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    8th IAS Conference on HIV Pathogenesis, Treatment and Prevention (IAS 2015).
    Pate, KM ; Pohlmeyer, C ; Walker-Sperling, V ; Foote, J ; Najarro, K ; Cryer, C ; Salgado, M ; Gama, L ; Engle, E ; Shirk, E ; Queen, S ; Chioma, S ; Vermillion, M ; Bullock, B ; Li, M ; Lyons, C ; Adams, R ; Zink, C ; Clements, J ; Mankowski, J ; Blankson, J ; Micci, L ; Ryan, E ; Fromentin, R ; Benne, C ; Chomont, N ; Lifson, J ; Paiardini, M ; Lee, S ; Chomont, N ; Fromentin, R ; Silicano, R ; Silicano, J ; Richman, D ; O'Doherty, U ; Palmer, S ; Burbelo, P ; Deeks, S ; Ghneim, K ; Ahlers, J ; Fourati, S ; Shive, C ; Cameron, M ; Mukerjee, P ; Ghannoum, M ; Rodriguez, B ; Deeks, S ; Lederman, M ; Sekaly, R ; Frange, P ; Faye, A ; Avettand-Fenoel, V ; Bellaton, E ; Deschamps, D ; Angin, M ; Caillat-Zucman, S ; Peytavin, G ; Le Chenadec, J ; Warszawski, J ; Rouzioux, C ; Saez-Cirion, A ; Chang, C ; Cameron, P ; Elliott, J ; Perelson, A ; Roche, M ; Dantanarayana, A ; Solomon, A ; Naranbhai, V ; Tenakoon, S ; Hoh, R ; McMahon, J ; Sikaris, K ; Hartogensis, W ; Bacchetti, P ; Hecht, F ; Lifson, J ; Deeks, S ; Lewin, S ; Byrareddy, S ; Arthos, J ; Cicala, C ; Reimann, K ; Parslow, T ; Santangelo, P ; Villinger, F ; Fauci, A ; Ansari, A ; George, M ; Weiser, B ; Burger, H ; Lewy, T ; Anastos, K ; Asmuth, D ; Somsouk, M ; Hunt, P ; Min, Z ; Miller, C ; Li, XD ; Hinkle, J ; Shaw, A ; Weaver, E ; Klein, G ; Viljoen, K ; Wendoh, J ; Karaoz, U ; Brodie, E ; Mulder, N ; Botha, G ; Kidzeru, E ; Butcher, J ; Gray, C ; Rosenthal, K ; Abimiku, A ; Cameron, B ; Stintzi, A ; Jaspan, H ; Schafer, J ; Evans, T ; Li, H ; Reeves, RK ; Kroon, M ; Dunning, L ; Hsiao, M ; Myer, L ; Crowell, CS ; Maiga, AI ; Sylla, M ; Taiwo, B ; Koné, N ; Murphy, RL ; Marcelin, A-G ; Traore, B ; Fofana, DB ; Chadwick, EG ; Ásbjörnsdóttir, KH ; Slyker, JA ; Wamalwa, D ; De Rosa, S ; Hughes, JP ; Rowhani-Rahbar, A ; Chohan, BH ; Benki-Nugent, S ; Tapia, K ; John-Stewart, GC ; Kizito, H ; Gaur, A ; Prasitsuebsai, W ; Rakhmanina, N ; Chokephaibulkit, K ; Fourie, J ; Bekker, L-G ; Shao, Y ; Bennett, S ; Quirk, E ; Prasitsuebsai, W ; Teeraananchai, S ; Truong, KH ; Ananworanich, J ; Chau, V ; Van Nguyen, L ; Kosalaraksa, ; Kurniati, N ; Sudjaritruk, T ; Chokephaibulkit, K ; Singtoroj, T ; Kerr, SJ ; Sohn, AH ; Lombaard, J ; Bunupuradah, T ; Flynn, P ; Ramapuram, J ; Ssali, F ; Crauwels, H ; Hoogstoel, A ; Van Eygen, V ; Stevens, M ; Boven, K ; Jao, J ; Myer, L ; Phillips, T ; Petro, G ; Zerbe, A ; Abrams, EJ ; Hanrahan, C ; Martinson, N ; Link-Barnes, G ; Msandiwa, R ; Chaisson, R ; Golub, J ; Evans, DH ; Schnippel, K ; Budgell, E ; Shearer, K ; Berhanu, R ; Long, L ; Rosen, S ; Schultze, A ; Efsen, AMW ; Post, FA ; Panteleev, A ; Furrer, H ; Miller, R ; Losso, MH ; Toibaro, J ; Skrahin, A ; Miro, JM ; Caylà, JA ; Girardi, E ; Bruyand, M ; Obel, N ; Podlekareva, DN ; Lundgren, JD ; Mocroft, A ; Kirk, O ; Baddeley, A ; Doherty, M ; Kanchar, A ; Matteelli, A ; Timimi, HB ; Getahun, H ; Hosseinipour, M ; Bisson, G ; Miyahara, S ; Sun, X ; Moses, A ; Riviere, C ; Kirui, FK ; Badal-Faesen, S ; Lagat, D ; Nyirenda, M ; Naidoo, K ; Hakim, J ; Mugyenyi, P ; Henostroza, G ; Leger, PD ; Lama, JR ; Mohapi, L ; Alave, J ; Mave, V ; Veloso, VG ; Pillay, S ; Kumarasamy, N ; Bao, J ; Hogg, E ; Jones, L ; Zolopa, A ; Kumwenda, J ; Gupta, A ; Cohen, M ; Chen, Y ; McCauley, M ; Gamble, T ; Hosseinipour, M ; Kumarasamy, N ; Hakim, J ; Kumwenda, N ; Brum, T ; Grinsztejn, B ; Godbole, S ; Chariyalertsak, S ; Santos, RB ; Mayer, K ; Hoffman, I ; Eshleman, S ; Piwowar-Manning, E ; Ou, S-S ; Cottle, L ; Makhema, J ; Mills, L ; Panchia, R ; Badal-Faesen, S ; Eron, J ; Gallant, J ; Havlir, D ; Swindells, S ; Elharrar, V ; Burns, D ; Taha, T ; Nielsen, K ; Celentano, D ; Essex, M ; Fleming, T ; Jean, K ; Puren, A ; Cutler, E ; Singh, B ; Bouscaillou, J ; Rain-Taljaard, R ; Taljjard, D ; Lissouba, P ; Peytavin, G ; Auvert, B ; Jenkins, L ; Nordio, J ; Vasarhelyi, K ; Nunez, A ; Barrios, R ; Rutherford, A ; Iwuji, C ; Dray-Spira, R ; Calmy, A ; Larmarange, J ; Orne-Gliemann, J ; Dabis, F ; Pillay, D ; Porter, K ; Barnabas, R ; van Rooyen, H ; Tumwesigye, E ; Brantley, J ; Baeten, J ; van Heerden, A ; Turyamureeba, B ; Joseph, P ; Krows, M ; Hughes, J ; Celum, C ; Eshleman, SH ; Hudelson, SE ; Ou, SS ; Redd, AD ; Swanstrom, R ; Porcella, SF ; Chen, YQ ; Piwowar-Manning, E ; McCauley, M ; Gamble, T ; Sievers, M ; Martens, CA ; Bruno, D ; Ping, L-H ; Dukhovlinova, E ; Quinn, TC ; Kumwenda, J ; Maliwichi, M ; Nhando, N ; Akelo, V ; Moyo, S ; Panchia, R ; Kumarasamy, N ; Chotirosniramit, N ; Rocha, MM ; Bustorff, F ; Grinsztejn, B ; Mayer, KH ; Hughes, JP ; Cohen, MS ; Haas, AD ; Tenthani, L ; Msukwa, MT ; Jahn, A ; Midiani, D ; Mhango, E ; Gadabu, O ; Tal, K ; Spörri, A ; Egger, M ; Chimbwandira, F ; van Oosterhout, JJ ; Keiser, O ; Rosenberg, N ; Mtande, T ; Saidi, F ; Stanley, C ; Jere, E ; Mwangomba, L ; Kumwenda, K ; Mofolo, I ; Mwale, M ; Chauma, A ; Miller, WC ; Hoffman, I ; Hosseinipour, MC ; Buzdugan, R ; McCoy, SI ; Watadzaushe, C ; Dufour, M-SK ; Petersen, M ; Dirawo, J ; Mushavi, A ; Mujuru, HA ; Mahomva, A ; Engelsmann, B ; Hakobyan, A ; Mugurungi, O ; Cowan, FM ; Padian, NS ; Lallemant, M ; Amzal, B ; Urien, S ; Sripan, P ; Cressey, T ; Ngo-Giang-Huong, N ; Rawangban, B ; Sabsanong, P ; Siriwachirachai, T ; Jarupanich, T ; Kanjanavikai, P ; Wanasiri, P ; Koetsawang, S ; Jourdain, G ; Le Cœur, S ; Ochoa-Moreno, I ; Mangenah, C ; Buzdugan, R ; Padian, NS ; Mccoy, SI ; Cowan, FM ; Bautista-Arredondo, S ; Wambura, M ; Hayes, R ; Grund, J ; Kapiga, S ; Mahler, H ; Mshana, G ; Kuringe, E ; Plotkin, M ; Bock, N ; Larke, N ; Changalucha, J ; Weiss, H ; Thirumurthy, H ; Akello, I ; Murray, K ; Masters, S ; Maman, S ; Omanga, E ; Agot, K ; Duwve, J ; Hoover, K ; Conrad, C ; Galang, R ; Hillman, D ; Hoots, B ; Patel, M ; Peters, P ; Pontones, P ; Roseberry, J ; Shields, J ; Waterhouse, D ; Weidle, P ; Galang, RR ; Gentry, J ; Peters, PJ ; Blosser, SJ ; Chapman, EL ; Conrad, C ; Duwve, JM ; Ganova-Raeva, L ; Heneine, W ; Hillman, D ; Jia, H ; Liu, L ; Luo, W ; Lovchik, J ; Masciotra, S ; Owen, SM ; Perez, A ; Peyrani, P ; Pontones, P ; Ramachandran, S ; Roseberry, JC ; Sandoval, M ; Shankar, A ; Thai, H ; Xia, G ; Khudyakov, Y ; Switzer, WM ; Mannheimer, S ; Hirsch-Moverman, Y ; Loquere, A ; Franks, J ; Hughes, J ; Ou, S-S ; Amico, KR ; Hendrix, C ; Dye, BJ ; Piwowar-Manning, E ; Marzinke, M ; Elharrar, V ; Stirratt, M ; Grant, RM ; Holtz, TH ; Chitwarakorn, A ; Curlin, ME ; Hughes, J ; Amico, KR ; Hendrix, C ; Dye, BJ ; Anderson, PL ; Ou, S-S ; Elharrar, V ; Eshleman, SH ; Stirratt, M ; Grant, RM ; Doherty, M ; Beusenberg, M ; Asamoah-Odei, E ; Lule, F ; Pendse, R ; Ghidinelli, M ; Lo, Y-R ; Reidner, G ; Donoghoe, M ; Vitoria, M ; Hirnschall, G ; Levi, J ; Raymond, A ; Pozniak, A ; Vernazza, P ; Kohler, P ; Ford, N ; Hill, A ; Wolff, M ; Cortes, CP ; Shepherd, BE ; Giganti, M ; Gowan, CM ; Rawat, A ; Uebel, KE ; Moore, D ; Yassi, A ; Wilkinson, L ; Harley, B ; Jacobs, S ; Cragg, C ; Kriel, E ; Solomon, S ; Peton, N ; Jennings, K ; Youngleson, M ; Grimsrud, A ; Joy, J ; Liang, R ; McCloskey, R ; Nguyen, T ; Brumme, C ; Colley, G ; Hogg, R ; Montaner, J ; Harrigan, PR ; Poon, A ; Klein, K ; Ratcliff, A ; Nickel, G ; Nankya, I ; Lobritz, M ; Gao, Y ; Shattock, R ; Arts, E ; Kinloch, NN ; Macmillan, DR ; Le, AQ ; Cotton, LA ; Mccloskey, R ; Bangsberg, DR ; Buchbinder, S ; Carrington, M ; Fuchs, J ; Harrigan, PR ; Koblin, B ; Markowitz, M ; Mayer, K ; Milloy, MJ ; Schechter, MT ; Wagner, T ; Walker, BD ; Carlson, JM ; Poon, AFY ; Brumme, ZL ; Mesplède, T ; Anstett, K ; Osman, N ; Hassounah, S ; Liang, J ; Han, Y ; Wainberg, M ; Demeulemeester, J ; Vets, S ; Schrijvers, R ; Madlala, P ; De Maeyer, M ; De Rijck, J ; Ndung'u, T ; Debyser, Z ; Gijsbers, R ; Prentice, H ; Tomaras, G ; Geraghty, D ; Apps, R ; Fong, Y ; Ehrenberg, P ; Rolland, M ; Kijak, G ; Nelson, W ; Decamp, A ; Shen, X ; Yates, N ; Zolla-Pazner, S ; Nitayaphan, S ; Rerks-Ngarm, S ; Pitisuttithum, P ; Ferrari, G ; Montefiori, D ; McElrath, J ; Bailer, R ; Koup, R ; O'Connell, R ; Robb, M ; Michael, N ; Kim, J ; Thomas, R ; Peterson, C ; Wang, J ; Polacino, P ; Holmes, M ; Hu, S-L ; Gregory, P ; Kiem, H-P ; Kaminski, R ; Hu, W ; Zhang, Y ; Karn, J ; Khalili, K ; Chew, G ; Fujita, T ; Clayton, K ; Ishii, N ; Abdel-Mohsen, M ; Liegler, T ; Hecht, F ; Ostrowski, M ; Shikuma, C ; Maurer, M ; Korman, A ; Deeks, S ; Ndhlovu, L ; Karn, J ; Das, B ; Dobrowolski, C ; Scully, E ; Deeks, S ; Gandhi, M ; Johnston, R ; Bunupuradah, T ; Kiertiburanakul, S ; Avihingsanon, A ; Chetchotisakd, P ; Techapornroong, M ; Leerattanapetch, N ; Kantipong, P ; Bowonwatanuwong, C ; Banchongkit, S ; Klinbuayaem, V ; Mekviwattanawan, S ; Nimitvilai, S ; Jirajariyavej, S ; Prasithsirikul, W ; Munsakul, W ; Bhakeecheep, S ; Chaivooth, S ; Phanuphak, P ; Cooper, DA ; Apornpong, T ; Kerr, SJ ; Emery, S ; Ruxrungtham, K ; Mills, T ; Andrade, J ; Diperri, G ; Van Lunzen, J ; Koenig, E ; Elion, R ; Cavassini, M ; Madruga, JV ; Brunetta, J ; Shamblaw, D ; Dejesus, E ; Cohen, C ; Plummer, A ; Liu, Y ; McCallister, S ; Gupta, S ; Pozniak, A ; Arribas, J ; Post, F ; Bloch, M ; Gathe, J ; Benson, P ; Custodio, J ; Abram, M ; Wei, X ; Cheng, A ; McCallister, S ; Fordyce, M ; Gatell, J ; Raffi, F ; Plettenberg, A ; Smith, D ; Portilla, J ; Hoffmann, C ; Arasteh, K ; Thompson, M ; Hagins, D ; Morales-Ramirez, J ; Xu, X ; Teppler, H ; Trahan, M-J ; Lamarre, V ; Metras, M-E ; Lapointe, N ; Kakkar, F ; Hwang, C ; Schürmann, D ; Sobotha, C ; Boffito, M ; Sevinsky, H ; Ray, N ; Ravindran, P ; Xiao, H ; Krystal, M ; Dicker, I ; Grasela, D ; Lataillade, M ; Brunet, L ; Moodie, EE ; Young, J ; Walmsley, S ; Hull, M ; Cooper, C ; Klein, MB ; Naggie, S ; Cooper, C ; Saag, M ; Yang, JC ; Stamm, LM ; Pang, PS ; McHutchison, JG ; Dieterich, D ; Sulkowski, MS ; Wyles, D ; Eron, JJ ; Lalezari, J ; Wang, C ; Ruane, PJ ; Blick, G ; Bhatti, L ; Hu, YB ; Co, M ; Gibbons, K ; Trinh, R ; Sulkowski, MS ; Casado, JL ; Bañon, S ; Quereda, C ; Moreno, A ; Elías, MJP ; Moreno, S ; Saeed, S ; Rollet-Kurhajec, K ; Strumpf, EC ; Klein, MB ; Rockstroh, JK ; Nelson, M ; Katlama, C ; Lalezari, J ; Mallolas, J ; Bloch, M ; Matthews, G ; Saag, MS ; Zamor, P ; Orkin, C ; Gress, J ; Shaughnessy, M ; Klopfer, S ; Platt, HL ; Robertson, M ; Sulkowski, M ; Lacombe, K ; Fontaine, H ; Dhiver, C ; Rosenthal, E ; Metivier, S ; Antonini-Michelle, T ; Valantin, MA ; Miailhes, P ; Harent, S ; Batisse, D ; Pageaux, G-P ; Aumaitre, H ; Dominguez, S ; Chas, J ; Allegre, T ; Lafeuillade, A ; De Truchis, P ; De Ledinghen, V ; Leroy, V ; Billaud, E ; Sogni, P ; Dabis, F ; Wittkop, L ; Duvivier, C ; Filipovics, A ; Fedchuk, L ; Bennai, Y ; Salmon, D ; Karim, QA ; Leask, K ; Kharsany, A ; Humphries, H ; Ntombela, F ; Samsunder, N ; Baxter, C ; Frohlich, J ; van der Elst, L ; Karim, SA ; Thirumurthy, H ; Masters, S ; Rao, S ; Murray, K ; Omanga, E ; Agot, K ; Marshall, BDL ; Elston, B ; Dobrer, S ; Montaner, J ; Kerr, T ; Wood, E ; Milloy, M-J ; Czaicki, N ; Njau, P ; Bautista-Arredondo, S ; Simba, O ; Padian, N ; McCoy, S ; Haber, N ; Tanser, F ; Herbst, K ; Pillay, D ; Bärnighausen, T ; Pettifor, A ; MacPhail, C ; Selin, A ; Gomez-Olivé, X ; Hughes, J ; Wagner, R ; Mabuza, W ; Mokoena, I ; Eshleman, S ; Piwowar-Manning, E ; Twine, R ; Julien, A ; Marcus, C ; Andrew, P ; Wang, J ; Xing, Y ; McKinstry, L ; Hamilton, E ; Agyei, Y ; Allison, S ; Sato, P ; Townley, E ; Tollman, S ; Kahn, K ; Solomon, MM ; Schechter, M ; Liu, AY ; McMahan, V ; Guanira, JV ; Hance, RJ ; Chariyalertsak, S ; Mayer, KH ; Grant, RM ; Liu, A ; Cohen, S ; Vittinghoff, E ; Anderson, P ; Doblecki-Lewis, S ; Bacon, O ; Chege, W ; Elion, R ; Buchbinder, S ; Kolber, M ; Henderson, F ; Taylor, A ; Chirwa, L ; Williams, T ; Borkowf, C ; Kasonde, M ; Mutanhaurwa, R ; Matlhaba, O ; Hageman, K ; Casillas, P ; Hosek, S ; Rudy, B ; Landovitz, R ; Kapogiannis, B ; Siberry, G ; Liu, N ; Rutledge, B ; Brothers, J ; Rooney, J ; Wilson, CM ; Hoagland, B ; Veloso, VG ; De Boni, RB ; Madruga, JV ; Kallas, EG ; Fernandes, NM ; Moreira, RI ; Liu, AY ; Grinsztejn, B ; Nair, G ; Justman, JE ; Piper, J ; Marzinke, M ; Hendrix, C ; Dai, J ; Pan, J ; Galaska, B ; Levy, L ; Shwartz, J ; McGowan, I ; Dezutti, C ; Xu, J ; Tang, W ; Zou, H ; Mahapatra, T ; Hu, Q ; Fu, G ; Wang, Z ; Lu, L ; Zhuang, M ; Chen, X ; Fu, J ; Yu, Y ; Lu, J ; Jiang, Y ; Geng, W ; Han, X ; Shang, H ; Wimonsate, W ; Pattanasin, S ; Sriporn, A ; Luechai, P ; Satumay, K ; Tippanonth, N ; Promda, N ; Holtz, T ; Chitwarakorn, A ; Dunne, E ; Chan, G ; Bennett, A ; Buskin, S ; Dombrowski, J ; Golden, M ; Grosso, A ; Stahlman, S ; Mothopeng, T ; Taruberekera, N ; Ouedraogo, G ; Ky-Zerbo, O ; Pitche, V ; Anato, S ; Sithole, B ; Mabuza, X ; Ceesay, N ; Diouf, D ; Trapence, G ; Umar, E ; Baral, S ; Khosropour, CM ; Katz, DA ; Dombrowski, JC ; Golden, MR ; Bavinton, BR ; Jin, F ; Prestage, G ; Zablotska, I ; Grinsztejn, B ; Phanuphak, N ; Friedman, RK ; Grulich, AE ; Sathane, I ; Horth, R ; Boothe, M ; Baltazar, CS ; Young, P ; Fisher, H ; Teodoro, E ; Gouveia, ML ; Lane, T ; Mcfarland, W ; Booth, R ; Davis, J ; Dvoryak, S ; Brewster, J ; Strathdee, S ; Latkin, C ; Joseph, B ; Milloy, MJ ; Nguyen, HH ; Bui, DD ; Dinh, TTT ; Nguyen, MS ; Tran, HT ; Le Hai Nguyen, ; Van Nguyen, TT ; Vu, QD ; Nhan, T ; Le, AKA ; Nguyen, BC ; Suthar, A ; Lo, Y-R ; Pham, HT ; Le, MG ; Nguyen, HL ; Kato, M ; Richardson, L ; Kerr, T ; Hogg, B ; Guillemi, S ; Montaner, J ; Wood, E ; Milloy, M-J ; Cousien, A ; Leclerc, P ; Morissette, C ; Bruneau, J ; Roy, É ; Yazdanpanah, Y ; Cox, J ; Bershteyn, A ; Klein, D ; Oishi, K ; Eckhoff, P ; Leisegang, R ; Mcmahon, J ; Hislop, M ; Stinson, K ; Boulle, A ; Elliott, J ; Maartens, G ; Kim, A ; Nganga, L ; Mukui, I ; Wamicwe, J ; Mwanyumba, S ; Bowen, N ; Wiesner, L ; De Cock, K ; Han, L ; Tang, W ; Best, J ; Zhang, Y ; Kim, J ; Liu, F ; Mollan, K ; Hudgens, M ; Bayus, B ; Terris-Prestholt, F ; Galler, S ; Yang, L ; Peeling, R ; Volberding, P ; Ma, B ; Yang, B ; Huang, S ; Fenton, K ; Wei, C ; Tucker, J ; Dombrowski, JC ; Hughes, JP ; Buskin, SE ; Simoni, JM ; Katz, D ; Fleming, M ; Nunez, A ; Golden, MR ; Schmitz, K ; Scheepers, E ; Okonji, E ; Kawooya, V ; Yotebieng, M ; Thirumurthy, H ; Moracco, KE ; Kawende, B ; Chalachala, JL ; Wenzi, LK ; Ravelomanana, NLR ; Edmonds, A ; Thompson, D ; Okitolonda, E ; Behets, F ; Musarandega, R ; Mahomva, A ; Robinson, J ; Tumbare, E ; Sen, PD ; Hakobyan, A ; Mushavi, A ; Domercant, JW ; Puttkammer, N ; Lu, L ; Francois, K ; Duncan, D ; Grand'Pierre, R ; Lowrance, D ; Adler, M ; Tih, PM ; Katayi, E ; Mboh, E ; Bonje, E ; Lem, E ; Awa, JC ; Lim, JR ; Duncan, D ; Petit, L ; Bianchi, F ; Welty, T ; Achu, MN ; Tayong, G ; Tene, G ; Mosoko, JJ ; Bolu, O ; Kieffer, MP ; Woelk, G ; Mpofu, D ; Cathcart, R ; Okala, SG ; King, DF ; Shattock, RJ ; Jacob, RA ; Moyo, T ; Schomaker, M ; Abrahams, F ; Pujol, BG ; Dorfman, J ; Valenzuela-Ponce, H ; Ávila-Ríos, S ; Garrido-Rodríguez, D ; García-Téllez, T ; Soto-Nava, M ; Escamilla-Gómez, T ; García-Morales, C ; Cortés-Álvarez, J ; Hernández-Juan, R ; Murakami-Ogasawara, A ; Mejía-Villatoro, C ; Pascale, J ; Porras, G ; Quant, C ; Lorenzana, I ; Meza, R ; Palou, E ; Manzanero, M ; Reyes-Terán, G ; Mailiiard, RB ; Smith, KN ; Piazza, P ; Mullins, JI ; Rinaldo, CR ; Planas, D ; Gosselin, A ; Monteiro, P ; Goulet, J-P ; Da Fonseca, S ; Cléret-Buhot, A ; Jenabian, M-A ; Routy, J-P ; Ancuta, P ; Jensen, K ; dela Pena-Ponce, MG ; Piatak, M ; Jacobs, W ; Fennelly, G ; Mollan, K ; Hudgens, M ; Kozlowski, P ; Amedee, A ; Estes, J ; Lifson, J ; Van Rompay, K ; Larsen, M ; De Paris, K ; Malatinkova, E ; De Spiegelaere, W ; Bonczkowski, P ; Kiselinova, M ; Vervisch, K ; Trypsteen, W ; Johnson, M ; Verhofstede, C ; de Looze, D ; Murray, C ; Loes, SK-D ; Vandekerckhove, L ; Fletcher, JLK ; Pinyakorn, S ; de Souza, M ; Akapirat, S ; Trichavaroj, R ; Pankam, T ; Kroon, E ; Colby, D ; Prueksakaew, P ; Suttichom, D ; Kim, JH ; Phanuphak, P ; Phanuphak, N ; Ananworanich, J ; Vandendriessche, A ; Mourez, T ; Lemée, V ; Debab, Y ; Peytavin, G ; Ladner, J ; Caron, F ; Plantier, J-C ; Leporrier, J ; Colby, D ; Phanuphak, N ; Sirivichayakul, S ; Prueksakaew, P ; Saengtawan, P ; Trichavaroj, R ; Crowell, T ; Kim, J ; Ananworanich, J ; Phanuphak, P ; Argento, E ; Duff, P ; Bingham, B ; Nguyen, P ; Strathdee, S ; Shannon, K ; Namey, E ; Perry, B ; Headley, J ; Yao, KA ; Ouattara, M ; Shighata, C ; Ferguson, M ; Lane, T ; Sibanyoni, M ; Manyuchi, A ; Osmand, T ; Marr, A ; Grasso, M ; Isdahl, Z ; Mutanha, N ; Makhubela, P ; Silima, M ; Zuma, N ; Struthers, H ; McIntyre, J ; Rees, H ; Venter, F ; Lancaster, K ; Lungu, T ; Hosseinipour, M ; Chadwick, K ; Dibb, Z ; Go, VF ; Pence, BW ; Powers, KA ; Hoffman, IF ; Miller, WC ; Sedaghat, A ; Karamouzian, M ; Sharifi, H ; Mirzazadeh, A ; Shokoohi, M ; Haghdoost, A ; Schwartz, S ; Lambert, A ; Phaswana-Mafuya, N ; Holland, C ; Kose, Z ; Mcingana, M ; Sweitzer, S ; Baral, S ; Grimsrud, A ; Lesosky, M ; Kalombo, C ; Bekker, L-G ; Myer, L ; Caballero, P ; Da Silva, CM ; Da Cruz, M ; Plazy, M ; ElFarouki, K ; Iwuji, C ; Okesola, N ; Orne-Gliemann, J ; Larmarange, J ; Newell, M-L ; Pillay, D ; Dabis, F ; Dray-Spira, R ; Rebeiro, PF ; Cesar, C ; Shepherd, BE ; De Boni, RB ; Cortés, C ; Rodriguez, F ; Belaunzarán-Zamudio, P ; Pape, JW ; Padgett, D ; Hoces, D ; McGowan, CC ; Cahn, P ; Pilcher, C ; Hatano, H ; Dasgupta, A ; Jones, D ; Torres, S ; Calderon, F ; Ospina-Norvell, C ; Hartogensis, W ; Demicco, E ; Geng, E ; Gandhi, M ; Havlir, D ; Wagner, A ; Njuguna, I ; Mugo, C ; Inwani, I ; Maleche-Obimbo, E ; Sherr, K ; Wamalwa, D ; John-Stewart, G ; Slyker, J ; Bandason, T ; Mchugh, G ; Ferrand, R ; Munyati, S ; Kranzer, K ; Chonzi, P ; Elyanu, P ; Magongo, E ; Asire, B ; Lukabwe, I ; Bitimwine, H ; Katureebe, C ; Achii, P ; Mulema, V ; Dziuban, E ; Sugandhi, N ; Musiime, V ; Namuwenge, N ; Musinguzi, J ; Manno, EC ; Bamford, A ; Conejo, PR ; Marquez, L ; Mellado, MJ ; Muñoz-Fernández, MÁ ; Spoulou, V ; Klein, N ; Ananworanich, J ; Della Negra, M ; Ziegler, JB ; Meanson, E ; Lyall, H ; Shingadia, D ; Di Biagio, A ; Giacomet, V ; Vibeke, R ; de Sousa Marques, HH ; Salo, E ; Volokha, A ; Scherpbier, HJ ; Niehues, T ; Levy, J ; Marczynska, M ; Mardarescu, M ; Reliquet, V ; Giaquinto, C ; Bernardi, S ; Palma, P ; Ronen, K ; Mcgrath, C ; Langat, A ; Kinuthia, J ; Omolo, D ; Singa, B ; Katana, A ; Nganga, L ; John-Stewart, G ; Krebs, E ; Min, JE ; Barrios, R ; Montaner, J ; Nosyk, B ; Kelly, S ; Shattock, A ; Kerr, C ; Stuart, R ; Papoyan, A ; Grigoryan, T ; Hovhannisyan, R ; Grigoryan, S ; Wilson, D ; Rajkotia, Y ; Zang, O ; Nguimkeu, P ; Djurovic, I ; Estill, J ; Ford, N ; Salazar-Vizcaya, L ; Haas, A ; Blaser, N ; Egger, M ; Habiyambere, V ; Keiser, O ; Chuma, B ; Koseki, S ; Musau, S ; Johns, B ; Gatome-Munyua, A ; Honermann, B ; Millett, G ; Lindsey, K ; Wijayaratne, S ; Sherwood, J ; MacAllister, J ; Le, A ; Taylor, J ; Dong, W ; McCloskey, R ; Woods, C ; Hayashi, K ; Milloy, M-J ; Harrigan, PR ; Poon, AF ; Brumme, ZL ; Garrido-Rodriguez, D ; Avila-Rios, S ; Valenzuela-Ponce, H ; García-Tellez, T ; Quiroz-Morales, V ; García-Morales, C ; Soto-Nava, M ; Murakami-Ogasawara, A ; Fernandez-Lopez, JC ; Terán, GR ; Alcami, J ; Bermejo, M ; Descours, B ; Mateos, E ; Lederman, MM ; Benkirane, M ; Coiras, M ; Purcell, D ; Jacobson, J ; Harty, L ; Jarman, K ; Lackovic, K ; Khoury, G ; Mota, T ; Lee, M ; Bernardi, G ; Saleh, S ; Sonza, S ; Lewin, S ; Capoferri, A ; Sievers, M ; Redd, A ; Cash, A ; Xu, D ; Porcella, SF ; Quinn, T ; Siliciano, RF ; Levis, M ; Ambinder, RF ; Durand, CM ; Lee, S-K ; Zhou, S ; Archin, N ; Margolis, D ; Swanstrom, R ; Alcaide, M ; Chisembele, M ; Malupande, E ; Arheart, K ; Jones, D ; Fischl, M ; Vicol, LA ; Hornsberger, A ; Pick, N ; Van Schalkwyk, J ; Bloomenthal, D ; Christilaw, J ; Money, D ; Pyra, M ; Heffron, R ; Mugo, NR ; Nanda, K ; Thomas, KK ; Celum, C ; Kourtis, AP ; Baeten, JM ; Ajibola, G ; Shapiro, R ; Zash, R ; Holmes, L ; Batlang, O ; Ramogothobeng, K ; Chilisa, F ; Bennett, K ; Makhema, J ; Lockman, S ; Powis, K ; Lippman, SA ; Pettifor, AP ; Neilands, TB ; MacPhail, C ; Peacock, D ; Maman, S ; Twine, R ; Selin, A ; Kahn, K ; Derksen, L ; Muula, A ; van Oosterhout, J ; van Lettow, M ; Matengeni, A ; Sodhi, S ; Katz, D ; Golden, M ; Hughes, J ; Farquhar, C ; Stekler, J ; Lippman, SA ; Moran, ME ; Ventura, A ; Castillo, LS ; Buchbinder, S ; Treves-Kagan, S ; Sevelius, JM ; Mavedzenge, SN ; Sibanda, E ; Mavengere, Y ; Hatzold, K ; Mugurungi, O ; Ncube, G ; Cowan, F ; Muffih, PT ; Mboh, E ; Fang, E ; Wainfen, W ; Fon, H ; Welty, T ; Shields, R ; Golden, M ; Bachireddy, C ; Izenberg, J ; Soule, M ; Dvoryak, S ; Altice, F ; Nosyk, B ; Min, JE ; Evans, E ; Li, L ; Liu, L ; Lima, V ; Wood, E ; Montaner, J ; Beletsky, L ; Gonzalez-Zuniga, P ; Rangel, G ; Werb, D ; Arredondo, J ; Strathdee, SA ; Lambdin, BH ; Nyandindi, C ; Bruce, D ; Sabuni, N ; Magimba, A ; Matiko, E ; Milloy, M-J ; Kerr, T ; Hogg, R ; Guillemi, S ; Montaner, J ; Wood, E ; Merlini, E ; Iannuzzi, F ; Bai, F ; Trunfio, M ; Bonora, S ; Calcagno, A ; Cannizzo, ES ; Basilissi, M ; Bini, T ; Monforte, AD ; Marchetti, G ; O'Brien, M ; Manches, O ; Wilen, C ; Wu, V ; Sunseri, N ; Bhardwaj, N ; Bego, MG ; Côté, ÉA ; Aschman, N ; Mercier, J ; Weissenhorn, W ; Cohen, ÉA ; Turrini, F ; Kajaste-Rudnitski, A ; Marelli, SS ; Van Lint, C ; Das, AT ; Berkout, B ; Vicenzi, E ; Simpson, S ; deSilva, T ; Yindom, L-M ; Leligdowicz, A ; Vincent, T ; Rowland-Jones, S ; Webb, GM ; Chew, GM ; Fujita, T ; Burwitz, BJ ; Wu, HL ; Reed, JS ; Hammond, KB ; Hansen, SG ; Maurer, M ; Korman, AJ ; Ndhlovu, LC ; Sacha, JB ; Esser, S ; Geisel, MHM ; Arendt, M ; Schulze, C ; Holzendorf, V ; Warnke, A ; Brockmeyer, NH ; Hower, M ; Schadendorf, D ; Neumann, T ; Eisele, L ; Erbel, R ; Moebus, S ; Jöckel, K-H ; Reinsch, N ; Hamzah, L ; Tiraboschi, JM ; Toby, M ; Iveson, H ; Mant, C ; John, C ; Burling, K ; Kulasegaram, R ; Teague, A ; Post, FA ; Fox, J ; Grant, P ; Kitch, D ; McComsey, G ; Collier, A ; Koletar, S ; Erlandson, K ; Yin, M ; Bartali, B ; Ha, B ; Melbourne, K ; Brown, T ; Sudjaritruk, T ; Bunupuradah, T ; Aurpibul, L ; Kosalaraksa, ; Kurniati, N ; Puthanakit, T ; Spinner, CD ; Kern, KE ; Noe, S ; von Werder, A ; Schwerdtfeger, C ; Schmid, RM ; Zink, A ; Wolf, E ; Iakoubov, R ; Paraskevis, D ; Nikolopoulos, G ; Sypsa, V ; Psichogiou, M ; Malliori, M ; Friedman, SR ; Hatzakis, A ; Thompson, LH ; Wertheim, JO ; Reza, T ; Wylie, JL ; Emmanuel, F ; Brooks, J ; Blanchard, JF ; Sandstrom, P ; Tee, KK ; Kantor, R ; Sungkanuparph, S ; Takebe, Y ; Li, P ; Ditangco, R ; Phanuphak, P ; Sirisanthana, T ; Sim, B ; Ratanasuwan, W ; Kantipong, P ; Mustafa, M ; Merati, TP ; Jiamsakul, A ; Singtoroj, T ; Kamarulzaman, A ; Sulaberidze, L ; Mirzazadeh, A ; Chikovani, I ; Shengelia, N ; Tsereteli, N ; Gotsadze, G ; Mulawa, M ; Reyes, H ; Foshee, V ; Halpern, C ; Kajula, L ; Maman, S ; Treves-Kagan, S ; Ayadi, AE ; Pettifor, A ; MacPhail, C ; Twine, R ; Maman, S ; Kahn, K ; Lippman, SA ; Camlin, CS ; Ssemmondo, E ; Chamie, G ; Kwarisiima, D ; Sang, N ; Bukusi, EA ; Cohen, CR ; Kamya, MR ; Havlir, D ; Schley, A ; Skowronska, E ; Okonji, E ; Scheepers, E ; Feldacker, C ; Myers, S ; Cesar, F ; Parades, Z ; Ferrao, C ; Citao, SC ; Mudender, F ; Golden, M ; Mark, J ; Kinuthia, J ; Osoti, A ; Gone, M ; Asila, V ; Parikh, S ; Krakowiak, D ; Betz, B ; Richardson, B ; Roxby, A ; Farquhar, C ; Pina, C ; Dange, A ; Neytra, S ; Kambli, H ; Karambe, S ; Chhabra, R ; Patel, V ; Ndlovu, B ; Hermanus, T ; Tumba, N ; Moore, P ; Jaggernath, M ; Walker, BD ; Morris, L ; Ndung'u, T ; Leitman, EM ; Hurst, J ; Mori, M ; Matthews, PC ; Frahm, N ; Kublin, J ; Gray, GE ; Goulder, PJ ; Demarco, T ; Rountree, W ; Hora, B ; Chen, Y ; Keinonen, S ; Racz, L ; Daniell, L ; Louzao, R ; Sanchez, A ; Busch, M ; Denny, T ; Gao, F ; Johnson, A ; Jacob, R ; Haeryfar, M ; Dikeakos, J ; Mohammed, T ; Gaseitsiwe, S ; Matlhagela, K ; Matsheka, M ; Moyo, S ; Musonda, R ; Moukambi, F ; Rabezanahary, H ; Rodrigues, V ; Estaquier, J ; Ndjoyi-Mbiguino, A ; Nzengui, GFN ; Kamdem, HM ; Bélec, L ; Viana, R ; Xaba, T ; Stojiljkovic, T ; Gunther, N ; Wallis, C ; Grimsrud, A ; Cornell, M ; Schomaker, M ; Fox, MP ; Orrell, C ; Prozesky, H ; Stinson, K ; Tanser, F ; Egger, M ; Myer, L ; Nsumba, MS ; Barbara, C ; Musomba, RZ ; Kaimal, A ; Ivan, K ; Isaac, L ; Laurence, J ; Rosalind, P-R ; Andrew, K ; Khan, A ; Hans, L ; Gonzales, L ; Carmona, S ; Hsiao, N-Y ; Brophy, J ; Lee, T ; Sauve, L ; Bitnun, A ; Singer, J ; Kakkar, F ; Lapointe, N ; Alimenti, A ; Money, D ; Vaudry, W ; Samson, L ; Singer, J ; Bitnun, A ; Lee, T ; Samson, L ; Brophy, J ; Money, D ; Alimenti, A ; Vaudry, W ; Kakkar, F ; Lapointe, N ; Sauve, L ; du Lou, AD ; Pannetier, J ; Ravalihasy, A ; Gosselin, A ; Supervie, V ; Bajos, N ; Lert, F ; Lydie, N ; Dray-Spira, R ; Kerani, R ; Herbeck, J ; Buskin, S ; Dombrowski, J ; Bennett, A ; Barash, E ; Barbee, L ; Golden, M ; Chang, L ; Grabowski, MK ; Ssekubugu, R ; Nalugoda, F ; Reynolds, S ; Lessler, J ; Moore, S ; Quinn, T ; Gray, R ; Serwadda, D ; Wawer, M ; Ramachandran, A ; Manabe, Y ; Rajasingham, R ; Shah, M ; Schwarz, M ; Flick, R ; Harawa, M ; Simon, K ; Kim, M ; Robison, J ; Ahmed, S ; Schramm, B ; Tayea, A ; Wolters, L ; Nicholas, S ; Masiku, CW ; Zolowere, DB ; Mhango, E ; Kandulu, JR ; Etard, J-F ; Amaros, I ; Szumilin, E ; Gueguen, M ; Ndulue, N ; Etsetowaghan, A ; Gabriel, C ; Ibrahim, J ; Seclen-Palacin, J ; Natumanya, E ; Nabitaka, L ; Bitarakwate, E ; Ismail, S ; Moshgabadi, N ; Galli, R ; Daly, A ; Ko, SMS ; Zhang, M ; Westgard, T ; Bulpitt, A ; Shackleton, CR (Wiley, 2015)
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    2018 international meeting of the Global Virus Network
    Brechot, C ; Bryant, J ; Endtz, H ; Garry, RF ; Griffin, DE ; Lewi, SR ; Mercer, N ; Osterhaus, A ; Picot, V ; Vahlne, A ; Verjans, GMGM ; Weaver, S (ELSEVIER SCIENCE BV, 2019-03)
    The Global Virus Network (GVN) was established in 2011 to strengthen research and responses to emerging viral causes of human disease and to prepare against new viral pandemics. There are now 45 GVN Centers of Excellence and 7 Affiliate laboratories in 29 countries. The 10th International GVN meeting was held from November 28-30, 2018 in Veyrier du Lac, France and was co-hosted by the two GVN Centers of Excellence, the Mérieux Foundation and the University of Veterinary Medicine Hannover (TiHo). The theme of this 10th International GVN meeting was "Eradication and control of (re-) emerging viruses". This report highlights the recent accomplishments of GVN researchers in several important areas of medical virology, including strategies for the eradication of smallpox, measles, polio, SARS and vector-borne or zoonotic infections, emergence and intervention strategies for retroviruses and arboviruses, preparedness for outbreaks of Filo- and other hemophilic viruses, pathogenesis, impact and prevention of respiratory viruses, as well as, viruses affecting the central and peripheral nervous system. Also threats in crisis settings like refugee camps were presented.
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    Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society-Lancet Commission
    Bekker, L-G ; Alleyne, G ; Baral, S ; Cepeda, J ; Daskalakis, D ; Dowdy, D ; Dybul, M ; Eholie, S ; Esom, K ; Garnett, G ; Grimsrud, A ; Hakim, J ; Havlir, D ; Isbell, MT ; Johnson, L ; Kamarulzaman, A ; Kasaie, P ; Kazatchkine, M ; Kilonzo, N ; Klag, M ; Klein, M ; Lewin, SR ; Luo, C ; Makofane, K ; Martin, NK ; Mayer, K ; Millett, G ; Ntusi, N ; Pace, L ; Pike, C ; Piot, P ; Pozniak, A ; Quinn, TC ; Rockstroh, J ; Ratevosian, J ; Ryan, O ; Sippel, S ; Spire, B ; Soucat, A ; Starrs, A ; Strathdee, SA ; Thomson, N ; Vella, S ; Schechter, M ; Vickerman, P ; Weir, B ; Beyrer, C (ELSEVIER SCIENCE INC, 2018-07-28)
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    A new way of measuring apoptosis by absolute quantitation of inter-nucleosomally fragmented genomic DNA
    Hooker, DJ ; Mobarok, M ; Anderson, JL ; Rajasuriar, R ; Gray, LR ; Ellett, AM ; Lewin, SR ; Gorry, PR ; Cherry, CL (OXFORD UNIV PRESS, 2012-08)
    Several critical events of apoptosis occur in the cell nucleus, including inter-nucleosomal DNA fragmentation (apoptotic DNA) and eventual chromatin condensation. The generation of apoptotic DNA has become a biochemical hallmark of apoptosis because it is a late 'point of no return' step in both the extrinsic (cell-death receptor) and intrinsic (mitochondrial) apoptotic pathways. Despite investigators observing apoptotic DNA and understanding its decisive role as a marker of apoptosis for over 20 years, measuring it has proved elusive. We have integrated ligation-mediated PCR and qPCR to design a new way of measuring apoptosis, termed ApoqPCR, which generates an absolute value for the amount (picogram) of apoptotic DNA per cell population. ApoqPCR's advances over current methods include a 1000-fold linear dynamic range yet sensitivity to distinguish subtle low-level changes, measurement with a 3- to 4-log improvement in sample economy, and capacity for archival or longitudinal studies combined with high-throughput capability. We demonstrate ApoqPCR's utility in both in vitro and in vivo contexts. Considering the fundamental role apoptosis has in vertebrate and invertebrate health, growth and disease, the reliable measurement of apoptotic nucleic acid by ApoqPCR will be of value in cell biology studies in basic and applied science.
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    Comparison of HDAC inhibitors in clinical development Effect on HIV production in latently infected cells and T-cell activation
    Rasmussen, TA ; Sogaard, OS ; Brinkmann, C ; Wightman, F ; Lewin, SR ; Melchjorsen, J ; Dinarello, C ; Ostergaard, L ; Tolstrup, M (TAYLOR & FRANCIS INC, 2013-05-01)
    OBJECTIVE: We aimed to compare the potential for inducing HIV production and the effect on T-cell activation of potent HDAC inhibitors undergoing clinical investigation. DESIGN: In vitro study RESULTS: The various HDAC inhibitors displayed significant potency differences in stimulating HIV-1 expression from the latently infected cell lines with panobinostat>givinostat ≈belinostat>vorinostat>valproic acid. Panobinostat was significantly more potent than all other HDAC inhibitors and induced virus production even in the very low concentration range 8-31 nM. The proportion of primary T-cells expressing the early activation marker CD69 increased moderately in all HDAC inhibitor-treated cells compared with untreated cells. Finally, proof was obtained that panobinostat, givinostat and belinostat induce virus production in latently infected primary cells at therapeutic concentrations with panobinostat being the most potent stimulator. METHODS: The latently infected cell lines ACH2 and U1 were treated with the HDAC inhibitors panobinostat, givinostat, belinostat, vorinostat and valproic acid. Viral induction was estimated by p24 production. Peripheral blood mononuclear cells from uninfected donors were treated with the HDAC inhibitors and the expression of activation markers on T-cell phenotypes was measured using flow cytometry. Finally, the ability of givinostat, belinostat and panobinostat to reactivate latent HIV-1 expression in primary T-cells was investigated employing a CCL19-induced latent primary CD4+ T cell infection model. CONCLUSION: At therapeutic concentrations panobinostat stimulate HIV-1 expression in latently infected cells with greater potency than other HDAC inhibitors undergoing clinical investigation. These findings warrant further investigation and panobinostat is now being advanced into clinical testing against latent HIV infection.
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    Limitations of dual-fluorescent HIV reporter viruses in a model of pre-activation latency
    Kim, Y ; Cameron, PU ; Lewin, SR ; Anderson, JL (JOHN WILEY & SONS LTD, 2019-12)
    INTRODUCTION: HIV latency can be established in vitro following direct infection of a resting CD4+ T cell (pre-activation latency) or infection of an activated CD4+ T cell which then returns to a resting state (post-activation latency). We modified a previously published dual-fluorescent reporter virus seeking to track the establishment and reactivation of pre-activation latency in primary CD4+ T cells. METHODS: A previously published dual-fluorescent reporter virus was modified so that expression of enhanced green fluorescent protein (GFP) was under control of the elongation factor 1 alpha (EF1α) promoter to detect latent infection, and E2 crimson (E2CRM) was under control of the nef promoter to detect productive infection. NL4.3 that expressed GFP in place of nef was used as a positive control. We infected the Jurkat T-cell line and primary CD4+ T cells that were either unstimulated or stimulated with either the chemokine CCL19 or phytohaemagglutinin (PHA)/IL-2 and quantified the expression of both fluorescent proteins by flow cytometry. The study was carried out over a period of two years from September 2016 to October 2018. RESULTS AND DISCUSSION: Expression of both fluorophores was detected following infection of the Jurkat T-cell line while only low levels of the latent reporter were observed following infection of primary CD4+ T cells. In unstimulated and CCL19-treated CD4+ T cells, expression of the GFP latent reporter, increased after further activation of the cells with PHA/phorbol 12-myristate 13-acetate (PMA). CONCLUSIONS: Our findings demonstrate that the EF1α promoter has poor constitutive expression in resting CD4+ T cells. Therefore, dual-fluorescent reporter viruses with the EF1α promoter may underestimate the frequency of latent infection in resting CD4+ T cells.
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    Shocking HIV out of hiding: where are we with clinical trials of latency reversing agents?
    Rasmussen, TA ; Lewin, SR (LIPPINCOTT WILLIAMS & WILKINS, 2016-07)
    PURPOSE OF REVIEW: To provide an overview of the initial experiences with the use of latency-reversing agents (LRAs) in clinical trials in HIV and to discuss and contrast results arising from these studies. RECENT FINDINGS: Although the clinical administration of histone deacetylase inhibitors (HDACis) and disulfiram to HIV-infected individuals on antiretroviral therapy significantly increased cell-associated HIV RNA in CD4 T cells and in some cases plasma HIV RNA, this did not reduce the frequency of latently infected cells in blood. Potential reasons for this include insufficient potency in latency reversal, lack of virus or immune-mediated cytolysis of virus-expressing cells and/or a high frequency of immune escape mutations in the recently activated virus. Analyses of HIV-specific T-cell responses in vivo did not demonstrate that HDACis impair immune cell effector functions. SUMMARY: More effective latency-reversing interventions and additional strategies to eliminate virus-expressing cells are needed. Key challenges include testing combinations of LRAs and/or LRAs with immune modulation to optimize potency in the absence of adverse events. A better understanding of the mechanisms of action of LRAs as well as strategies to enhance potency and penetration in tissue are key challenges for future studies.
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    Ethics of ART interruption after stem-cell transplantation
    Sugarman, J ; Lewin, SR ; Henrich, TJ ; Rasmussen, TA (ELSEVIER INC, 2016-01-01)
    In the wake of reports of an HIV cure for Timothy Brown (the Berlin patient) after two haemopoietic stem cell transplantations (HSCT) from a donor homozygous for the CCR5Δ32 mutation, at least four other individuals have had antiretroviral therapy (ART) stopped as analytical treatment interruptions after similar procedures. Only one of those patients received stem cells from a donor homozygous for CCR5Δ32, and three of the recipients were heterozygous for CCR5Δ32. The clinical outcome after each of these interruptions has been disappointing, with pronounced viral rebound and associated morbidity. What if remission among a minority of patients is possible after HSCT, such as that experienced by some patients after treatment during acute infection? 3 Given such discouraging outcomes so far, can analytical treatment interruptions after HSCT be ethically appropriate? This is a crucially important issue, because many patients with HIV will have HSCT, with or without a donor homozygous for CCR5Δ32, and efforts continue to optimise the possibility of using the procedure to achieve HIV remission.
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    Barriers and strategies to achieve a cure for HIV
    Pitman, MC ; Lau, JSY ; McMahon, JH ; Lewin, SR (ELSEVIER INC, 2018-06)
    9 years since the report of a cure for HIV after C-C chemokine receptor type 5 Δ32 stem cell transplantation, no other case of HIV cure has been reported, despite much research. However, substantial progress has been made in understanding the biology of the latent HIV reservoir, and in measuring the amount of virus that persists after antiretroviral therapy (ART) with increasingly sophisticated approaches. This knowledge is being translated into a long pipeline of clinical trials seeking to reduce viral persistence in participants on suppressive treatment and ultimately to allow safe cessation of ART. In this Review, we discuss the main barriers preventing the development of an HIV cure, methods used to measure HIV persistence in individuals on ART, clinical strategies that aim to cure HIV, and future directions for studies in the field of HIV cure research.
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    Toxicity and in vitro activity of HIV-1 latency-reversing agents in primary CNS cells
    Gray, LR ; On, H ; Roberts, E ; Lu, HK ; Moso, MA ; Raison, JA ; Papaioannou, C ; Cheng, W-J ; Ellett, AM ; Jacobson, JC ; Purcell, DFJ ; Wesselingh, SL ; Gorry, PR ; Lewin, SR ; Churchill, MJ (SPRINGER, 2016-08)
    Despite the success of combination antiretroviral therapy (cART), HIV persists in long lived latently infected cells in the blood and tissue, and treatment is required lifelong. Recent clinical studies have trialed latency-reversing agents (LRA) as a method to eliminate latently infected cells; however, the effects of LRA on the central nervous system (CNS), a well-known site of virus persistence on cART, are unknown. In this study, we evaluated the toxicity and potency of a panel of commonly used and well-known LRA (panobinostat, romidepsin, vorinostat, chaetocin, disulfiram, hexamethylene bisacetamide [HMBA], and JQ-1) in primary fetal astrocytes (PFA) as well as monocyte-derived macrophages as a cellular model for brain perivascular macrophages. We show that most LRA are non-toxic in these cells at therapeutic concentrations. Additionally, romidepsin, JQ-1, and panobinostat were the most potent at inducing viral transcription, with greater magnitude observed in PFA. In contrast, vorinostat, chaetocin, disulfiram, and HMBA all demonstrated little or no induction of viral transcription. Together, these data suggest that some LRA could potentially activate transcription in latently infected cells in the CNS. We recommend that future trials of LRA also examine the effects of these agents on the CNS via examination of cerebrospinal fluid.