, Girard, Pierre-Marie, Picard, Odile, Tredup, Jürgen, Bollens, Diane, Valin, Nadia, Campa, Pauline, Bottero, Julie, Lefebvre, Benedicte, Tourneur, Muriel, Fonquernie, Laurent, Wemmert, Charlotte, Lagneau, Jean-Luc, Yazdanpanah, Yazdan, Phung, Bao, Pinto, Adriana, Vallois, Dorothée, Cabras, Ornella, Louni, Françoise, Pialoux, Gilles, Lyavanc, Thomas, Berrebi, Valérie, Chas, Julie, Lenagat, Sophie, Rami, Agathe, Diemer, Myriam, Parrinello, Maguy, Depond, Audrey, Salmon, Dominique, Guillevin, Loïc, Tahi, Tassadit, Belarbi, Linda, Loulergue, Pierre, Zak Dit Zbar, Olivier, Launay, Odile, Silbermann, Benjamin, Leport, Catherine, Alagna, Laura, Pietri, Marie-Pierre, Simon, Anne, Bonmarchand, Manuela, Amirat, Naouel, Pichon, François, Kirstetter, Myriam, Katlama, Christine, Valantin, Marc Antoine, Tubiana, Roland, Caby, Fabienne, Schneider, Luminita, Ktorza, Nadine, Calin, Ruxandra, Merlet, Audrey, Ben Abdallah, Saadia, Weiss, Laurence, Buisson, Martin, Batisse, Dominique, Karmochine, Marina, Pavie, Juliette, Minozzi, Catherine, Jayle, Didier, Castel, Philippe, Derouineau, Jean, Kousignan, Pascale, Eliazevitch, Murielle, Pierre, Isabelle, Collias, Lio, Viard, Jean-Paul, Gilquin, Jacques, Sobel, Alain, Slama, Laurence, Ghosn, Jade, Hadacek, Blanka, Thu-Huyn, Nugyen, Nait-Ighil, Lella, Cros, Agnes, Maignan, Aline, Duvivier, Claudine, Consigny, Paul Henri, Lanternier, Fanny, Shoai-Tehrani, Michka, Touam, Fatima, Jerbi, Saadia, Bodard, Loïc, Jung, Corinne, Goujard, Cécile, Quertainmont, Yann, Duracinsky, Martin, Segeral, Olivier, Blanc, Arnaud, Peretti, Delphine, Cheret, Antoine, Chantalat, Christelle, Dulucq, Marie Josée, Levy, Yves, Lelievre, Jean Daniel, Lascaux, Anne Sophie, Dumont, Cécile, Boue, François, Chambrin, Véronique, Abgrall, Sophie, Kansau, Imad, Raho-Moussa, Mariem, De Truchis, Pierre, Dinh, Aurélien, Davido, Benjamin, Marigot, Dhiba, Berthe, Huguette, Devidas, Alain, Chevojon, Pierre, Chabrol, Amélie, Agher, Nouara, Lemercier, Yvon, Chaix, Fabrice, Turpault, Isabelle, Bouchaud, Olivier, Honore, Patricia, Rouveix, Elisabeth, Reimann, Evelyne, Belan, Alix Greder, Godin Collet, Claire, Souak, Safia, Mortier, Emmanuel, Bloch, Martine, Simonpoli, Anne-Marie, Manceron, Véronique, Cahitte, Isabelle, Hiraux, Emmanuel, Lafon, Erik, Cordonnier, François, Zeng, Ai-Feng, Zucman, David, Majerholc, Catherine, Bornarel, Dominique, Uludag, Agnès, Gellen-Dautremer, Justine, Lefort, Agnès, Bazin, Christine, Daneluzzi, Vincent, Gerbe, Juliette, Jeantils, Vincent, Coupard, Mélissa, Patey, Olivier, Bantsimba, Jonas, Delllion, Sophie, Paz, Pauline Caraux, Cazenave, Benoit, Richier, Laurent, Garrait, Valérie, Delacroix, Isabelle, Elharrar, Brigitte, Vittecoq, Daniel, Bolliot, Claudine, Lepretre, Annie, Genet, Philippe, Masse, Virginie, Perrone, Véronique, Boussard, Jean-Luc, Chardon, Patricia, Froguel, Eric, Simon, Philippe, Tassi, Sylvie, Avettand Fenoel, Véronique, Barin, Francis, Bourgeois, Christine, Cardon, Fanny, Chaix, Marie-Laure, Delfraissy, Jean François, Essat, Asma, Fischer, Hugues, Lecuroux, Camille, Petrov-Sanchez, Ventzislava, Rouzioux, Christine, Saez-Cirion, Asier, Seng, Rémonie, Kuldanek, Kristin, Mullaney, Scott, Young, Carmel, Zucchetti, Antonella, Bevan, Margaret-Ann, McKernan, Sinead, Wandolo, Emily, Richardson, Celia, Youssef, Elaney, Green, Pippa, Faulkner, Sue, Faville, Rebecca, Herman, Sandra, Care, Christine, Blackman, Helen, Bellenger, Katharine, Fairbrother, Keith, Phillips, Andrew, Babiker, Abdel, Delpech, Valerie, Fidler, S, Clarke, Mindy, Fox, Julie, Gilson, R, Goldberg, David, Hawkins, David, Johnson, Anne, Johnson, Margaret, McLean, Ken, Nastouli, Eleni, Post, Frank, Kennedy, N, Pritchard, J, Andrady, U, Rajda, N, Donnelly, C, McKernan, S, Drake, S, Gilleran, G, White, D, Ross, J, Harding, J, Faville, R, Sweeney, J, Flegg, P, Toomer, S, Wilding, H, Woodward, R, Dean, G, Richardson, C, Perry, N, Gompels, M, Jennings, L, Bansaal, D, Browing, M, Connolly, L, Stanley, B, Estreich, S, Magdy, A, O'Mahony, C, Fraser, P, Jebakumar, S P R, David, L, Mette, R, Summerfield, H, Evans, M, White, C, Robertson, R, Lean, C, Morris, S, Winter, A, Faulkner, S, Goorney, B, Howard, L, Fairley, I, Stemp, C, Short, L, Gomez, M, Young, F, Roberts, M, Green, S, Sivakumar, K, Minton, J, Siminoni, A, Calderwood, J, Greenhough, D, DeSouza, C, Muthern, Lisa, Orkin, C, Murphy, S, Truvedi, M, McLean, K, Hawkins, D, Higgs, C, Moyes, A, Antonucci, S, McCormack, S, Lynn, W, Bevan, M, Fox, J, Teague, A, Anderson, J, Mguni, S, Post, F, Campbell, L, Mazhude, C, Russell, H, Carrick, G, Ainsworth, J, Waters, A, Byrne, P, Johnson, M, Kuldanek, K, Mullaney, S, Lawlor, V, Melville, R, Sukthankar, A, Thorpe, S, Murphy, C, Wilkins, E, Ahmad, S, Green, P, Tayal, S, Ong, E, Meaden, J, Riddell, L, Loay, D, Peacock, K, Blackman, H, Harindra, V, Saeed, A M, Allen, S, Natarajan, U, Williams, O, Lacey, H, Care, C, Bowman, C, Herman, S, Devendra, S V, Wither, J, Bridgwood, A, Singh, G, Bushby, S, Kellock, D, Young, S, Rooney, G, Snart, B, Currie, J, Fitzgerald, M, Arumainayyagam, J, Chandramani, S, Rajamanoharan, S, Robinson, T, Taylor, B, Brewer, C, Mayr, Christoph, Schmidt, Wolfgang, Speidel, Andrea, Strohbach, Frank, Arastéh, Keikawus, Cordes, Christiane, Stündel, Manfred, Claus, Jörg, Baumgarten, Axel, Carganico, Andreas, Ingiliz, Patrick, Dupke, Stephan, Freiwald, Matthias, Rausch, Michael, Moll, Arend, Schleehauf, Dorothea, Hintsche, Bettina, Klausen, Gerd, Jessen, Heiko, Jessen, Arne, Köppe, Siegfried, Kreckel, Peter, Schranz, Dietmar, Fischer, Klaus, Schulbin, Hubert, Speer, Miriam, Glaunsinger, Tobias, Wicke, Thomas, Bieniek, Bernhard, Hillenbrand, Heribert, Schlote, Frank, Lauenroth-Mai, Elke, Schuler, Christoph, Schürmann, Dirk, Wesselmann, Hans, Brockmeyer, Norbert, Gehring, Peter, Schmalöer, Dirk, Hower, Martin, Spornraft-Ragaller, Petra, Häussinger, Dieter, Reuter, Stefan, Esser, Stefan, Markus, Rudolf, Kreft, Burkhard, Berzow, Dirk, Christl, Andreas, Meyer, Andreas, Plettenberg, Andreas, Stoehr, Albrecht, Graefe, Katrin, Lorenzen, Thore, Adam, Axel, Schewe, Knut, Weitner, Lutwin, Fenske, Stefan, Hansen, Stefan, Stellbrink, Hans-Jürgen, Wiemer, Dorothea, Hertling, Sandra, Schmidt, Reinhold, Arbter, Peter, Claus, Bernd, Galle, Peter, Jäger, Hans, Jä Gel-Guedes, Eva, Postel, Nils, Fröschl, Monika, Spinner, Christoph, Bogner, Johannes, Salzberger, Bernd, Schölmerich, Jürgen, Audebert, Franz, Marquardt, Ties, Schaffert, Andreas, Schnaitmann, Eiko, Trein, Andreas, Frietsch, Bernhard, Müller, Marcus, Ulmer, Albrecht, Detering-Hübner, Barbara, Kern, Peter, Schubert, Franz, Dehn, Günther, Schreiber, Maria, Güler, Cengiz, Schmidt, Daniel, Meixenberger, Karolin, Medical Microbiology & Infectious Diseases, Internal Medicine, Virology, Pediatrics, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Global Health, Infectious diseases, APH - Aging & Later Life, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Internal medicine, VU University medical center, Surgery, AMS - Rehabilitation & Development, APH - Quality of Care, Psychiatry, Pediatric surgery, Neurology, Public and occupational health, APH - Mental Health, Pathology, Cardiology, ACS - Heart failure & arrhythmias, Anesthesiology, IOO, Rehabilitation medicine, Obstetrics and gynaecology, General practice, Gastroenterology and hepatology, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Medical oncology laboratory, Hematology, Epidemiology and Data Science, Physiology, Microbes in Health and Disease (MHD), University of Oxford, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Amsterdam UMC - Amsterdam University Medical Center, The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Johns Hopkins University (JHU), Universität Zürich [Zürich] = University of Zurich (UZH), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, University College of London [London] (UCL), Kymab Ltd, Cambridge, England, Institut Pasteur [Paris] (IP), This study was funded by ERC Advanced Grant PBDR-339251 and a Li Ka Shing Foundation grant, both awarded to C.F. The ATHENA Cohort is managed by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment., We thank K. Fransen and G. Vanham for help with the Belgian data, O. Ratmann for help in identifying the Dutch clusters, K. Kusejko for testing for additional VB individuals in the SHCS, B. Foley for help with genome sharing, B. Dearlove and L. Thomson for help with software, and J. Herbeck and three other reviewers for helpful suggestions., Contributors and affiliations are listed in the supplementary materials., Department of Medicine, University of Helsinki, Infektiosairauksien yksikkö, HUS Inflammation Center, and Clinicum

Subjects
Adult, Male, HIV-1/genetics, Genotype, Anti-HIV Agents, Evolution, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections/drug therapy, selection, HIV Infections, Genome, Viral, heritability, epidemic, human-immunodeficiency-virus, Evolution, Molecular, SDG 3 - Good Health and Well-being, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Viral, Phylogeny, Netherlands, Multidisciplinary, Genome, model, Virulence, transmission, Molecular, setpoint viral load, reverse-transcriptase, dynamics, Viral Load, CD4 Lymphocyte Count, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 3121 General medicine, internal medicine and other clinical medicine, Anti-HIV Agents/therapeutic use, Mutation, HIV-1, Female, progression
Abstract

Comment in Does HIV-1 virulence matter in the ART era? Lewitus E, Rolland M. Med (N Y). 2022 Apr 8;3(4):217-219. doi: 10.1016/j.medj.2022.03.003. PMID: 35590149; International audience; We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

Published
2022
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