Search

Your search keyword '"Brumme, Z"' showing total 48 results
Start Over Author "Brumme, Z"
48 results on '"Brumme, Z"'

1. PP 3.6 – 00122 Heterogeneous associations between HIV genomic integrity and proviral longevity during long-term ART

Author

Brumme, Z., primary, Kinloch, N., additional, Shahid, A., additional, Dong, W., additional, Kirkby, D., additional, Jones, B.R., additional, Beelen, C., additional, MacMillan, D., additional, Mota, T.M., additional, Sudderuddin, H., additional, Barad, E., additional, Harris, M., additional, Brumme, C.J., additional, Jones, R. Brad, additional, Brockman, M.A., additional, and Joy, J.B., additional

Published
2022
Full Text
View/download PDF

10. Variable impact on mortality of AIDS-defining events diagnosed during combination antiretroviral therapy : not all AIDS-defining conditions are created equal

Author

Antiretroviral Therapy Cohort Collaboration Mocroft A, Sterne JA, Egger M, May M, Grabar S, Furrer H, Sabin C, Fatkenheuer G, Justice A, Reiss P, d'Arminio Monforte A, Gill J, Hogg R, Bonnet F, Kitahata M, Staszewski S, Casabona J, Harris R, Saag M, Chêne G, Costagliola D, Dabis F, D'Arminio Monforte A, de Wolf F, Ledergerber B, Mocroft A, Phillips A, Weller I, Sterne J, Abgrall S, Barin F, Bentata M, Billaud E, Boué F, Burty C, Cabié A, Cotte L, De Truchis P, Duval X, Duvivier C, Enel P, Fredouille Heripret L, Gasnault J, Gaud C, Gilquin J, Katlama C, Khuong MA, Lang JM, Lascaux AS, Launay O, Mahamat A, Mary Krause M, Matheron S, Meynard JL, Pavie J, Pialoux G, Pilorgé F, Poizot Martin I, Pradier C, Reynes J, Rouveix E, Simon A, Tattevin P, Tissot Dupont H, Viard JP, Viget N, Pariente Khayat A, Salomon V, Jacquemet N, Rivet A, Guiguet M, Kousignian I, Lanoy E, Lièvre L, Potard V, Selinger Leneman H, Bouvet E, Crickx B, Ecobichon JL, Leport C, Picard Dahan C, Yeni P, Tisne Dessus D, Weiss L, Salmon D, Sicard D, Auperin I, Roudière L, Fior R, Delfraissy JF, Goujard C, Jung C, Lesprit P, Desplanque N, Meyohas MC, Picard O, Cadranel J, Mayaud C, Bricaire F, Herson S, Clauvel JP, Decazes JM, Gerard L, Molina JM, Diemer M, Sellier P, Berthé H, Dupont C, Chandemerle C, Mortier E, Honoré P, Jeantils V, Tassi S, Mechali D, Taverne B, Gourdon F, Laurichesse H, Fresard A, Lucht F, Eglinger P, Faller JP, Bazin C, Verdon R, Boibieux A, Peyramond D, Livrozet JM, Touraine JL, Trepo C, Ravaux I, Delmont JP, Moreau J, Gastaut JA, Retornaz F, Soubeyrand J, Allegre T, Blanc PA, Galinier A, Ruiz JM, Lepeu G, Granet Brunello P, Esterni JP, Pelissier L, Cohen Valensi R, Nezri M, Chadapaud S, Laffeuillade A, May T, Rabaud C, Raffi F, Arvieux C, Michelet C, Borsa Lebas F, Caron F, Fraisse P, Rey D, Arlet Suau E, Cuzin L, Massip P, Thiercelin Legrand MF, Yasdanpanah Y, Pradinaud R, Sobesky M, Contant M, Montroni M, Scalise G, Braschi MC, Riva A, Tirelli U, Martellotta F, Pastore G, Ladisa N, Suter F, Arici C, Chiodo F, Colangeli V, Fiorini C, Carosi G, Cristini G, Torti C, Minardi C, Bertelli D, Quirino T, Manconi PE, Piano P, Cosco L, Scerbo A, Vecchiet J, D'Alessandro M, Santoro D, Pusterla L, Carnevale G, Lorenzotti S, Viganò P, Mena M, Ghinelli F, Sighinolfi L, Leoncini F, Mazzotta F, Pozzi M, Lo Caputo S, Grisorio B, Ferrara S, Grima P, Grima PF, Pagano G, Cassola G, Alessandrini A, Piscopo R, Toti M, Trezzi M, Soscia F, Tacconi L, Orani A, Perini P, Scasso A, Vincenti A, Chiodera F, Castelli P, Scalzini A, Palvarini L, Moroni M, Lazzarin A, Rizzardini G, Caggese L, Cicconi P, Galli A, Merli S, Pastecchia C, Moioli MC, Esposito R, Mussini C, Abrescia N, Chirianni A, Izzo CM, Piazza M, De Marco M, Viglietti R, Manzillo E, Colomba A, Abbadessa V, Prestileo T, Mancuso S, Ferrari C, Pizzaferri P, Filice G, Minoli L, Bruno R, Novati S, Baldelli F, Camanni G, Petrelli E, Cioppi A, Alberici F, Ruggieri A, Menichetti F, Martinelli C, De Stefano C, La Gala A, Ballardini G, Rizzo E, Magnani G, Ursitti MA, Arlotti M, Ortolani P, Cauda R, Dianzani F, Ippolito G, Antinori A, Antonucci G, Ciardi M, Narciso P, Petrosillo N, Vullo V, De Luca A, Zaccarelli M, Acinapura R, De Longis P, Trotta MP, Noto P, Lichtner M, Capobianchi MR, Carletti F, Girardi E, Pezzotti P, Rezza G, Mura MS, Mannazzu M, Caramello P, Di Perri G, Orofino GC, Sciandra M, Grossi PA, Basilico C, Poggio A, Bottari G, Raise E, Ebo F, Pellizzer G, Buonfrate D, Resta F, Loso K, Cozzi Lepri A, Battegay M, Bernasconi E, Böni J, Bucher H, Bürgisser P, Cattacin S, Cavassini M, Dubs R, Elzi L, Erb P, Fischer M, Flepp M, Fontana A, Francioli P, Gorgievski M, Günthard H, Hirsch H, Hirschel B, Hösli I, Kahlert C, Kaiser L, Karrer U, Kind C, Klimkait T, Martinetti G, Martinez B, Müller N, Nadal D, Opravil M, Paccaud F, Pantaleo G, Rickenbach M, Rudin C, Schmid P, Schultze D, Schüpbach J, Speck R, Taffé P, Tarr P, Telenti A, Trkola A, Vernazza P, Weber R, Yerly S, Gras LA, van Sighem AI, Smit C, Bronsveld W, Hillebrand Haverkort ME, Prins JM, Branger J, Eeftinck Schattenkerk JK, Gisolf J, Godfried MH, Lange JM, Lettinga KD, van der Meer JT, Nellen FJ, van der Poll T, Ruys TA, Steingrover R, Vermeulen JN, Vrouenraets SM, van Vugt M, Wit FW, Kuijpers TW, Pajkrt D, Scherpbier HJ, van Eeden A, Brinkman K, van den Berk GE, Blok WL, Frissen PH, Roos JC, Schouten WE, Mulder JW, van Gorp EC, Wagenaar J, Veenstra J, Danner SA, Van Agtmael MA, Claessen FA, Perenboom RM, Rijkeboer A, van Vonderen MG, Richter C, van der Berg J, Vriesendorp R, Jeurissen FJ, Kauffmann RH, Pogány K, Bravenboer B, ten Napel CH, Kootstra GJ, Sprenger HG, van Assen S, van Leeuwen JT, Doedens R, Scholvinck EH, ten Kate RW, Soetekouw R, van Houte D, Polée MB, Kroon FP, van den Broek PJ, van Dissel JT, Schippers EF, Schreij G, van der Geest S, Lowe S, Verbon A, Koopmans PP, Van Crevel R, de Groot R, Keuter M, Post F, van der Ven AJ, Warris A, van der Ende ME, Gyssens IC, van der Feltz M, Nouwen JL, Rijnders BJ, de Vries TE, Driessen G, van der Flier M, Hartwig NG, Juttman JR, van Kasteren ME, Van de Heul C, Hoepelman IM, Schneider MM, Bonten MJ, Borleffs JC, Ellerbroek PM, Jaspers CA, Mudrikove T, Schurink CA, Gisolf EH, Geelen SP, Wolfs TF, Faber T, Tanis AA, Groeneveld PH, den Hollander JG, Duits AJ, Winkel K, Back NK, Bakker ME, Berkhout B, Jurriaans S, Zaaijer HL, Cuijpers T, Rietra PJ, Roozendaal KJ, Pauw W, van Zanten AP, Smits PH, von Blomberg BM, Savelkoul P, Pettersson A, Swanink CM, Franck PF, Lampe AS, Jansen CL, Hendriks R, Benne CA, Veenendaal D, Storm H, Weel J, van Zeijl JH, Kroes AC, Claas HC, Bruggeman CA, Goossens VJ, Galama JM, Melchers WJ, Poort YA, Doornum GJ, Niesters MG, Osterhaus AD, Schutten M, Buiting AG, Swaans CA, Boucher CA, Schuurman R, Boel E, Jansz AF, Veldkamp A, Beijnen JH, Huitema AD, Burger DM, Hugen PW, van Kan HJ, Losso M, Duran A, Vetter N, Karpov I, Vassilenko A, Mitsura VM, Suetnov O, Clumeck N, De Wit S, Poll B, Colebunders R, Kostov K, Begovac J, Machala L, Rozsypal H, Sedlacek D, Nielsen J, Lundgren J, Benfield T, Kirk O, Gerstoft J, Katzenstein T, Hansen AB, Skinhøj P, Pedersen C, Oestergaard L, Zilmer K, Ristola M, Girard PM, Vanhems P, Rockstroh J, Schmidt R, van Lunzen J, Degen O, Stellbrink HJ, Bogner J, Kosmidis J, Gargalianos P, Xylomenos G, Perdios J, Panos G, Filandras A, Karabatsaki E, Sambattakou H, Banhegyi D, Mulcahy F, Yust I, Turner D, Burke M, Pollack S, Hassoun G, Maayan S, Chiesi A, Mazeu I, Pristera R, Gabbuti A, Montesarchio E, Gargiulo M, Iacomi F, Vlassi C, Finazzi R, Galli M, Ridolfo A, Rozentale B, Aldins P, Chaplinskas S, Hemmer R, Staub T, Bruun J, Maeland A, Ormaasen V, Knysz B, Gasiorowski J, Horban A, Prokopowicz D, Wiercinska Drapalo A, Boron Kaczmarska A, Pynka M, Beniowski M, Mularska E, Trocha H, Antunes F, Valadas E, Mansinho K, Maltez F, Duiculescu D, Rakhmanova A, Vinogradova E, Buzunova S, Jevtovic D, Mokrás M, Staneková D, González Lahoz J, Soriano V, Martin Carbonero L, Labarga P, Clotet B, Jou A, Conejero J, Tural C, Gatell JM, Miró JM, Domingo P, Gutierrez M, Mateo G, Sambeat MA, Karlsson A, Persson PO, Flamholc L, Boffi E, Kravchenko E, Chentsova N, Barton S, Johnson AM, Mercey D, Johnson MA, Murphy M, Weber J, Scullard G, Fisher M, Brettle R, Gatell J, Gazzard B, Friis Møller N, Bannister W, Ellefson M, Borch A, Podlekareva D, Holkmann Olsen C, Kjaer J, Peters L, Reekie J, Raffanti S, Dieterch D, Becker S, Scarsella A, Fusco G, Most B, Balu R, Rana R, Beckerman R, Ising T, Fusco J, Irek R, Johnson B, Hirani A, DeJesus E, Pierone G, Lackey P, Irek C, Johnson A, Burdick J, Leon S, Arch J, Helm EB, Carlebach A, Müller A, Haberl A, Nisius G, Lennemann T, Stephan C, Bickel M, Mösch M, Gute P, Locher L, Lutz T, Klauke S, Knecht G, Khaykin P, Doerr HW, Stürmer M, Babacan E, von Hentig N, Beylot J, Dupon M, Longy Boursier M, Pellegrin JL, Ragnaud JM, Salamon R, Thiébaut R, Lewden C, Lawson Ayayi S, Mercié P, Moreau JF, Morlat P, Bernard N, Lacoste D, Malvy D, Neau D, Blaizeau MJ, Decoin M, Delveaux S, Hannapier C, Labarrère S, Lavignolle Aurillac V, Uwamaliya Nziyumvira B, Palmer G, Touchard D, Balestre E, Alioum A, Jacqmin Gadda H, Bonarek M, Coadou B, Gellie P, Nouts C, Bocquentin F, Dutronc H, Lafarie S, Aslan A, Pistonne T, Thibaut P, Vatan R, Chambon D, De La Taille C, Cazorla C, Ocho A, Viallard JF, Caubet O, Cipriano C, Lazaro E, Couzigou P, Castera L, Fleury H, Lafon ME, Masquelier B, Pellegrin I, Breilh D, Blanco P, Loste P, Caunègre L, Bonnal F, Farbos S, Ferrand M, Ceccaldi J, Tchamgoué S, De Witte S, Buy E, Alexander C, Barrios R, Braitstein P, Brumme Z, Chan K, Cote H, Gataric N, Geller J, Guillemi S, Harrigan PR, Harris M, Joy R, Levy A, Montaner J, Montessori V, Palepu A, Phillips E, Phillips P, Press N, Tyndall M, Wood E, Yip B, Bhagani S, Breen R, Byrne P, Carroll A, Cuthbertson Z, Dunleavy A, Geretti AM, Heelan B, Johnson M, Kinloch de Loes S, Lipman M, Madge S, Marshall N, Nair D, Nebbia G, Prinz B, Shah S, Swader L, Tyrer M, Youle M, Chaloner C, Grabowska H, Holloway J, Puradiredja J, Ransom D, Tsintas R, Bansi L, Fox Z, Harris E, Hill T, Lampe F, Lodwick R, Smith C, Amoah E, Booth C, Clewley G, Garcia Diaz A, Gregory B, Janossy G, Labbett W, Thomas M, Read R, Krentz H, Beckthold B, Schmeisser N, Alquézar A, Esteve A, Podzamczer D, Murillas J, Romero A, Agustí C, Agüero F, Ferrer E, Riera M, Segura F, Navarro G, Force L, Vilaró J, Masabeu A, García I, Guadarrama M, Montoliu A, Ortega N, Lazzari E, Puchol E, Sanchez M, Blanco JL, Garcia Alcaide F, Martinez E, Mallolas J, López Dieguez M, García Goez JF, Sirera G, Romeu J, Negredo E, Miranda C, Capitan MC, Olmo M, Barragan P, Saumoy M, Bolao F, Cabellos C, Peña C, Sala M, Cervantes M, Jose Amengual M, Navarro M, Penelo E, Barrufet P, Raper JL, Mugavero MJ, Willig JH, Schumacher J, Chang PW, Westfall AO, Cloud G, Lin HY, Acosta EP, Colette Kempf M, Allison JJ, Pisu M., NAPPA, SALVATORE, Mocroft, A, Mancuso, S, Antiretroviral Therapy Cohort Collaboration Mocroft, A, Sterne, Ja, Egger, M, May, M, Grabar, S, Furrer, H, Sabin, C, Fatkenheuer, G, Justice, A, Reiss, P, d'Arminio Monforte, A, Gill, J, Hogg, R, Bonnet, F, Kitahata, M, Staszewski, S, Casabona, J, Harris, R, Saag, M, Chêne, G, Costagliola, D, Dabis, F, D'Arminio Monforte, A, de Wolf, F, Ledergerber, B, Phillips, A, Weller, I, Sterne, J, Abgrall, S, Barin, F, Bentata, M, Billaud, E, Boué, F, Burty, C, Cabié, A, Cotte, L, De Truchis, P, Duval, X, Duvivier, C, Enel, P, Fredouille Heripret, L, Gasnault, J, Gaud, C, Gilquin, J, Katlama, C, Khuong, Ma, Lang, Jm, Lascaux, A, Launay, O, Mahamat, A, Mary Krause, M, Matheron, S, Meynard, Jl, Pavie, J, Pialoux, G, Pilorgé, F, Poizot Martin, I, Pradier, C, Reynes, J, Rouveix, E, Simon, A, Tattevin, P, Tissot Dupont, H, Viard, Jp, Viget, N, Pariente Khayat, A, Salomon, V, Jacquemet, N, Rivet, A, Guiguet, M, Kousignian, I, Lanoy, E, Lièvre, L, Potard, V, Selinger Leneman, H, Bouvet, E, Crickx, B, Ecobichon, Jl, Leport, C, Picard Dahan, C, Yeni, P, Tisne Dessus, D, Weiss, L, Salmon, D, Sicard, D, Auperin, I, Roudière, L, Fior, R, Delfraissy, Jf, Goujard, C, Jung, C, Lesprit, P, Desplanque, N, Meyohas, Mc, Picard, O, Cadranel, J, Mayaud, C, Bricaire, F, Herson, S, Clauvel, Jp, Decazes, Jm, Gerard, L, Molina, Jm, Diemer, M, Sellier, P, Berthé, H, Dupont, C, Chandemerle, C, Mortier, E, Honoré, P, Jeantils, V, Tassi, S, Mechali, D, Taverne, B, Gourdon, F, Laurichesse, H, Fresard, A, Lucht, F, Eglinger, P, Faller, Jp, Bazin, C, Verdon, R, Boibieux, A, Peyramond, D, Livrozet, Jm, Touraine, Jl, Trepo, C, Ravaux, I, Delmont, Jp, Moreau, J, Gastaut, Ja, Retornaz, F, Soubeyrand, J, Allegre, T, Blanc, Pa, Galinier, A, Ruiz, Jm, Lepeu, G, Granet Brunello, P, Esterni, Jp, Pelissier, L, Cohen Valensi, R, Nezri, M, Chadapaud, S, Laffeuillade, A, May, T, Rabaud, C, Raffi, F, Arvieux, C, Michelet, C, Borsa Lebas, F, Caron, F, Fraisse, P, Rey, D, Arlet Suau, E, Cuzin, L, Massip, P, Thiercelin Legrand, Mf, Yasdanpanah, Y, Pradinaud, R, Sobesky, M, Contant, M, Montroni, M, Scalise, G, Braschi, Mc, Riva, A, Tirelli, U, Martellotta, F, Pastore, G, Ladisa, N, Suter, F, Arici, C, Chiodo, F, Colangeli, V, Fiorini, C, Carosi, G, Cristini, G, Torti, C, Minardi, C, Bertelli, D, Quirino, T, Manconi, Pe, Piano, P, Cosco, L, Scerbo, A, Vecchiet, J, D'Alessandro, M, Santoro, D, Pusterla, L, Carnevale, G, Lorenzotti, S, Viganò, P, Mena, M, Ghinelli, F, Sighinolfi, L, Leoncini, F, Mazzotta, F, Pozzi, M, Lo Caputo, S, Grisorio, B, Ferrara, S, Grima, P, Grima, Pf, Pagano, G, Cassola, G, Alessandrini, A, Piscopo, R, Toti, M, Trezzi, M, Soscia, F, Tacconi, L, Orani, A, Perini, P, Scasso, A, Vincenti, A, Chiodera, F, Castelli, P, Scalzini, A, Palvarini, L, Moroni, M, Lazzarin, A, Rizzardini, G, Caggese, L, Cicconi, P, Galli, A, Merli, S, Pastecchia, C, Moioli, Mc, Esposito, R, Mussini, C, Abrescia, N, Chirianni, A, Izzo, Cm, Piazza, M, De Marco, M, Viglietti, R, Manzillo, E, Nappa, Salvatore, Colomba, A, Abbadessa, V, Prestileo, T, Ferrari, C, Pizzaferri, P, Filice, G, Minoli, L, Bruno, R, Novati, S, Baldelli, F, Camanni, G, Petrelli, E, Cioppi, A, Alberici, F, Ruggieri, A, Menichetti, F, Martinelli, C, De Stefano, C, La Gala, A, Ballardini, G, Rizzo, E, Magnani, G, Ursitti, Ma, Arlotti, M, Ortolani, P, Cauda, R, Dianzani, F, Ippolito, G, Antinori, A, Antonucci, G, Ciardi, M, Narciso, P, Petrosillo, N, Vullo, V, De Luca, A, Zaccarelli, M, Acinapura, R, De Longis, P, Trotta, Mp, Noto, P, Lichtner, M, Capobianchi, Mr, Carletti, F, Girardi, E, Pezzotti, P, Rezza, G, Mura, M, Mannazzu, M, Caramello, P, Di Perri, G, Orofino, Gc, Sciandra, M, Grossi, Pa, Basilico, C, Poggio, A, Bottari, G, Raise, E, Ebo, F, Pellizzer, G, Buonfrate, D, Resta, F, Loso, K, Cozzi Lepri, A, Battegay, M, Bernasconi, E, Böni, J, Bucher, H, Bürgisser, P, Cattacin, S, Cavassini, M, Dubs, R, Elzi, L, Erb, P, Fischer, M, Flepp, M, Fontana, A, Francioli, P, Gorgievski, M, Günthard, H, Hirsch, H, Hirschel, B, Hösli, I, Kahlert, C, Kaiser, L, Karrer, U, Kind, C, Klimkait, T, Martinetti, G, Martinez, B, Müller, N, Nadal, D, Opravil, M, Paccaud, F, Pantaleo, G, Rickenbach, M, Rudin, C, Schmid, P, Schultze, D, Schüpbach, J, Speck, R, Taffé, P, Tarr, P, Telenti, A, Trkola, A, Vernazza, P, Weber, R, Yerly, S, Gras, La, van Sighem, Ai, Smit, C, Bronsveld, W, Hillebrand Haverkort, Me, Prins, Jm, Branger, J, Eeftinck Schattenkerk, Jk, Gisolf, J, Godfried, Mh, Lange, Jm, Lettinga, Kd, van der Meer, Jt, Nellen, Fj, van der Poll, T, Ruys, Ta, Steingrover, R, Vermeulen, Jn, Vrouenraets, Sm, van Vugt, M, Wit, Fw, Kuijpers, Tw, Pajkrt, D, Scherpbier, Hj, van Eeden, A, Brinkman, K, van den Berk, Ge, Blok, Wl, Frissen, Ph, Roos, Jc, Schouten, We, Mulder, Jw, van Gorp, Ec, Wagenaar, J, Veenstra, J, Danner, Sa, Van Agtmael, Ma, Claessen, Fa, Perenboom, Rm, Rijkeboer, A, van Vonderen, Mg, Richter, C, van der Berg, J, Vriesendorp, R, Jeurissen, Fj, Kauffmann, Rh, Pogány, K, Bravenboer, B, ten Napel, Ch, Kootstra, Gj, Sprenger, Hg, van Assen, S, van Leeuwen, Jt, Doedens, R, Scholvinck, Eh, ten Kate, Rw, Soetekouw, R, van Houte, D, Polée, Mb, Kroon, Fp, van den Broek, Pj, van Dissel, Jt, Schippers, Ef, Schreij, G, van der Geest, S, Lowe, S, Verbon, A, Koopmans, Pp, Van Crevel, R, de Groot, R, Keuter, M, Post, F, van der Ven, Aj, Warris, A, van der Ende, Me, Gyssens, Ic, van der Feltz, M, Nouwen, Jl, Rijnders, Bj, de Vries, Te, Driessen, G, van der Flier, M, Hartwig, Ng, Juttman, Jr, van Kasteren, Me, Van de Heul, C, Hoepelman, Im, Schneider, Mm, Bonten, Mj, Borleffs, Jc, Ellerbroek, Pm, Jaspers, Ca, Mudrikove, T, Schurink, Ca, Gisolf, Eh, Geelen, Sp, Wolfs, Tf, Faber, T, Tanis, Aa, Groeneveld, Ph, den Hollander, Jg, Duits, Aj, Winkel, K, Back, Nk, Bakker, Me, Berkhout, B, Jurriaans, S, Zaaijer, Hl, Cuijpers, T, Rietra, Pj, Roozendaal, Kj, Pauw, W, van Zanten, Ap, Smits, Ph, von Blomberg, Bm, Savelkoul, P, Pettersson, A, Swanink, Cm, Franck, Pf, Lampe, A, Jansen, Cl, Hendriks, R, Benne, Ca, Veenendaal, D, Storm, H, Weel, J, van Zeijl, Jh, Kroes, Ac, Claas, Hc, Bruggeman, Ca, Goossens, Vj, Galama, Jm, Melchers, Wj, Poort, Ya, Doornum, Gj, Niesters, Mg, Osterhaus, Ad, Schutten, M, Buiting, Ag, Swaans, Ca, Boucher, Ca, Schuurman, R, Boel, E, Jansz, Af, Veldkamp, A, Beijnen, Jh, Huitema, Ad, Burger, Dm, Hugen, Pw, van Kan, Hj, Losso, M, Duran, A, Vetter, N, Karpov, I, Vassilenko, A, Mitsura, Vm, Suetnov, O, Clumeck, N, De Wit, S, Poll, B, Colebunders, R, Kostov, K, Begovac, J, Machala, L, Rozsypal, H, Sedlacek, D, Nielsen, J, Lundgren, J, Benfield, T, Kirk, O, Gerstoft, J, Katzenstein, T, Hansen, Ab, Skinhøj, P, Pedersen, C, Oestergaard, L, Zilmer, K, Ristola, M, Girard, Pm, Vanhems, P, Rockstroh, J, Schmidt, R, van Lunzen, J, Degen, O, Stellbrink, Hj, Bogner, J, Kosmidis, J, Gargalianos, P, Xylomenos, G, Perdios, J, Panos, G, Filandras, A, Karabatsaki, E, Sambattakou, H, Banhegyi, D, Mulcahy, F, Yust, I, Turner, D, Burke, M, Pollack, S, Hassoun, G, Maayan, S, Chiesi, A, Mazeu, I, Pristera, R, Gabbuti, A, Montesarchio, E, Gargiulo, M, Iacomi, F, Vlassi, C, Finazzi, R, Galli, M, Ridolfo, A, Rozentale, B, Aldins, P, Chaplinskas, S, Hemmer, R, Staub, T, Bruun, J, Maeland, A, Ormaasen, V, Knysz, B, Gasiorowski, J, Horban, A, Prokopowicz, D, Wiercinska Drapalo, A, Boron Kaczmarska, A, Pynka, M, Beniowski, M, Mularska, E, Trocha, H, Antunes, F, Valadas, E, Mansinho, K, Maltez, F, Duiculescu, D, Rakhmanova, A, Vinogradova, E, Buzunova, S, Jevtovic, D, Mokrás, M, Staneková, D, González Lahoz, J, Soriano, V, Martin Carbonero, L, Labarga, P, Clotet, B, Jou, A, Conejero, J, Tural, C, Gatell, Jm, Miró, Jm, Domingo, P, Gutierrez, M, Mateo, G, Sambeat, Ma, Karlsson, A, Persson, Po, Flamholc, L, Boffi, E, Kravchenko, E, Chentsova, N, Barton, S, Johnson, Am, Mercey, D, Johnson, Ma, Murphy, M, Weber, J, Scullard, G, Fisher, M, Brettle, R, Gatell, J, Gazzard, B, Friis Møller, N, Bannister, W, Ellefson, M, Borch, A, Podlekareva, D, Holkmann Olsen, C, Kjaer, J, Peters, L, Reekie, J, Raffanti, S, Dieterch, D, Becker, S, Scarsella, A, Fusco, G, Most, B, Balu, R, Rana, R, Beckerman, R, Ising, T, Fusco, J, Irek, R, Johnson, B, Hirani, A, Dejesus, E, Pierone, G, Lackey, P, Irek, C, Johnson, A, Burdick, J, Leon, S, Arch, J, Helm, Eb, Carlebach, A, Müller, A, Haberl, A, Nisius, G, Lennemann, T, Stephan, C, Bickel, M, Mösch, M, Gute, P, Locher, L, Lutz, T, Klauke, S, Knecht, G, Khaykin, P, Doerr, Hw, Stürmer, M, Babacan, E, von Hentig, N, Beylot, J, Dupon, M, Longy Boursier, M, Pellegrin, Jl, Ragnaud, Jm, Salamon, R, Thiébaut, R, Lewden, C, Lawson Ayayi, S, Mercié, P, Moreau, Jf, Morlat, P, Bernard, N, Lacoste, D, Malvy, D, Neau, D, Blaizeau, Mj, Decoin, M, Delveaux, S, Hannapier, C, Labarrère, S, Lavignolle Aurillac, V, Uwamaliya Nziyumvira, B, Palmer, G, Touchard, D, Balestre, E, Alioum, A, Jacqmin Gadda, H, Bonarek, M, Coadou, B, Gellie, P, Nouts, C, Bocquentin, F, Dutronc, H, Lafarie, S, Aslan, A, Pistonne, T, Thibaut, P, Vatan, R, Chambon, D, De La Taille, C, Cazorla, C, Ocho, A, Viallard, Jf, Caubet, O, Cipriano, C, Lazaro, E, Couzigou, P, Castera, L, Fleury, H, Lafon, Me, Masquelier, B, Pellegrin, I, Breilh, D, Blanco, P, Loste, P, Caunègre, L, Bonnal, F, Farbos, S, Ferrand, M, Ceccaldi, J, Tchamgoué, S, De Witte, S, Buy, E, Alexander, C, Barrios, R, Braitstein, P, Brumme, Z, Chan, K, Cote, H, Gataric, N, Geller, J, Guillemi, S, Harrigan, Pr, Harris, M, Joy, R, Levy, A, Montaner, J, Montessori, V, Palepu, A, Phillips, E, Phillips, P, Press, N, Tyndall, M, Wood, E, Yip, B, Bhagani, S, Breen, R, Byrne, P, Carroll, A, Cuthbertson, Z, Dunleavy, A, Geretti, Am, Heelan, B, Johnson, M, Kinloch de Loes, S, Lipman, M, Madge, S, Marshall, N, Nair, D, Nebbia, G, Prinz, B, Shah, S, Swader, L, Tyrer, M, Youle, M, Chaloner, C, Grabowska, H, Holloway, J, Puradiredja, J, Ransom, D, Tsintas, R, Bansi, L, Fox, Z, Harris, E, Hill, T, Lampe, F, Lodwick, R, Smith, C, Amoah, E, Booth, C, Clewley, G, Garcia Diaz, A, Gregory, B, Janossy, G, Labbett, W, Thomas, M, Read, R, Krentz, H, Beckthold, B, Schmeisser, N, Alquézar, A, Esteve, A, Podzamczer, D, Murillas, J, Romero, A, Agustí, C, Agüero, F, Ferrer, E, Riera, M, Segura, F, Navarro, G, Force, L, Vilaró, J, Masabeu, A, García, I, Guadarrama, M, Montoliu, A, Ortega, N, Lazzari, E, Puchol, E, Sanchez, M, Blanco, Jl, Garcia Alcaide, F, Martinez, E, Mallolas, J, López Dieguez, M, García Goez, Jf, Sirera, G, Romeu, J, Negredo, E, Miranda, C, Capitan, Mc, Olmo, M, Barragan, P, Saumoy, M, Bolao, F, Cabellos, C, Peña, C, Sala, M, Cervantes, M, Jose Amengual, M, Navarro, M, Penelo, E, Barrufet, P, Raper, Jl, Mugavero, Mj, Willig, Jh, Schumacher, J, Chang, Pw, Westfall, Ao, Cloud, G, Lin, Hy, Acosta, Ep, Colette Kempf, M, Allison, Jj, Pisu, M., Amsterdam institute for Infection and Immunity, Amsterdam Public Health, Infectious diseases, Other departments, General Internal Medicine, Graduate School, Global Health, Paediatric Infectious Diseases / Rheumatology / Immunology, and Medical Microbiology and Infection Prevention

Subjects
Male, Infectious diseases and international health [NCEBP 13], Lymphoma, 030312 virology, Esophageal candidiasis, Cohort Studies, 0302 clinical medicine, Interquartile range, 030212 general & internal medicine, AIDS-Related, Lymphoma, AIDS-Related, 0303 health sciences, Mortality rate, Progressive multifocal leukoencephalopathy, Hazard ratio, Prognosis, 3. Good health, Pathogenesis and modulation of inflammation [N4i 1], Infectious Diseases, Combination, Drug Therapy, Combination, Female, Infection and autoimmunity [NCMLS 1], Human, Microbiology (medical), Adult, medicine.medical_specialty, Prognosi, Anti-HIV Agents, antiretroviral therapy, Infectious Disease, Article, AIDS-Related Opportunistic Infection, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), Drug Therapy, Internal medicine, medicine, Humans, AIDS-defining event, Proportional Hazards Models, AIDS-Related Opportunistic Infections/diagnosis/ mortality, Acquired Immunodeficiency Syndrome/complications/diagnosis/drug, therapy/ mortality, Anti-HIV Agents/ therapeutic use, AIDS-Related/diagnosis/mortality, Acquired Immunodeficiency Syndrome, AIDS-Related Opportunistic Infections, business.industry, Proportional hazards model, Poverty-related infectious diseases [N4i 3], Anti-HIV Agent, medicine.disease, mortality, Confidence interval, Immunology, Proportional Hazards Model, Cohort Studie, business
Abstract

Contains fulltext : 80963.pdf (Publisher’s version ) (Open Access) BACKGROUND: The extent to which mortality differs following individual acquired immunodeficiency syndrome (AIDS)-defining events (ADEs) has not been assessed among patients initiating combination antiretroviral therapy. METHODS: We analyzed data from 31,620 patients with no prior ADEs who started combination antiretroviral therapy. Cox proportional hazards models were used to estimate mortality hazard ratios for each ADE that occurred in >50 patients, after stratification by cohort and adjustment for sex, HIV transmission group, number of antiretroviral drugs initiated, regimen, age, date of starting combination antiretroviral therapy, and CD4+ cell count and HIV RNA load at initiation of combination antiretroviral therapy. ADEs that occurred in

Published
2009

11. TEMPORAL CHANGES IN HEPATITIS C VIRUS GENOTYPE 3A DISTRIBUTION AMONG PEOPLE WHO INJECT DRUGS IN VANCOUVER, CANADA

Author

Jacka, B, Applegate, T, Poon, AF, Harrigan, R, Dore, GJ, Olmstead, A, DeBeck, K, Milloy, M-J, Lamoury, F, Woods, C, Brumme, Z, Dobrer, S, Lima, VD, Montaner, J, Joy, J, Marshall, BD, Kerr, T, Wood, E, Krajden, M, Grebely, J, Jacka, B, Applegate, T, Poon, AF, Harrigan, R, Dore, GJ, Olmstead, A, DeBeck, K, Milloy, M-J, Lamoury, F, Woods, C, Brumme, Z, Dobrer, S, Lima, VD, Montaner, J, Joy, J, Marshall, BD, Kerr, T, Wood, E, Krajden, M, and Grebely, J

Published
2014

12. Transmitted escape mutations lead to accelerated HIV-1 disease progression and largely define the relative contribution of HLA Alleles to control

Author

Carlson, J.M., Schaefer, M., Brumme, C., Pfeifer, N., Shapiro, R., Ndung'u, T., Frater, J., Mallal, S., John, M., Heckerman, D., Goulder, P., Brumme, Z., Hunter, E., Carlson, J.M., Schaefer, M., Brumme, C., Pfeifer, N., Shapiro, R., Ndung'u, T., Frater, J., Mallal, S., John, M., Heckerman, D., Goulder, P., Brumme, Z., and Hunter, E.

Abstract

No abstract available

Published
2014

16. Differential Escape Patterns within the Dominant HLA-B*57:03-Restricted HIV Gag Epitope Reflect Distinct Clade-Specific Functional Constraints

Author

Payne, R. P., primary, Branch, S., additional, Kløverpris, H., additional, Matthews, P. C., additional, Koofhethile, C. K., additional, Strong, T., additional, Adland, E., additional, Leitman, E., additional, Frater, J., additional, Ndung'u, T., additional, Hunter, E., additional, Haubrich, R., additional, Mothe, B., additional, Edwards, A., additional, Riddell, L., additional, Chen, F., additional, Harrigan, P. R., additional, Brumme, Z. L., additional, Mallal, S., additional, John, M., additional, Jooste, J. P., additional, Shapiro, R., additional, Deeks, S. G., additional, Walker, B. D., additional, Brander, C., additional, Landis, C., additional, Carlson, J. M., additional, Prado, J. G., additional, and Goulder, P. J. R., additional

Published
2014
Full Text
View/download PDF

17. P762 TEMPORAL CHANGES IN HEPATITIS C VIRUS GENOTYPE 3A DISTRIBUTION AMONG PEOPLE WHO INJECT DRUGS IN VANCOUVER, CANADA

Author

Jacka, B., primary, Applegate, T., additional, Poon, A.F., additional, Harrigan, R., additional, Dore, G.J., additional, Olmstead, A., additional, DeBeck, K., additional, Milloy, M.-J., additional, Lamoury, F., additional, Woods, C., additional, Brumme, Z., additional, Dobrer, S., additional, Dias Lima, V., additional, Montaner, J., additional, Joy, J., additional, Marshall, B.D., additional, Kerr, T., additional, Wood, E., additional, Krajden, M., additional, and Grebely, J., additional

Published
2014
Full Text
View/download PDF

18. Distinct HIV-1 Escape Patterns Selected by Cytotoxic T Cells with Identical Epitope Specificity

Author

Yagita, Y., Kuse, N., Kuroki, K., Gatanaga, H., Carlson, J. M., Chikata, T., Brumme, Z. L., Murakoshi, H., Akahoshi, T., Pfeifer, N., Mallal, S., John, M., Ose, T., Matsubara, H., Kanda, R., Fukunaga, Y., Honda, K., Kawashima, Y., Ariumi, Y., Oka, S., Maenaka, K., Takiguchi, M., Yagita, Y., Kuse, N., Kuroki, K., Gatanaga, H., Carlson, J. M., Chikata, T., Brumme, Z. L., Murakoshi, H., Akahoshi, T., Pfeifer, N., Mallal, S., John, M., Ose, T., Matsubara, H., Kanda, R., Fukunaga, Y., Honda, K., Kawashima, Y., Ariumi, Y., Oka, S., Maenaka, K., and Takiguchi, M.

Abstract

Pol283-8-specific, HLA-B*51:01-restricted, cytotoxic T cells (CTLs) play a critical role in the long-term control of HIV-1 infection. However, these CTLs select for the reverse transcriptase (RT) I135X escape mutation, which may be accumulating in circulating HIV-1 sequences. We investigated the selection of the I135X mutation by CTLs specific for the same epitope but restricted by HLA-B*52:01. We found that Pol283-8-specific, HLA-B*52:01-restricted CTLs were elicited predominantly in chronically HIV-1-infected individuals. These CTLs had a strong ability to suppress the replication of wild-type HIV-1, though this ability was weaker than that of HLA-B*51:01-restricted CTLs. The crystal structure of the HLA-B*52:01-Pol283-8 peptide complex provided clear evidence that HLA-B*52:01 presents the peptide similarly to HLA-B*51:01, ensuring the cross-presentation of this epitope by both alleles. Population level analyses revealed a strong association of HLA-B*51:01 with the I135T mutant and a relatively weaker association of HLA-B*52:01 with several I135X mutants in both Japanese and predominantly Caucasian cohorts. An in vitro viral suppression assay revealed that the HLA-B*52:01-restricted CTLs failed to suppress the replication of the I135X mutant viruses, indicating the selection of these mutants by the CTLs. These results suggest that the different pattern of I135X mutant selection may have resulted from the difference between these two CTLs in the ability to suppress HIV-1 replication.

Published
2013

19. Limited evidence for alterations in Gag-mediated HIV replication capacity over the course of the North American epidemic (1979-present)

Author

Cotton, L., Chopera, D., Penney, K., Carlson, J., Martin, E., Le, A., Kuang, T., Walker, B., Fuchs, J., Buchbinder, S., Wagner, T., John, M., Mallal, S., Koblin, B., Mayer, K., Poon, A., Brockman, M., Brumme, Z., Cotton, L., Chopera, D., Penney, K., Carlson, J., Martin, E., Le, A., Kuang, T., Walker, B., Fuchs, J., Buchbinder, S., Wagner, T., John, M., Mallal, S., Koblin, B., Mayer, K., Poon, A., Brockman, M., and Brumme, Z.

Abstract

The extent to which HIV replication capacity (RC) has changed over the epidemic’s course, and the influence of HLA-associated immune pressure as its driving force remains unknown. We performed a comparative study of immune escape and RC in historic (1979-1989) and modern Gag subtype B sequences from North America.

Published
2012

20. Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B*2705-restricted CD8+ T cells

Author

Payne, R.P., Kløverpris, Henrik, Sacha, J.B., Brumme, Z., Brumme, C., Buus, Søren, Sims, S., Hickling, S., Riddell, L., Chen, F., Luzzi, G., Edwards, A., Phillips, R., Prado, J.G., Goulder, P.J.R., Payne, R.P., Kløverpris, Henrik, Sacha, J.B., Brumme, Z., Brumme, C., Buus, Søren, Sims, S., Hickling, S., Riddell, L., Chen, F., Luzzi, G., Edwards, A., Phillips, R., Prado, J.G., and Goulder, P.J.R.

Published
2010

21. HLA-Associated viral mutations are common in human immunodeficiency virus type 1 elite controllers

Author

Miura, T., Brumme, C. J., Brockman, M. A., Brumme, Z. L., Pereyra, F., Block, B. L., Trocha, A., John, M., Mallal, S., Harrigan, P. R., Walker, B. D., Miura, T., Brumme, C. J., Brockman, M. A., Brumme, Z. L., Pereyra, F., Block, B. L., Trocha, A., John, M., Mallal, S., Harrigan, P. R., and Walker, B. D.

Abstract

Elite controllers (EC) of human immunodeficiency virus type 1 (HTV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8+ T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear. We obtained plasma gag, pol, and nef sequences from HLA-diverse subjects and found that 30 to 40% of the predefined HLA-associated polymorphic sites show evidence of immune selection pressure in EC., compared to approximately 50% of the sites in chronic progressors. These data indicate ongoing viral replication and escape from cytotoxic T lymphocytes are present even in strictly controlled HTV-1 infection.

Published
2009

22. Adaptation of HIV-1 to human leukocyte antigen class I

Author

Kawashima, Y., Pfafferott, K., Frater, J., Matthews, P., Payne, R., Addo, M., Gatanaga, H., Fujiwara, M., Hachiya, A., Koizumi, H., Kuse, N., Oka, S., Duda, A., Prendergast, A., Crawford, H., Leslie, A., Brumme, Z., Brumme, C., Allen, T., Brander, C., Kaslow, R., Tang, J., Hunter, E., Allen, S., Mulenga, J., Branch, S., Roach, T., John, M., Mallal, S., Ogwu, A., Shapiro, R., Prado, J.G., Fidler, S., Weber, J., Pybus, O.G., Klenerman, P., Ndung’u, T., Phillips, R., Heckerman, D., Harrigan, P.R., Walker, Bruce D., Takiguchi, M., Goulder, P., Kawashima, Y., Pfafferott, K., Frater, J., Matthews, P., Payne, R., Addo, M., Gatanaga, H., Fujiwara, M., Hachiya, A., Koizumi, H., Kuse, N., Oka, S., Duda, A., Prendergast, A., Crawford, H., Leslie, A., Brumme, Z., Brumme, C., Allen, T., Brander, C., Kaslow, R., Tang, J., Hunter, E., Allen, S., Mulenga, J., Branch, S., Roach, T., John, M., Mallal, S., Ogwu, A., Shapiro, R., Prado, J.G., Fidler, S., Weber, J., Pybus, O.G., Klenerman, P., Ndung’u, T., Phillips, R., Heckerman, D., Harrigan, P.R., Walker, Bruce D., Takiguchi, M., and Goulder, P.

Abstract

The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8 + T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection. Mutation within these epitopes can allow viral escape from CD8 + T-cell recognition. Here we analysed viral sequences and HLA alleles from 2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128-135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8 + T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV. © 2009 Macmillan Publishers Limited. All rights reserved.

Published
2009

23. Marked epitope- and allele-specific differences in rates of mutation in human immunodeficiency type 1 (HIV-1) Gag, Pol, and Nef cytotoxic T-lymphocyte epitopes in acute/early HIV-1 infection

Author

Brumme, Z. L., Brumme, C. J., Carlson, J., Streeck, H., John, M., Eichbaum, Q., Block, B. L., Baker, B., Kadie, C., Markowitz, M., Jessen, H., Kelleher, A. D., Rosenberg, E., Kaldor, J., Yuki, Y., Carrington, M., Allen, T. M., Mallal, S., Altfeld, M., Heckerman, D., Walker, B. D., Brumme, Z. L., Brumme, C. J., Carlson, J., Streeck, H., John, M., Eichbaum, Q., Block, B. L., Baker, B., Kadie, C., Markowitz, M., Jessen, H., Kelleher, A. D., Rosenberg, E., Kaldor, J., Yuki, Y., Carrington, M., Allen, T. M., Mallal, S., Altfeld, M., Heckerman, D., and Walker, B. D.

Abstract

During acute human immunodeficiency virus type 1 (HIV-1) infection, early host cellular immune responses drive viral evolution. The rates and extent of these mutations, however, remain incompletely characterized. In a cohort of 98 individuals newly infected with HIV-1 subtype B, we longitudinally characterized the rates and extent of HLA-mediated escape and reversion in Gag, Pol, and Nef using a rational definition of HLA-attributable mutation based on the analysis of a large independent subtype B data set. We demonstrate rapid and dramatic HIV evolution in response to immune pressures that in general reflect established cytotoxic T-lymphocyte (CTL) response hierarchies in early infection. On a population level, HLA-driven evolution was observed in ∼80% of published CTL epitopes. Five of the 10 most rapidly evolving epitopes were restricted by protective HLA alleles (HLA-B*13/B*51/B*57/B*5801; P = 0.01), supporting the importance of a strong early CTL response in HIV control. Consistent with known fitness costs of escape, B*57-associated mutations in Gag were among the most rapidly reverting positions upon transmission to non-B*57-expressing individuals, whereas many other HLA-associated polymorphisms displayed slow or negligible reversion. Overall, an estimated minimum of 30% of observed substitutions in Gag/Pol and 60% in Nef were attributable to HLA-associated escape and reversion events. Results underscore the dominant role of immune pressures in driving early within-host HIV evolution. Dramatic differences in escape and reversion rates across codons, genes, and HLA restrictions are observed, highlighting the complexity of viral adaptation to the host immune response.

Published
2008

27. P09-20 LB. Ultra-deep sequencing of full-length HIV-1 genomes identifies rapid viral evolution during acute infection

Author

Henn, MR, primary, Boutwell, C, additional, Lennon, N, additional, Power, K, additional, Malboeuf, C, additional, Charlebois, P, additional, Gladden, A, additional, Levin, J, additional, Casali, M, additional, Philips, L, additional, Berlin, A, additional, Berical, A, additional, Erlich, R, additional, Anderson, S, additional, Streeck, H, additional, Kemper, M, additional, Ryan, E, additional, Wang, Y, additional, Green, L, additional, Axten, K, additional, Brumme, Z, additional, Brumme, C, additional, Russ, C, additional, Rosenberg, E, additional, Jessen, H, additional, Altfeld, M, additional, Nusbaum, C, additional, Walker, B, additional, Birren, B, additional, and Allen, TM, additional

Published
2009
Full Text
View/download PDF

33. Influence of Gag-Protease-Mediated Replication Capacity on Disease Progression in Individuals Recently Infected with HIV-1 Subtype C

Author

Wright, J. K., Novitsky, Vladimir A., Brockman, M. A., Brumme, Z. L., Brumme, C. J., Carlson, J. M., Heckerman, D., Wang, B., Losina, E., Leshwedi, M., van der Stok, M., Maphumulo, L., Mkhwanazi, N., Chonco, F., Goulder, P. J. R., Essex, Myron Elmer, Walker, B. D., and Ndung, T.

Abstract

HLA class I-mediated selection of immune escape mutations in functionally important Gag epitopes may partly explain slower disease progression in HIV-1-infected individuals with protective HLA alleles. To investigate the impact of Gag function on disease progression, the replication capacities of viruses encoding Gag-protease from 60 individuals in early HIV-1 subtype C infection were assayed in an HIV-1-inducible green fluorescent protein reporter cell line and were correlated with subsequent disease progression. Replication capacities did not correlate with viral load set points (P = 0.37) but were significantly lower in individuals with below-median viral load set points (P = 0.03), and there was a trend of correlation between lower replication capacities and lower rates of CD4 decline (P = 0.09). Overall, the proportion of host HLA-specific Gag polymorphisms in or adjacent to epitopes was negatively associated with replication capacities (P = 0.04), but host HLA-B-specific polymorphisms were associated with higher viral load set points (P = 0.01). Further, polymorphisms associated with host-specific protective HLA alleles were linked with higher viral load set points (P = 0.03). These data suggest that transmission or early HLA-driven selection of Gag polymorphisms results in reduced early cytotoxic T-lymphocyte (CTL) responses and higher viral load set points. In support of the former, 46% of individuals with nonprotective alleles harbored a Gag polymorphism exclusively associated with a protective HLA allele, indicating a high rate of their transmission in sub-Saharan Africa. Overall, HIV disease progression is likely to be affected by the ability to mount effective Gag CTL responses as well as the replication capacity of the transmitted virus.

Published
2011
Full Text
View/download PDF

34. A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control

Author

Bartha, I., Carlson, J. M., Brumme, C. J., McLaren, P. J., Brumme, Z. L., John, M., Haas, D. W., Martinez-Picado, J., Dalmau, J., Lopez-Galindez, C., Casado, C., Rauch, Andri, Gunthard, H. F., Bernasconi, E., Vernazza, P., Klimkait, T., Yerly, S., O'Brien, S. J., Listgarten, J., Pfeifer, N., Lippert, C., Fusi, N., Kutalik, Z., Allen, T. M., Muller, V., Harrigan, P. R., Heckerman, D., Telenti, A., and Fellay, J.

Subjects
610 Medicine & health, 3. Good health
Abstract

HIV-1 sequence diversity is affected by selection pressures arising from host genomic factors. Using paired human and viral data from 1071 individuals, we ran >3000 genome-wide scans, testing for associations between host DNA polymorphisms, HIV-1 sequence variation and plasma viral load (VL), while considering human and viral population structure. We observed significant human SNP associations to a total of 48 HIV-1 amino acid variants (p

35. Incidence of tuberculosis among HIV-infected patients receiving highly active antiretroviral therapy in Europe and North America

Author

Costagliola, D., Dabis, F., Monforte, Ad, Wolf, F., Egger, M., Fatkenheuer, G., Gill, J., Hogg, R., Justice, A., Ledergerber, B., Lundgren, J., May, M., Phillips, A., Reiss, P., Sabin, C., Staszewski, S., Sterne, J., Weller, I., Beckthold, B., Yip, B., Dauer, B., Fusco, J., Grabar, S., Lanoy, E., Junghans, C., Lavignolle, V., Leth, F., Pereira, E., Pezzotti, P., Schmeisser, N., Billaud, E., Boue, F., Duval, X., Duvivier, C., Enel, P., Fournier, S., Gasnault, J., Gaud, C., Gilquin, J., Khuong, Ma, Lang, Jm, Mary-Krause, M., Matheron, S., Meyohas, Mc, Pialoux, G., Poizot-Martin, I., Pradier, C., Rouveix, E., Salmon-Ceron, D., Sobel, A., Tattevin, P., Tissot-Dupont, H., Yasdanpanah, Y., Aronica, E., Tirard-Fleury, V., Tortay, I., Abgrall, S., Guiguet, M., Leneman, H., Lievre, L., Potard, V., Saidi, S., Vilde, Jl, Leport, C., Yeni, P., Bouvet, E., Gaudebout, C., Crickx, B., Picard-Dahan, C., Weiss, L., Tisne-Dessus, D., Sicard, D., Salmon, D., Auperin, I., Viard, Jp, Roudiere, L., Delfraissy, Jf, Goujard, C., Lesprit, P., Jung, C., Meynard, Jl, Picard, O., Desplanque, N., Cadranel, J., Mayaud, C., Rozenbaum, W., Bricaire, F., Katlama, C., Herson, S., Simon, A., Decazes, Jm, Molina, Jm, Clauvel, Jp, Gerard, L., Widal, Ghlf, Sellier, P., Diemer, M., Dupont, C., Berthe, H., Saiag, P., Mortier, L., Mortier, E., Chandemerle, C., Truchis, P., Bentata, M., Honore, P., Tassi, S., Jeantils, V., Mechali, D., Taverne, B., Laurichesse, H., Gourdon, F., Lucht, F., Fresard, A., Faller, Jp, Eglinger, P., Bazin, C., Verdon, R., Peyramond, D., Boibieux, A., Touraine, Jl, Livrozet, Jm, Trepo, C., Cotte, L., Ravaux, I., Delmont, Jp, Moreau, J., Gastaut, Ja, Soubeyrand, J., Retornaz, F., Blanc, Pa, Allegre, T., Galinier, A., Ruiz, Jm, Lepeu, G., Granet-Brunello, P., Pelissier, L., Esterni, Jp, Nezri, M., Cohen-Valensi, R., Laffeuillade, A., Chadapaud, S., Reynes, J., May, T., Rabaud, C., Raffi, F., Pugliese, P., Michelet, C., Arvieux, C., Caron, F., Borsa-Lebas, F., Fraisse, P., Massip, P., Cuzin, L., Arlet-Suau, E., Legrand, Mft, Sobesky, M., Pradinaud, R., Guyon, F., Contant, M., Montroni, M., Scalise, G., Braschi, Mc, Aviano, Ar, Tirelli, U., Cinelli, R., Pastore, G., Ladisa, N., Minafra, G., Suter, F., Arici, C., Chiodo, F., Colangeli, V., Fiorini, C., Coronado, O., Carosi, G., Cadeo, Gp, Torti, C., Minardi, C., Bertelli, D., Rizzardini, G., Melzi, S., Manconi, Pe, Catanzaro, Pp, Cosco, L., Scerbo, A., Vecchiet, J., D Alessandro, M., Santoro, D., Pusterla, L., Carnevale, G., Citterio, P., Vigano, P., Mena, M., Ghinelli, F., Sighinolfi, L., Leoncini, F., Mazzotta, F., Pozzi, M., Lo Caputo, S., Angarano, G., Grisorio, B., Saracino, A., Ferrara, S., Grima, P., Tundo, P., Pagano, G., Cassola, G., Alessandrini, A., Piscopo, R., Toti, M., Chigiotti, S., Soscia, F., Tacconi, L., Orani, A., Perini, P., Scasso, A., Vincenti, A., Chiodera, F., Castelli, P., Scalzini, A., Palvarini, L., Moroni, M., Lazzarin, A., Cargnel, A., Vigevani, Gm, Caggese, L., Repetto, D., Galli, A., Merli, S., Pastecchia, C., Moioli, Mc, Esposito, R., Mussini, C., Abrescia, N., Chirianni, A., Izzo, Cm, Piazza, M., Marco, M., Viglietti, R., Manzillo, E., Nappa, S., Colomba, A., Abbadessa, V., Prestileo, T., Mancuso, S., Ferrari, C., Pizzaferri, P., Filice, G., Minoli, L., Bruno, R., Novati, S., Baldelli, F., Tinca, M., Petrelli, E., Cioppi, A., Alberici, F., Ruggieri, A., Menichetti, F., Martinelli, C., Stefano, C., La Gala, A., Ballardini, G., Rizzo, E., Magnani, G., Ursitti, Ma, Arlotti, M., Ortolani, P., Cauda, R., Dianzani, F., Ippolito, G., Antinori, A., Antonucci, G., D Elia, S., Narciso, P., Petrosillo, N., Vullo, V., Luca, A., Bacarelli, A., Zaccarelli, M., Acinapura, R., Longis, P., Brandi, A., Trotta, Mp, Noto, P., Lichtner, M., Capobianchi, MR, Carletti, F., Girardi, E., Rezza, G., Mura, Ms, Mannazzu, M., Caramello, P., Di Perri, G., Soranzo, Ml, Orofino, Gc, Arnaudo, I., Bonasso, M., Grossi, Pa, Basilico, C., Poggio, A., Bottari, G., Raise, E., Ebo, F., Lalla, F., Tositti, G., Resta, F., Loso, K., Lepri, Ac, Battegay, M., Bernasconi, E., Boni, J., Bucher, H., Burgisser, P., Cattacin, S., Cavassini, M., Dubs, R., Elzi, L., Erb, P., Fantelli, K., Fischer, M., Flepp, M., Fontana, A., Francioli, P., Furrer, H., Gorgievski, M., Hirschel, B., Kaiser, L., Kind, C., Klimkait, T., Lauper, U., Opravil, M., Paccaud, F., Pantaleo, G., Perrin, L., Piffaretti, Jc, Rickenbach, M., Rudin, C., Schmid, P., Schupbach, J., Speck, R., Telenti, A., Trkola, A., Vernazza, P., Weber, R., Yerly, S., Bronsveld, W., Hillebrand-Haverkort, Me, Prins, Jm, Bos, Jc, Schattenkerk, Jkme, Geerlings, Se, Godfried, Mh, Lange, Jma, Leth, Fc, Lowe, Sh, Meer, Jtm, Nellen, Fjb, Pogany, K., Poll, T., Ruys, Ta, Sankatsing, S., Steingrover, R., Twillert, G., Valk, M., Vonderen, Mga, Vrouenraets, Sme, Vugt, M., Wit, Fwmn, Kuijpers, Tw, Pajkrt, D., Scherpbier, Hj, Eeden, A., Ten Veen, Jh, Dam, Ps, Roos, Jc, Brinkman, K., Frissen, Phj, Weigel, Hm, Mulder, Jw, Gorp, Ecm, Meenhorst, Pl, Mairuhu, Ata, Ziekenhuis, S., Veenstra, J., Danner, Sa, Agtmael, Ma, Claessen, Fap, Perenboom, Rm, Rijkeboer, A., Vonderen, M., Richter, C., Berg, J., Leusen, R., Vriesendorp, R., Jeurissen, Fjf, Kauffmann, Rh, Koger, Elw, Bravenboer, B., Ten Napel, Chh, Kootstra, Gj, Sprenger, Hg, Miesen, Wmaj, Doedens, R., Scholvinck, Eh, Ten Kate, Rw, Houte, Dpf, Polee, M., Kroon, Fp, van den Broek, Dissel, Jt, Schippers, Ef, Schreij, G., Geest, Sv, Verbon, A., Koopmans, Pp, Keuter, M., Post, F., Ven, Ajam, Ende, Me, Gyssens, Ic, Feltz, M., Den Hollander, Jg, Marie, S., Nouwen, Jl, Rijnders, Bja, Vries, Tems, Driessen, G., Groot, R., Hartwig, N., Juttmann, Jr, Heul, C., Kasteren, Mee, Schneider, Mme, Bonten, Mjm, Borleffs, Jcc, Ellerbroek, Pm, Hoepelman, Im, Jaspers, Cajj, Schouten, I., Schurink, Cam, Geelen, Spm, Wolfs, Tfw, Blok, Wl, Tanis, Aa, Groeneveld, Php, Klinieken-Zwolle, I., Back, Nkt, Bakker, Meg, Berkhout, B., Jurriaans, S., Cuijpers, T., Rietra, Pjgm, Roozendaal, Kj, Pauw, W., Zanten, Ap, Blomberg, Bme, Savelkoul, P., Swanink, Cma, Franck, Pfh, Lampe, As, Hendriks, R., Schirm, J., Veenendaal, D., Storm, H., Weel, J., Zeijl, H., Kroes, Acm, Claas, Hcj, Bruggeman, Camva, Goossens, Vj, Galama, Jmd, Melchers, Wjg, Poort, Yag, Doornum, Gjj, Niesters, Mg, Osterhaus, Adme, Schutten, M., Buiting, Agm, Swaans, Cam, Boucher, Cab, Boel, E., Jansz, Af, Losso, M., Duran, A., Vetter, N., Karpov, I., Vassilenko, A., Clumeck, N., Wit, S., Poll, B., Colebunders, R., Machala, L., Rozsypal, H., Dalibor Sedlacek, Nielsen, J., Benfield, T., Kirk, O., Gerstoft, J., Katzenstein, T., Hansen, Abe, Skinhoj, P., Pedersen, C., Zilmer, K., Girard, Pm, Saint-Marc, T., Vanhems, P., Dietrich, M., Manegold, C., Lunzen, J., Stellbrink, Hj, Bickel, M., Goebel, Fd, Rockstroh, J., Schmidt, R., Kosmidis, J., Gargalianos, P., Sambatakou, H., Perdios, J., Panos, G., Filandras, A., Karabatsaki, E., Banhegyi, D., Mulcahy, F., Yust, I., Turner, D., Burke, M., Pollack, S., Hassoun, G., Sthoeger, Z., Maayan, S., Chiesi, A., Borghi, R., Pristera, R., Gabbuti, A., Montesarchio, E., Iacomi, F., Finazzi, R., Viksna, L., Chaplinskas, S., Hemmer, R., Staub, T., Bruun, J., Maeland, A., Ormaasen, V., Knysz, B., Gasiorowski, J., Horban, A., Prokopowicz, D., Wiercinska-Drapalo, A., Boron-Kaczmarska, A., Pynka, M., Beniowski, M., Mularska, E., Trocha, H., Antunes, F., Valadas, E., Mansinho, K., Matez, F., Duiculescu, D., Babes, V., Streinu-Cercel, A., Vinogradova, E., Rakhmanova, A., Jevtovic, D., Mokras, M., Stanekova, D., Gonzalez-Lahoz, J., Sanchez-Conde, M., Garcia-Benayas, T., Martin-Carbonero, L., Soriano, V., Clotet, B., Jou, A., Conejero, J., Tural, C., Gatell, Jm, Miro, Jm, Blaxhult, A., Karlsson, A., Pehrson, P., Soravia-Dunand, V., Kravchenko, E., Chentsova, N., Barton, S., Johnson, Am, Mercey, D., Johnson, Ma, Mocroft, A., Murphy, M., Weber, J., Scullard, G., Fisher, M., Brettle, R., Loveday, C., Gatell, J., Johnson, A., Vella, S., Gjorup, I., Friis-Moeller, N., Cozzi-Lepri, A., Bannister, W., Mollerup, D., Podlevkareva, D., Olsen, Ch, Kjaer, J., Raffanti, S., Dieterch, D., Becker, S., Scarsella, A., Fusco, G., Most, B., Balu, R., Rana, R., Beckerman, R., Ising, T., Irek, R., Johnson, B., Hirani, A., Dejesus, E., Pierone, G., Lackey, P., Irek, C., Burdick, J., Leon, S., Arch, J., Helm, Eb, Carlebach, A., Muller, A., Haberl, A., Nisius, G., Lennemann, T., Rottmann, C., Wolf, T., Stephan, C., Mosch, M., Gute, P., Locher, L., Lutz, T., Klauke, S., Knecht, G., Doerr, Hw, Sturmer, M., Hentig, N., Jennings, B., Beylot, J., Chene, G., Dupon, M., Longy-Boursier, M., Pellegrin, Jl, Ragnaud, Jm, Salamon, R., Thiebaut, R., Lewden, C., Lawson-Ayayi, S., Mercie, P., Moreau, Jf, Moriat, P., Bernard, N., Lacoste, D., Malvy, D., Neau, D., Blaizeau, Mj, Decoin, M., Delveaux, S., Hannapier, C., Labarrere, S., Lavignolle-Aurillac, V., Uwamaliya-Nziyumvira, B., Palmer, G., Touchard, D., Balestre, E., Alioum, A., Jacqmin-Gadda, H., Morlat, P., Bonarek, M., Bonnet, F., Coadou, B., Gellie, P., Nouts, C., Bocquentin, F., Dutronc, H., Lafarie, S., Aslan, A., Pistonne, T., Thibaut, P., Vatan, R., Chambon, D., La Taille, C., Cazorla, C., Ocho, A., Castera, L., Fleury, H., Lafon, Me, Masquelier, B., Pellegrin, I., Breilh, D., Blanco, P., Loste, P., Caunegre, L., Bonnal, F., Farbos, S., Ferrand, M., Ceccaldi, J., Tchamgoue, S., Witte, S., Buy, E., Alexander, C., Barrios, R., Braitstein, P., Brumme, Z., Chan, K., Cote, H., Gataric, N., Geller, J., Guillemi, S., Harrigan, Harris, M., Joy, R., Levy, A., Montaner, J., Montessori, V., Palepu, A., Phillips, E., Phillips, P., Press, N., Tyndall, M., Wood, E., Ballinger, J., Bhagani, S., Breen, R., Byrne, P., Carroll, A., Cropley, I., Cuthbertson, Z., Drinkwater, T., Fernandez, T., Geretti, Am, Murphy, G., Ivens, D., Johnson, M., Kinloch-De Loes, S., Lipman, M., Madge, S., Prinz, B., Bell, Dr, Shah, S., Swaden, L., Tyrer, M., Youle, M., Chaloner, C., Gumley, H., Holloway, J., Puradiredja, D., Sweeney, J., Tsintas, R., Bansi, L., Fox, Z., Lampe, F., Smith, C., Amoah, E., Clewley, G., Dann, L., Gregory, B., Jani, I., Janossy, G., Kahan, M., Thomas, M., Gill, Mj, Read, R., Schmeisser, V., Voigt, K., Wasmuth, Jc, Wohrmann, A., and Antiretroviral Therapy Cohort Coll

36. T cell receptor clonotypes modulate the protective effect of human leukocyte antigen class I alleles in HIV-1 infection.

Author

H. Chen, Ndhlovu, Z. M., Liu, D., Porter, L. C., Fang, J. W., Darko, S., Brockman, M. A., Miura, T., Brumme, Z. L., Schneidewind, A., Piechocka-Trocha, A., Cesa, K. T., Sela, J., Cung, T. D., Toth, I., Pereyra, F., Yu, X. G., Douek, D. C., Kaufmann, D. E., and Allen, T. M.

Subjects
T cell receptors
Abstract

An abstract of the research paper "T cell receptor clonotypes modulate the protective effect of human leukocyte antigen class I alleles in HIV-1 infection," by H. Chen and colleagues is presented.

Published
2012
Full Text
View/download PDF

37. HLA-associated viral polymorphism in chronically HIV-1-infected Japanese cohort: analysis of four-digit HLA allele level.

Author

Chikata, T., Carlson, J. M., Tamura, Y., Brumme, Z. L., Naruto, T., Hashimoto, M., Borghan, M. A., John, M., Mallal, S., Gatanaga, H., Oka, S., and Takiguchi, M.

Subjects
ISOHORMONES
Abstract

An abstract of the research paper "HLA-associated viral polymorphism in chronically HIV-1-infected Japanese cohort: analysis of four-digit HLA allele level," by T. Chikata and colleagues is presented.

Published
2012
Full Text
View/download PDF

38. CTN 328: immunogenicity outcomes in people living with HIV in Canada following vaccination for COVID-19 (HIV-COV): protocol for an observational cohort study.

Author

Costiniuk CT, Singer J, Langlois MA, Kulic I, Needham J, Burchell A, Jenabian MA, Walmsley S, Ostrowski M, Kovacs C, Tan D, Harris M, Hull M, Brumme Z, Brockman M, Margolese S, Mandarino E, Angel JB, Routy JP, Anis AH, and Cooper C

Subjects
Humans, Canada, Cohort Studies, COVID-19 Vaccines, Diterpenes, Multicenter Studies as Topic, Observational Studies as Topic, SARS-CoV-2, Vaccination, COVID-19, HIV Infections
Abstract

Introduction: Most existing vaccines require higher or additional doses or adjuvants to provide similar protection for people living with HIV (PLWH) compared with HIV-uninfected individuals. Additional research is necessary to inform COVID-19 vaccine use in PLWH., Methods and Analysis: This multicentred observational Canadian cohort study will enrol 400 PLWH aged > 16 years from Montreal, Ottawa, Toronto and Vancouver. Subpopulations of PLWH of interest will include individuals: (1) >55 years of age; (2) with CD4 counts <350 cells/mm 3 ; (3) with multimorbidity ( > 2 comorbidities) and (4) 'stable' or 'reference' PLWH (CD4 T cells >350 cells/mm 3 , suppressed viral load for > 6 months and < 1 comorbidity). Data for 1000 HIV-negative controls will be obtained via a parallel cohort study (Stop the Spread Ottawa), using similar time points and methods. Participants receiving > 1 COVID-19 vaccine will attend five visits: prevaccination; 1 month following the first vaccine dose; and at 3, 6 and 12 months following the second vaccine dose. The primary end point will be the percentage of PLWH with COVID-19-specific antibodies at 6 months following the second vaccine dose. Humoral and cell-mediated immune responses, and the interplay between T cell phenotypes and inflammatory markers, will be described. Regression techniques will be used to compare COVID-19-specific immune responses to determine whether there are differences between the 'unstable' PLWH group (CD4 <350 cells/mm3), the stable PLWH cohort and the HIV-negative controls, adjusting for factors believed to be associated with immune response. Unadjusted analyses will reveal whether there are differences in driving factors associated with group membership., Ethics and Dissemination: Research ethics boards at all participating institutions have granted ethics approval for this study. Written informed consent will be obtained from all study participants prior to enrolment. The findings will inform the design of future COVID-19 clinical trials, dosing strategies aimed to improve immune responses and guideline development for PLWH., Trial Registration Number: NCT04894448., Competing Interests: Competing interests: The authors declare that they have no competing interests, (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Published
2021
Full Text
View/download PDF

39. Impact of HLA-driven HIV adaptation on virulence in populations of high HIV seroprevalence.

Author

Payne R, Muenchhoff M, Mann J, Roberts HE, Matthews P, Adland E, Hempenstall A, Huang KH, Brockman M, Brumme Z, Sinclair M, Miura T, Frater J, Essex M, Shapiro R, Walker BD, Ndung'u T, McLean AR, Carlson JM, and Goulder PJ

Subjects
Adult, Base Sequence, Botswana epidemiology, Cohort Studies, HIV Infections transmission, HLA-B Antigens immunology, Humans, Molecular Sequence Data, Sequence Analysis, DNA, Seroepidemiologic Studies, South Africa epidemiology, Virulence, Adaptation, Biological genetics, Evolution, Molecular, HIV genetics, HIV pathogenicity, HIV Infections epidemiology, HLA-B Antigens genetics
Abstract

It is widely believed that epidemics in new hosts diminish in virulence over time, with natural selection favoring pathogens that cause minimal disease. However, a tradeoff frequently exists between high virulence shortening host survival on the one hand but allowing faster transmission on the other. This is the case in HIV infection, where high viral loads increase transmission risk per coital act but reduce host longevity. We here investigate the impact on HIV virulence of HIV adaptation to HLA molecules that protect against disease progression, such as HLA-B*57 and HLA-B*58:01. We analyzed cohorts in Botswana and South Africa, two countries severely affected by the HIV epidemic. In Botswana, where the epidemic started earlier and adult seroprevalence has been higher, HIV adaptation to HLA including HLA-B*57/58:01 is greater compared with South Africa (P = 7 × 10(-82)), the protective effect of HLA-B*57/58:01 is absent (P = 0.0002), and population viral replicative capacity is lower (P = 0.03). These data suggest that viral evolution is occurring relatively rapidly, and that adaptation of HIV to the most protective HLA alleles may contribute to a lowering of viral replication capacity at the population level, and a consequent reduction in HIV virulence over time. The potential role in this process played by increasing antiretroviral therapy (ART) access is also explored. Models developed here suggest distinct benefits of ART, in addition to reducing HIV disease and transmission, in driving declines in HIV virulence over the course of the epidemic, thereby accelerating the effects of HLA-mediated viral adaptation.

Published
2014
Full Text
View/download PDF

40. Epithelial adhesion molecules can inhibit HIV-1-specific CD8⁺ T-cell functions.

Author

Streeck H, Kwon DS, Pyo A, Flanders M, Chevalier MF, Law K, Jülg B, Trocha K, Jolin JS, Anahtar MN, Lian J, Toth I, Brumme Z, Chang JJ, Caron T, Rodig SJ, Milner DA Jr, Piechoka-Trocha A, Kaufmann DE, Walker BD, and Altfeld M

Subjects
CD8-Positive T-Lymphocytes metabolism, Cadherins immunology, Cell Adhesion Molecules immunology, Cell Adhesion Molecules metabolism, Cell Separation, Colon immunology, Colon metabolism, Enzyme-Linked Immunosorbent Assay, Female, Flow Cytometry, Fluorescent Antibody Technique, HIV Infections metabolism, HIV-1 immunology, Humans, Immunohistochemistry, Lectins, C-Type immunology, Lymphocyte Activation immunology, Male, Receptors, Immunologic, Trans-Activators immunology, Virus Replication immunology, CD8-Positive T-Lymphocytes immunology, Cadherins metabolism, HIV Infections immunology, Lectins, C-Type biosynthesis, Trans-Activators biosynthesis
Abstract

Under persistent antigenic stimulation, virus-specific CD8⁺ T cells become increasingly dysfunctional and up-regulate several inhibitory molecules such as killer lectin-like receptor G1 (KLRG1). Here, we demonstrate that HIV-1 antigen-specific T cells from subjects with chronic-progressive HIV-1 infection have significantly elevated KLRG1 expression (P < .001); show abnormal distribution of E-cadherin, the natural ligand of KLRG1, in the intestinal mucosa; and have elevated levels of systemic soluble E-cadherin (sE-cadherin) that significantly correlate with HIV-1 viral load (R = 0.7, P = .004). We furthermore demonstrate that in the presence of sE-cadherin, KLRG1(hi) HIV-1-specific CD8⁺ T cells are impaired in their ability to respond by cytokine secretion on antigenic stimulation (P = .002) and to inhibit viral replication (P = .03) in vitro. Thus, these data suggest a critical mechanism by which the disruption of the intestinal epithelium associated with HIV-1 leads to increased systemic levels of sE-cadherin, which inhibits the effector functions of KLRG1(hi)-expressing HIV-1-specific CD8⁺ T cells systemically.

Published
2011
Full Text
View/download PDF

41. Efficacious early antiviral activity of HIV Gag- and Pol-specific HLA-B 2705-restricted CD8+ T cells.

Author

Payne RP, Kløverpris H, Sacha JB, Brumme Z, Brumme C, Buus S, Sims S, Hickling S, Riddell L, Chen F, Luzzi G, Edwards A, Phillips R, Prado JG, and Goulder PJ

Subjects
AIDS Vaccines genetics, AIDS Vaccines immunology, Amino Acid Sequence, Cytotoxicity, Immunologic, Epitopes, T-Lymphocyte genetics, HIV Antigens genetics, HIV Infections virology, HIV Long-Term Survivors, Humans, Immunodominant Epitopes genetics, In Vitro Techniques, Molecular Sequence Data, Mutation, Peptide Fragments genetics, Peptide Fragments immunology, gag Gene Products, Human Immunodeficiency Virus genetics, pol Gene Products, Human Immunodeficiency Virus genetics, vpr Gene Products, Human Immunodeficiency Virus genetics, vpr Gene Products, Human Immunodeficiency Virus immunology, CD8-Positive T-Lymphocytes immunology, HIV Infections immunology, HIV-1 genetics, HIV-1 immunology, HLA-B27 Antigen metabolism, gag Gene Products, Human Immunodeficiency Virus immunology, pol Gene Products, Human Immunodeficiency Virus immunology
Abstract

The association between HLA-B 2705 and the immune control of human immunodeficiency virus type 1 (HIV-1) has previously been linked to the targeting of the HLA-B 2705-restricted Gag epitope KRWIILGLNK (KK10) by CD8(+) T cells. In order to better define the mechanisms of the HLA-B 2705 immune control of HIV, we first characterized the CD8(+) T-cell responses of nine highly active antiretroviral therapy (HAART)-naïve B 2705-positive subjects. Unexpectedly, we observed a strong response to an HLA-B 2705-restricted Pol epitope, KRKGGIGGY (KY9), in 8/9 subjects. The magnitude of the KY9 response was only marginally lower than that of the KK10-specific response (median, 695 versus 867 spot-forming cells [SFC]/million peripheral blood mononuclear cells [PBMCs]; not significant [NS]), and viral escape mutants were observed in both KY9 and KK10, resulting from selection pressure driven by the respective CD8(+) T-cell response. By comparing inhibitions of viral replication by CD8(+) T cells specific for the Gag KK10, Pol KY9, and Vpr VL9 HLA-B 2705-restricted epitopes, we observed a consistent hierarchy of antiviral efficacy (Gag KK10 > Pol KY9 > Vpr VL9). This hierarchy was associated with early recognition of HIV-1-infected cells, within 6 h of infection, by KK10- and KY9-specific CD8(+) T cells but not until 18 h postinfection by VL9-specific CD8(+) T cells. There was no association between antiviral efficacy and proliferative capacity, cytotoxicity, polyfunctionality, or T-cell receptor (TCR) avidity. These data are consistent with previous studies indicating an important role for the B 2705-Gag KK10 response in the control of HIV but also suggest a previously unrecognized role played by the subdominant Pol-specific KY9 response in HLA-B 2705-mediated control of HIV and that the recognition of HIV-infected cells by CD8(+) T cells early in the viral life cycle may be important for viral containment in HIV-infected individuals.

Published
2010
Full Text
View/download PDF

42. Impact of select immunologic and virologic biomarkers on CD4 cell count decrease in patients with chronic HIV-1 subtype C infection: results from Sinikithemba Cohort, Durban, South Africa.

Author

Brumme Z, Wang B, Nair K, Brumme C, de Pierres C, Reddy S, Julg B, Moodley E, Thobakgale C, Lu Z, van der Stok M, Bishop K, Mncube Z, Chonco F, Yuki Y, Frahm N, Brander C, Carrington M, Freedberg K, Kiepiela P, Goulder P, Walker B, Ndung'u T, and Losina E

Subjects
Adult, Alleles, Biomarkers blood, CD4-CD8 Ratio, CD8-Positive T-Lymphocytes immunology, Cohort Studies, Female, Humans, Longitudinal Studies, Male, Multivariate Analysis, Predictive Value of Tests, South Africa, CD4 Lymphocyte Count, HIV Infections immunology, HIV Infections virology, HIV-1, HLA Antigens genetics, Viral Load
Abstract

Background: The extent to which immunologic and clinical biomarkers influence human immunodeficiency virus type 1 (HIV-1) infection outcomes remains incompletely characterized, particularly for non-B subtypes. On the basis of data supporting in vitro HIV-1 protein-specific CD8 T lymphocyte responses as correlates of immune control in cross-sectional studies, we assessed the relationship of these responses, along with established HIV-1 biomarkers, with rates of CD4 cell count decrease in individuals infected with HIV-1 subtype C., Methods: Bivariate and multivariate mixed-effects models were used to assess the relationship of baseline CD4 cell count, plasma viral load, human leukocyte antigen (HLA) class I alleles, and HIV-1 protein-specific CD8 T cell responses with the rate of CD4 cell count decrease in a longitudinal population-based cohort of 300 therapy-naive, chronically infected adults with baseline CD4 cell counts >200 cells/mm(3) and plasma viral loads >500 copies/mL over a median of 25 months of follow-up., Results: In bivariate analyses, baseline CD4 cell count, plasma viral load, and possession of a protective HLA allele correlated significantly with the rate of CD4 cell count decrease. No relationship was observed between HIV-1 protein-specific CD8 T cell responses and CD4 cell count decrease. Results from multivariate models incorporating baseline CD4 cell counts (201-350 vs >350 cells/mm(3)), plasma viral load (< or =100,000 vs >100,000 copies/mL), and HLA (protective vs not protective) yielded the ability to discriminate CD4 cell count decreases over a 10-fold range. The fastest decrease was observed among individuals with CD4 cell counts >350 cells/mm(3) and plasma viral loads >100,000 copies/mL with no protective HLA alleles (-59 cells/mm(3) per year), whereas the slowest decrease was observed among individuals with CD4 cell counts 201-350 cells/mm(3), plasma viral loads < or =100,000 copies/mL, and a protective HLA allele (-6 cells/mm(3) per year)., Conclusions: The combination of plasma viral load and HLA class I type, but not in vitro HIV-1 protein-specific CD8 T cell responses, differentiates rates of CD4 cell count decrease in patients with chronic subtype-C infection better than either marker alone.

Published
2009
Full Text
View/download PDF

43. Adaptation of HIV-1 to human leukocyte antigen class I.

Author

Kawashima Y, Pfafferott K, Frater J, Matthews P, Payne R, Addo M, Gatanaga H, Fujiwara M, Hachiya A, Koizumi H, Kuse N, Oka S, Duda A, Prendergast A, Crawford H, Leslie A, Brumme Z, Brumme C, Allen T, Brander C, Kaslow R, Tang J, Hunter E, Allen S, Mulenga J, Branch S, Roach T, John M, Mallal S, Ogwu A, Shapiro R, Prado JG, Fidler S, Weber J, Pybus OG, Klenerman P, Ndung'u T, Phillips R, Heckerman D, Harrigan PR, Walker BD, Takiguchi M, and Goulder P

Subjects
Alleles, CD8-Positive T-Lymphocytes immunology, Cohort Studies, Epitopes, T-Lymphocyte chemistry, Epitopes, T-Lymphocyte genetics, Epitopes, T-Lymphocyte immunology, HIV Antigens chemistry, HIV Antigens genetics, HIV Antigens immunology, HIV-1 genetics, HIV-1 physiology, HLA-B Antigens genetics, Humans, Internationality, Polymorphism, Genetic, gag Gene Products, Human Immunodeficiency Virus chemistry, gag Gene Products, Human Immunodeficiency Virus genetics, gag Gene Products, Human Immunodeficiency Virus immunology, HIV-1 immunology, HLA-B Antigens immunology, Leukocytes immunology
Abstract

The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host-pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8(+) T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection. Mutation within these epitopes can allow viral escape from CD8(+) T-cell recognition. Here we analysed viral sequences and HLA alleles from >2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128-135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts (P = 0.0001). Extending these analyses to incorporate other well-defined CD8(+) T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants (n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.

Published
2009
Full Text
View/download PDF

44. Statistical resolution of ambiguous HLA typing data.

Author

Listgarten J, Brumme Z, Kadie C, Xiaojiang G, Walker B, Carrington M, Goulder P, and Heckerman D

Subjects
Algorithms, Alleles, Data Interpretation, Statistical, Genetics, Population, Humans, Reproducibility of Results, Sensitivity and Specificity, Gene Frequency, HLA-A Antigens genetics, Haplotypes genetics, Histocompatibility Testing methods, Polymorphism, Single Nucleotide genetics
Abstract

High-resolution HLA typing plays a central role in many areas of immunology, such as in identifying immunogenetic risk factors for disease, in studying how the genomes of pathogens evolve in response to immune selection pressures, and also in vaccine design, where identification of HLA-restricted epitopes may be used to guide the selection of vaccine immunogens. Perhaps one of the most immediate applications is in direct medical decisions concerning the matching of stem cell transplant donors to unrelated recipients. However, high-resolution HLA typing is frequently unavailable due to its high cost or the inability to re-type historical data. In this paper, we introduce and evaluate a method for statistical, in silico refinement of ambiguous and/or low-resolution HLA data. Our method, which requires an independent, high-resolution training data set drawn from the same population as the data to be refined, uses linkage disequilibrium in HLA haplotypes as well as four-digit allele frequency data to probabilistically refine HLA typings. Central to our approach is the use of haplotype inference. We introduce new methodology to this area, improving upon the Expectation-Maximization (EM)-based approaches currently used within the HLA community. Our improvements are achieved by using a parsimonious parameterization for haplotype distributions and by smoothing the maximum likelihood (ML) solution. These improvements make it possible to scale the refinement to a larger number of alleles and loci in a more computationally efficient and stable manner. We also show how to augment our method in order to incorporate ethnicity information (as HLA allele distributions vary widely according to race/ethnicity as well as geographic area), and demonstrate the potential utility of this experimentally. A tool based on our approach is freely available for research purposes at http://microsoft.com/science.

Published
2008
Full Text
View/download PDF

45. Rare mutations at codon 103 of HIV-1 reverse transcriptase can confer resistance to non-nucleoside reverse transcriptase inhibitors.

Author

Harrigan PR, Mo T, Wynhoven B, Hirsch J, Brumme Z, McKenna P, Pattery T, Vingerhoets J, and Bacheler LT

Subjects
Codon genetics, HIV Infections drug therapy, Humans, Phenotype, Polymorphism, Genetic, Reverse Transcriptase Inhibitors therapeutic use, Amino Acid Substitution genetics, Drug Resistance, Viral genetics, HIV Infections genetics, HIV Reverse Transcriptase genetics, Mutation genetics
Abstract

Background: The K103N mutation in HIV-1 reverse transcriptase (RT) confers high-level resistance to current non-nucleoside reverse transcriptase inhibitors (NNRTI). The prevalence and resistance profile of HIV-1 with other substitutions at RT codon 103 is less well documented., Methods: K103 substitutions among over 70,000 clinical samples submitted for routine antiretroviral resistance testing at two independent centres were examined. Phenotypic resistance profiles of isolates harboring rare K103 variants in the absence of known NNRTI-associated resistance mutations were retrieved from Virco's correlative genotype/phenotype database. Genotyped samples with known treatment histories were retrieved from the British Columbia Centre for Excellence in HIV/AIDS database. Site-directed mutants containing K103 variants were constructed and phenotyped., Results: K103N, R and S were observed in 29, 1.8, and 0.9% of Virco isolates and in 16, 1.5 and 0.4% of British Columbia isolates. K103T/Q/H substitutions were observed only rarely (<0.2%). The prevalence of unusual codon 103 substitutions remained stable over 5 years, except K103S, which increased over fourfold in both datasets. K103R/Q-containing clinical isolates remained phenotypically susceptible to NNRTI, whereas K103S/T/H-containing isolates showed over 10-fold decreased NNRTI susceptibility. Among patients with a known treatment history, K103S/T/H were observed primarily in individuals failing NNRTI-containing regimens. Site-directed mutants confirmed decreased susceptibility to NNRTI in K103S/T/H-containing recombinants., Conclusion: Variants at HIV RT codon 103 other than K103N are observed relatively rarely in clinical isolates, but K103 S, T and H confer decreased susceptibility to NNRTI. These data are relevant for interpretive genotype algorithms and in the design of assays specific to RT codon 103 mutations.

Published
2005
Full Text
View/download PDF

46. Insulin-like growth factor-1 protects ischemic murine myocardium from ischemia/reperfusion associated injury.

Author

Davani EY, Brumme Z, Singhera GK, Côté HC, Harrigan PR, and Dorscheid DR

Subjects
Animals, Mice, Myocardial Ischemia therapy, Myocardial Reperfusion Injury pathology, Insulin-Like Growth Factor I therapeutic use, Myocardial Reperfusion Injury prevention & control
Abstract

Introduction: Ischemia/reperfusion occurs in myocardial infarction, cardiac dysfunction during sepsis, cardiac transplantation and coronary artery bypass grafting, and results in injury to the myocardium. Although reperfusion injury is related to the nature and duration of ischemia, it is also a separate entity that may jeopardize viable cells and ultimately may impair cardiac performance once ischemia is resolved and the organ heals., Method: The present study was conducted in an ex vivo murine model of myocardial ischemia/reperfusion injury. After 20 min of ischemia, isolated hearts were perfused for up to 2 hours with solution (modified Kreb's) only, solution plus insulin-like growth factor (IGF)-1, or solution plus tumor necrosis factor (TNF)-alpha. Cardiac contractility was monitored continuously during this period of reperfusion., Results: On the basis of histologic evidence, IGF-1 prevented reperfusion injury as compared with TNF-alpha; TNF-alpha increased perivascular interstitial edema and disrupted tissue lattice integrity, whereas IGF-1 maintained myocardial cellular integrity and did not increase edema. Also, there was a significant reduction in detectable creatine phosphokinase in the perfusate from IGF-1 treated hearts. By recording transduced pressures generated during the cardiac cycle, reperfusion with IGF-1 was accompanied by markedly improved cardiac performance as compared with reperfusion with TNF-alpha or modified Kreb's solution only. The histologic and functional improvement generated by IGF-1 was characterized by maintenance of the ratio of mitochondrial to nuclear DNA within heart tissue., Conclusion: We conclude that IGF-1 protects ischemic myocardium from further reperfusion injury, and that this may involve mitochondria-dependent mechanisms.

Published
2003
Full Text
View/download PDF

47. CCR5Delta32 and promoter polymorphisms are not correlated with initial virological or immunological treatment response.

Author

Brumme ZL, Chan KJ, Dong W, Hogg R, O'Shaughnessy MV, Montaner JS, and Harrigan PR

Subjects
Alleles, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Cohort Studies, Gene Frequency, Genotype, HIV Infections immunology, HIV Infections metabolism, HIV Infections virology, Humans, Linkage Disequilibrium, Patient Compliance, Receptors, CCR5 classification, Retrospective Studies, Treatment Outcome, CD4-Positive T-Lymphocytes cytology, HIV Infections drug therapy, Polymorphism, Genetic, Promoter Regions, Genetic, Receptors, CCR5 genetics, Viral Load
Abstract

Objective: Natural genetic polymorphisms within the CCR5 gene and promoter have been linked to patterns of HIV-1 clinical disease progression in untreated individuals. The objective of this retrospective study was to assess the influence of the CCR5Delta32 mutation and promoter polymorphisms on virological and immunological treatment outcome in 436 antiretroviral-naive individuals initiating their first therapy, over a mean follow-up time of 22 months., Methods: Genotypes for the CCR5Delta32 and promoter were determined by polymerase chain reaction amplification of human DNA from plasma, followed by gel electrophoresis for CCR5Delta32 or DNA sequencing for the promoter polymorphisms. Time to virological failure [defined as the second plasma viral load > or = 400 copies HIV-1 RNA/ml) and immunological failure (defined as time to achieve two successive CD4 cell counts below baseline) were analyzed by Kaplan-Meier methods., Results: The five most common CCR5 promoter polymorphisms were observed at positions 208(G/T), 303(A/G), 627(C/T), 676(A/G), and 927(C/T). Allele frequencies were 0.24(208T), 0.38(303G), 0.44(627T), 0.35(676G) and 0.18(927T). The CCR5Delta32 allele frequency was 0.08. The promoter polymorphisms existed in strong linkage disequilibrium with each other and the Delta32. No significant effect of the individual CCR5Delta32 or promoter polymorphisms could be demonstrated with respect to time to treatment failure as defined by virological or immunological parameters (P > or = 0.07). Similarly, when combined CCR5Delta32 and promoter genotypes were analyzed in order to account for linkage disequilibrium, no significant effect was observed on time to virological or immunological failure (P > 0.6)., Conclusion: CCR5Delta32 and promoter genotypes may not be of clinical relevance in predicting initial virological or immunological response to antiretroviral therapy.

Published
2001
Full Text
View/download PDF

48. Human immunodeficiency virus type 1 protease cleavage site mutations associated with protease inhibitor cross-resistance selected by indinavir, ritonavir, and/or saquinavir.

Author

Côté HC, Brumme ZL, and Harrigan PR

Subjects
Amino Acid Sequence, Amino Acid Substitution, Case-Control Studies, Drug Resistance, Microbial, Drug Therapy, Combination, HIV Infections drug therapy, HIV Infections virology, HIV Protease chemistry, HIV Protease metabolism, HIV Protease Inhibitors therapeutic use, HIV-1 enzymology, Humans, Indinavir pharmacology, Indinavir therapeutic use, Molecular Sequence Data, Polymorphism, Genetic, Reverse Transcriptase Inhibitors therapeutic use, Ritonavir pharmacology, Ritonavir therapeutic use, Saquinavir pharmacology, Saquinavir therapeutic use, HIV Protease genetics, HIV Protease Inhibitors pharmacology, HIV-1 drug effects, HIV-1 genetics, Mutation
Abstract

We examined the prevalence of cleavage site mutations, both within and outside the gag region, in 28 protease inhibitor (PI) cross-resistant patients treated with indinavir, ritonavir, and/or saquinavir compared to control patients treated with reverse transcriptase inhibitors. Three human immunodeficiency virus protease cleavage sites within gag (p2/NC, NC/p1, and NC/TFP) showed considerable in vivo evolution before and after therapy with indinavir, ritonavir, and/or saquinavir. Another gag cleavage site (p1/p6(gag)) showed a trend compared to matched controls. The other eight recognized cleavage sites showed relatively little difference between PI-resistant cases and controls. An A-->V substitution at the P2 position of the NC/p1 and NC/TFP cleavage sites was the most common (29%) change selected by the PIs used in this study.

Published
2001
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results