129 results on '"Gisslen M"'
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2. Highlights of the Global HIV-1 CSF Escape Consortium Meeting, 9 June 2016, Bethesda, MD, USA.
- Author
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Price, Richard, Joseph, J, Cinque, P, Colosi, D, Dravid, A, Ene, L, Fox, H, Gabuzda, D, Gisslen, M, Beth, S, and Letendre, S
- Abstract
CSF HIV escape is a recently recognised phenomenon that suggests that despite suppressive treatment, HIV RNA may be detected in the CNS compartment in some individuals. In rare cases this is associated with clinical neurological disease, while in most case
- Published
- 2016
3. Cerebrospinal Fluid HIV Escape from Antiretroviral Therapy
- Author
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Ferretti, F, Gisslen, M, Cinque, P, and Price, RW
- Subjects
Virology ,Immunology ,Medical Microbiology - Abstract
CNS infection is a nearly constant facet of systemic CNS infection and is generally well controlled by suppressive systemic antiretroviral therapy (ART). However, there are instances when HIV can be detected in the cerebrospinal fluid (CSF) despite suppression of plasma viruses below the clinical limits of measurement. We review three types of CSF viral escape: asymptomatic, neuro-symptomatic, and secondary. The first, asymptomatic CSF escape, is seemingly benign and characterized by lack of discernable neurological deterioration or subsequent CNS disease progression. Neuro-symptomatic CSF escape is an uncommon, but important, entity characterized by new or progressive CNS disease that is critical to recognize clinically because of its management implications. Finally, secondary CSF escape, which may be even more uncommon, is defined by an increase of CSF HIV replication in association with a concomitant non-HIV infection, as a consequence of the local inflammatory response. Understanding these CSF escape settings not only is important for clinical diagnosis and management but also may provide insight into the CNS HIV reservoir.
- Published
- 2015
4. Efficacy and safety of switching from boosted protease inhibitors plus emtricitabine and tenofovir disoproxil fumarate regimens to single-tablet darunavir, cobicistat, emtricitabine, and tenofovir alafenamide at 48 weeks in adults with virologically suppressed HIV-1 (EMERALD): a phase 3, randomised, non-inferiority trial
- Author
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Ajana, F, Arribas, JR, Bailey, J, Benson, P, Berenguer, J, Bhatti, L, Blaxhult, A, Brar, I, Bredeek, UF, Brinson, C, Brunetta, J, Casado, J, Clarke, A, Conway, B, Cotte, L, Crofoot, G, Cunningham, D, de Vente, J, De Wit, S, DeJesus, E, Dietz, C, Dretler, R, Eron, J, Fehr, J, Felizarta, F, Fichtenbaum, C, Flamholc, L, Florence, E, Galindo, MJ, Gallant, J, Gasiorowski, J, Gatell, JM, Gathe, J, Gazzard, BG, Girard, P-M, Gisslèn, M, Gutierrez, F, Gutierrez, MDM, Hagins, D, Halota, W, Henn, S, Henry, WK, Horban, A, Huhn, G, Iribarren, JA, Jain, M, Johnson, MA, Katlama, C, Klein, M, Knobel, H, Lucasti, C, Martorell, C, McDonald, C, Mills, A, Molina, J-M, Morales-Ramirez, J, Mounzer, K, Moutschen, M, Murphy, D, Nahass, R, Negredo, E, Olivet, H, Orkin, C, Osiyemi, O, Perez-Valero, I, Piekarska, A, Pineda, JA, Podzamczer, D, Poizot-Martin, I, Portilla Sogorb, J, Post, F, Prelutsky, D, Pulido, F, Rachlis, A, Raffi, F, Ramgopal, M, Rashbaum, B, Rauch, A, Rey, D, Reynes, J, Ricart, C, Richmond, G, Rivero, A, Ruane, P, Gil, I Santos, Scarsella, A, Scribner, A, Shafran, S, Shalit, P, Shamblaw, D, Slim, J, Stoeckle, M, Tashima, K, Teicher, E, Thalme, A, Ustianowski, A, Van Wijngaerden, E, Vandekerckhove, L, Vandercam, B, Voskuhl, G, Walmsley, S, Ward, D, Waters, L, Wilkin, A, Witor, A, Yazdanpanah, Y, Orkin, Chloe, Molina, Jean-Michel, Negredo, Eugenia, Arribas, José R, Gathe, Joseph, Eron, Joseph J, Van Landuyt, Erika, Lathouwers, Erkki, Hufkens, Veerle, Petrovic, Romana, Vanveggel, Simon, and Opsomer, Magda
- Published
- 2018
- Full Text
- View/download PDF
5. Unbiased serology reveals autoimmunity and HIV antibody signatures in HIV CNS Escape
- Author
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Hawes, I.A., primary, Alvarenga, B.D., additional, Browne, W., additional, Wapniarski, A., additional, Dandekar, R., additional, Bartley, C.M., additional, Sowa, G.M., additional, DeRisi, J.L., additional, Cinque, P., additional, Dravid, A.N., additional, Pleasure, S.J., additional, Gisslen, M., additional, Price, R.W., additional, and Wilson, M.R., additional
- Published
- 2022
- Full Text
- View/download PDF
6. Human immunodeficiency virus continuum of care in 11 european union countries at the end of 2016 overall and by key population: Have we made progress?
- Author
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Vourli, G, Noori, T, Pharris, A, Porter, K, Axelsson, M, Begovac, J, Cazein, F, Costagliola, D, Cowan, S, Croxford, S, Monforte, A, Delpech, V, Diaz, A, Girardi, E, Gunsenheimer-Bartmeyer, B, Hernando, V, Leierer, G, Lot, F, Nunez, O, Obel, N, Op de Coul, E, Paraskeva, D, Patrinos, S, Reiss, P, Schmid, D, Sonnerborg, A, Suligoi, B, Supervie, V, van Sighem, A, Zangerle, R, Touloumi, G, Egle, A, Kanatschnig, M, Ollinger, A, Rieger, A, Schmied, B, Wallner, E, Dewasurendra, D, Gisinger, M, Kitchen, M, Plattner, A, Rieser, E, Sarcletti, M, Greil, R, Schachner, M, Skocic, M, Muller, M, Aichwalder, R, Chromy, D, Grabmeier-Pfstershammer, K, Skoll, M, Touzeau, V, Cichon, P, Wolf-Nussmuller, S, Laferl, H, Zoufaly, A, Genger-Hackl, C, Kapper, A, Schneeberger, T, Trattner, E, Schober, G, Atzl, M, Hartmann, B, Puchhammer-Stockl, E, Berg, J, Appoyer, H, Rappold, M, Strickner, S, Schindelwig, K, Ledergerber, B, Fatkenheuer, G, Gerstof, J, Kronborg, G, Pedersen, C, Larsen, C, Pedersen, G, Mohey, R, Nielsen, L, Weise, L, Kvinesdal, B, Jensen, J, Abgrall, S, Bernard, L, Billaud, E, Boue, F, Boyer, L, Cabie, A, Caby, F, Canestri, A, Cotte, L, de Truchis, P, Duval, X, Duvivier, C, Enel, P, Fischer, H, Gasnault, J, Gaud, C, Grabar, S, Khuong-Josses, M, Launay, O, Marchand, L, Mary-Krause, M, Matheron, S, Melica-Gregoire, G, Melliez, H, Meynard, J, Nacher, M, Pavie, J, Piroth, L, Poizot-Martin, I, Pradier, C, Reynes, J, Rouveix, E, Simon, A, Slama, L, Tattevin, P, Tissot-Dupont, H, Biga, J, Kurth, T, Jacquemet, N, Guiguet, M, Leclercq, S, Lievre, L, Marshall, E, Roul, H, Selinger-Leneman, H, Potard, V, Benveniste, O, Breton, G, Lupin, C, Bourzam, E, Girard, P, Fonquernie, L, Valin, N, Lefebvre, B, Sebire, M, Pialoux, G, Lebrette, M, Tibaut, P, Adda, A, Hamidi, M, Cadranel, J, Lavole, A, Parrot, A, Bouchaud, O, Vignier, N, Mechai, F, Makhlouf, S, Honore, P, Bergmann, J, Delcey, V, Lopes, A, Sellier, P, Parrinello, M, Oksenhendler, E, Gerard, L, Molina, J, Rozenbaum, W, Denis, B, De Castro, N, Lascoux, C, Yazdanpanah, Y, Lariven, S, Joly, V, Rioux, C, Poupard, M, Taverne, B, Sutton, L, Masse, V, Genet, P, Wifaq, B, Gerbe, J, Grefe, S, Dupont, C, Freire Maresca, A, Reimann, E, Bloch, M, Meier, F, Mortier, E, Zeng, F, Montoya, B, Perronne, C, Mathez, D, Marigot-Outtandy, D, Berthe, H, Greder Belan, A, Terby, A, Godin Collet, C, Marque Juillet, S, Ruquet, M, Roussin-Bretagne, S, Colardelle, P, Granier, F, Laurichesse, J, Perronne, V, Akpan, T, Marcou, M, Daneluzzi, V, Veyssier-Belot, C, Masson, H, Welker, Y, Brazille, P, Kahn, J, Zucman, D, Majerholc, C, Fourn, E, Bornarel, D, Chambrin, V, Kansau, I, Raho-Moussa, M, Lelievre, J, Saidani, M, Chesnel, C, Dumont, C, Vittecoq, D, Derradji, O, Bolliot, C, Goujard, C, Teicher, E, Mole, M, Bourdic, K, Salmon, D, Le Jeunne, C, Guet, P, Pietri, M, Pannier Metzger, E, Marcou, V, Loulergue, P, Dupin, N, Morini, J, Deleuze, J, Gerhardt, P, Chanal, J, Weiss, L, Lucas, M, Jung, C, Ptak, M, Viard, J, Ghosn, J, Gazalet, P, Cros, A, Maignan, A, Lortholary, O, Rouzaud, C, Touam, F, Benhadj, K, Consigny, P, Bossi, P, Gergely, A, Cessot, G, Durand, F, Beck-Wirth, G, Michel, C, Benomar, M, Rey, D, Partisani, M, Cheneau, C, Batard, M, Fischer, P, Leclercq, P, Blanc, M, Morand, P, Epaulard, O, Signori-Schmuck, A, Laurichesse, H, Jacomet, C, Vidal, M, Coban, D, Casanova, S, Fresard, A, Guglielminotti, C, Botelho-Nevers, E, Brunon-Gagneux, A, Ronat, V, Verdon, R, Dargere, S, Haustraete, E, Feret, P, Goubin, P, Chavanet, P, Fillion, A, Croisier, D, Gohier, S, Arvieux, C, Souala, F, Chapplain, J, Ratajczak, M, Rohan, J, Faller, J, Ruyer, O, Gendrin, V, Toko, L, Chirouze, C, Hustache-Mathieu, L, Faucher, J, Proust, A, Magy-Bertrand, N, Gil, H, Meaux-Ruault, N, Sotto, A, Rouanet, I, Mauboussin, J, Doncesco, R, Jacques, G, May, T, Rabaud, C, Andre, M, Delestan, M, Bouillon, M, Bani-Sadr, F, Rouger, C, Berger, J, Nguyen, Y, Marchou, B, Delobel, P, Martin Blondel, G, Cuzin, L, Biezunski, N, Alric, L, Bonnet, D, Guivarch, M, Palacin, A, Payssan, V, Ajana, F, Meybeck, A, Viget, N, Pugliese, P, Roger, P, Rosenthal, E, Durant, J, Cua, E, Naqvi, A, Perbost, I, Risso, K, Quinsat, D, Raphael, S, Del Giudice, P, Dides, P, Sambuc, R, Antolini-Bouvenot, M, Druart, P, Meddeb, L, Ravaux, I, Menard, A, Tomei, C, Dhiver, C, Moreau, J, Mokhtari, S, Soavi, M, Tomas, V, Bregigeon, S, Faucher, O, Obry-Roguet, V, Ritleng, A, Petit, N, Bartoli, C, Ruiz, J, Blanc, D, Allegre, T, Sordage, M, Riou, J, Faudon, C, Slama, B, Zerazhi, H, Boulat, O, Chebrek, S, Beyrne, M, Granet Brunello, P, Pellissier, L, Bonnabel, D, Cohen Valensi, R, Mouchet, B, Mboungou, G, Lafeuillade, A, Hope-Rapp, E, Hittinger, G, Philip, G, Lambry, V, Raf, F, Allavena, C, Hall, N, Reliquet, V, Chidiac, C, Ferry, T, Perpoint, T, Miailhes, P, Boibieux, A, Livrozet, J, Makhlouf, D, Brunel, F, Chiarello, P, Hoen, B, Lamaury, I, Fabre, I, Samar, K, Duvallon, E, Clavel, C, Stegmann, S, Walter, V, Adriouch, L, Huber, F, Vanticlke, V, Couppie, P, Abel, S, Pierre-Francois, S, Ricaud, C, Rodet, R, Wartel, G, Sautron, C, Poubeau, P, Borgherini, G, Camuset, G, Arasteh, K, Kowohl Vivantes, S, Schurmann, D, Warncke Charite, M, Rockstroh, J, Wasmuth, J, Hass, S, Jensen, B, Feind, C, Esser, S, Schenk-Westkamp, P, Haberl, A, Stephan, C, Plettenberg, A, Kuhlendahl, F, Adam, A, Weitner, L, Schewe, K, Goey, H, Fenske, S, Buhk, T, Stellbrink, H, Hofmann, C, Hansen, S, Degen, O, Heuer, M, Stoll, M, Gerschmann, S, Horst, H, Trautmann, S, Gillor, D, Bogner, J, Sonntag, B, Salzberger, B, Fritzsche, C, Adamis, G, Antoniadou, A, Chini, M, Chrysos, G, Gikas, A, Gogos, H, Katsarou, O, Lazanas, M, Metallidis, S, Panagopoulos, P, Paparizos, V, Papastamopoulos, V, Paraskevis, D, Psychogiou, M, Sambatakou, H, Sipsas, N, Pantazis, N, Papadopoulos, A, Nitsotolis, T, Xylomenos, G, Marangos, M, Kouramba, A, Kontos, A, Lioni, A, Tsachouridou, O, Kourkounti, S, Ganitis, A, Barbounakis, E, d'Arminio Monforte, A, Antinori, A, Andreoni, M, Castagna, A, Castelli, F, Cauda, R, Di Perri, G, Galli, M, Iardino, R, Ippolito, G, Lazzarin, A, Marchetti, G, Rezza, G, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Cozzi-Lepri, A, Lo Caputo, S, Mussini, C, Puoti, M, Perno, C, Bai, F, Balotta, C, Bandera, A, Bonora, S, Borderi, M, Calcagno, A, Capetti, A, Capobianchi, M, Cicalini, S, Cingolani, A, Cinque, P, Di Biagio, A, Gianotti, N, Gori, A, Guaraldi, G, Lapadula, G, Lichtner, M, Madeddu, G, Maggiolo, F, Monno, L, Nozza, S, Pinnetti, C, Quiros Roldan, E, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Sarmati, L, Fanti, I, Galli, L, Lorenzini, P, Rodano, A, Macchia, M, Tavelli, A, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petroni, F, Prota, G, Trufa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Milano, E, Suardi, C, Donati, V, Verucchi, G, Castelnuovo, F, Minardi, C, Menzaghi, B, Abeli, C, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolf, L, Segala, D, Blanc, P, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Fondaco, L, Bonfanti, P, Molteni, C, Chiodera, A, Milini, P, Nunnari, G, Pellicano, G, Rizzardini, G, Cannizzo, E, Moioli, M, Piolini, R, Bernacchia, D, Salpietro, S, Tincati, C, Puzzolante, C, Migliorino, C, Sangiovanni, V, Borgia, G, Esposito, V, Di Flumeri, G, Gentile, I, Rizzo, V, Cattelan, A, Marinello, S, Cascio, A, Trizzino, M, Francisci, D, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, M, Cristaudo, A, Vullo, V, Acinapura, R, Moschese, D, Capozzi, M, Mondi, A, Rivano Capparuccia, M, Iaiani, G, Latini, A, Gagliardini, R, Plazzi, M, De Girolamo, G, Vergori, A, Cecchetto, M, Viviani, F, De Vito, A, Rossetti, B, Montagnani, F, Franco, A, Fontana Del Vecchio, R, Di Giuli, C, Caramello, P, Orofno, G, Sciandra, M, Bassetti, M, Londero, A, Manfrin, V, Battagin, G, Starnini, G, Ialungo, A, van der Valk, M, Geerlings, S, Goorhuis, A, Hovius, J, Lempkes, B, Nellen, F, van der Poll, T, Prins, J, van Vugt, M, Wiersinga, W, Wit, F, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A, Pijnappel, F, Smalhout, S, Weijsenfeld, A, Jurriaans, S, Back, N, Zaaijer, H, Berkhout, B, Cornelissen, M, Schinkel, C, Wolthers, K, Peters, E, van Agtmael, M, Bomers, M, Sigalof, K, Heitmuller, M, Laan, L, Ang, C, van Houdt, R, Jonges, M, van Prehn, J, Kuijpers, T, Pajkrt, D, Scherpbier, H, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Loof, L, Wintermans, B, Veenemans, J, Pronk, M, Ammerlaan, H, de Munnik, E, Jansz, A, Tjhie, J, Wegdam, M, Deiman, B, Scharnhorst, V, van Eeden, A, Brokking, W, Elsenburg, L, Nobel, H, Damen, M, van Kasteren, M, Berrevoets, M, Brouwer, A, Adams, A, de Kruijf-Van de Wiel, B, Keelan-Pfaf, S, van der Ven, B, Buiting, A, Murck, J, Versteeg, D, de Vries-Sluijs, T, Bax, H, van Gorp, E, Nouwen, J, Rijnders, B, Schurink, C, Verbon, A, de Jong-Peltenburg, N, Bassant, N, van Beek, J, Vriesde, M, van Zonneveld, L, van den Berg-Cameron, H, de Groot, J, Boucher, C, Koopmans, M, van Kampen, J, Fraaij, P, van Rossum, A, Vermont, C, van der Knaap, L, Visser, E, Branger, J, Douma, R, Duijf-Van de Ven, C, Schippers, E, van Nieuwkoop, C, van IJperen, J, Geilings, J, van der Hut, G, van Burgel, N, Leyten, E, Gelinck, L, Mollema, F, Davids-Veldhuis, S, Wildenbeest, G, Heikens, E, Groeneveld, P, Bouwhuis, J, Lammers, A, Kraan, S, van Hulzen, A, Kruiper, M, van der Bliek, G, Bor, P, Bloembergen, P, Wolfagen, M, Ruijs, G, Kroon, F, de Boer, M, Scheper, H, Jolink, H, Dorama, W, van Holten, N, Claas, E, Wessels, E, den Hollander, J, El Moussaoui, R, Pogany, K, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I, Havenith, T, Weijer, S, van Vonderen, M, Kampschreur, L, Faber, S, Steeman-Bouma, R, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F, Cohen Stuart, J, Jansen, E, Hoogewerf, M, Rozemeijer, W, van der Reijden, W, Sinnige, J, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Vrouenraets, S, Brouwer, C, Geerders, G, Hoeksema, K, Kleene, M, Knapen, M, van der Meche, I, Mulder-Seeleman, E, Toonen, A, Wijnands, S, Kwa, D, van Crevel, R, van Aerde, K, Doferhof, A, Henriet, S, ter Hofstede, H, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F, Burger, D, Gisolf, E, Hassing, R, Claassen, M, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, van der Prijt, L, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B, Veenendaal, D, Verhagen, D, Lauw, F, van Broekhuizen, M, van Wijk, M, Bierman, W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Scholvinck, E, Stienstra, Y, Verhage, A, Wouthuyzen-Bakker, K, Boonstra, A, de Groot-De Jonge, H, van der Meulen, P, de Weerd, D, Niesters, H, van Leer-Buter, C, Knoester, M, Hoepelman, A, Arends, J, Barth, R, Bruns, A, Ellerbroek, P, Mudrikova, T, Oosterheert, J, de Regt, M, Schadd, E, van Zoelen, M, Aarsman, K, Grifoen-Van Santen, B, de Kroon, I, van Rooijen, C, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Bont, L, Geelen, S, Loefen, Y, Wolfs, T, Nauta, N, Zaheri, S, Boyd, A, Bezemer, D, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Bretin, N, Djoechro, E, Geerlinks, J, Kruijne, E, Lodewijk, C, Lucas, E, van der Meer, R, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnorr, P, Tuijn, E, Veenenberg, L, Witte, E, Tuk, B, Moreno, S, del Amo, J, Dalmau, D, Navarro, M, Gonzalez, M, Blanco, J, Garcia, F, Rubio, R, Iribarren, J, Gutierrez, F, Vidal, F, Berenguer, J, Gonzalez, J, Sobrino, P, Alejos, B, Alvarez, D, Jarrin, I, Moreno, C, Munoz-Fernandez, M, Garcia-Merino, I, Rico, C, de la Fuente, J, Torre, A, Portilla, J, Merino, E, Reus, S, Boix, V, Giner, L, Gadea, C, Portilla, I, Pampliega, M, Diez, M, Rodriguez, J, Sanchez-Paya, J, Podzamczer, D, Imaz, E, Van Den Eyncle, E, Di Yacovo, S, Sumoy, M, Gomez, J, Hernandez, J, Aleman, M, Alonso, M, Hernandez, M, Diaz-Flores, F, Garcia, D, Pelazas, R, Asensi, V, Valle, E, Carton, J, Perez, V, Molina, M, Garcia, J, Carrera, E, Pulido, F, Bisbal, O, Matarranz, M, Lagarde, M, Rubio-Martin, R, Hernando, A, Bermejo, L, Dominguez, L, Arrizabalaga, J, Aramburu, M, Camino, X, Rodriguez-Arrondo, F, von Wichmann, M, Tome, L, Goenaga, M, Bustinduy, M, Galparsoro, H, Ibarguren, M, Aguado, M, Umerez, M, Masia, M, Lopez, C, Padilla, S, Navarro, A, Montolio, F, Robledano, C, Colome, J, Adsuar, A, Pascual, R, Carlos, F, Martinez, M, Fernandez, M, Garcia, E, Muga, R, Tor, J, Sanvisens, A, Bernaldo de Quiros Lopez, J, Miralles, P, Gutierrez, I, Ramirez, M, Padilla, B, Gijon, P, Carrero, A, Aldamiz-Echevarria, T, Tejerina, F, Parras, F, Balsalobre, P, Diez, C, Peraire, J, Vilades, C, Veloso, S, Vargas, M, Lopez-Dupla, M, Olona, M, Aguilar, A, Sirvent, J, Alba, V, Calavia, O, Montero, M, Lacruz, J, Blanes, M, Calabuig, E, Cuellar, S, Lopez, J, Salavert, M, de la Serna, I, Arribas, J, Montes, M, Pena, J, Arribas, B, Castro, J, Zamora, J, Perez, I, Estebanez, M, Garcia, S, Diaz, M, Alcariz, N, Mingorance, J, Montero, D, Gonzalez, A, Isabel de Jose, M, de los Santos, I, Sanz, J, Salas, A, Sarria, C, Berrocal, A, Garcia-Fraile, L, Oteo, J, Ibarra, V, Metola, L, Sanz, M, Perez-Martinez, L, Pascual, A, Ramos, C, Arazo, P, Gil, D, Jaen, A, Cairo, M, Irigoyen, D, Jordano, Q, Xercavins, M, Martinez-Lacasa, J, Velli, P, Font, R, Sanmarti, M, Ibanez, L, Rivero, M, Casado, M, Diaz, J, Uriz, J, Reparaz, J, Irigoyen, C, Arraiza, M, Segura, F, Amengual, M, Navarro, G, Sala, M, Cervantes, M, Pineda, V, Segura, V, 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P., Lopez D., Gutierrez C., Madrid N., Lamas A., Marti P., de Diaz A., Serrrano S., Donat L., Cano A., Bernal E., Munoz A., Pena A., Munoz L., Parra J., Alvarez M., Chueca N., Guillot V., Vinuesa D., Fernandez J. A., Del Romero J., Rodriguez C., Puerta T., Carrio J. C., Vera M., Ballesteros J., Domingo P., Sambeat M. A., Lamarca K., Mateo G., Gutierrez M., Fernandez I., Antela A., Losada E., Riera M., Penaranda M., Leyes M., Ribas M. A., Campins A. A., Vidal C., Gil L., Fanjul F., Marinescu C., Ribera E., Santos J., Marquez M., Viciana I., Palacios R., Gonzalez C. M., Viciana P., Leal M., Lopez-Cortes L. F., Espinosa N., Munoz J., Zubero M. Z., Baraia-Etxaburu J. M., Ibarra S., Ferrero O., Lopez de Munain J., Camara M. M., Lopez I., de la Pena M., Suarez-Garcia I., Malmierca E., Olalla J., del Arco A., de la Torre J., Prada J. L., Caracuel Z., Lopez-Lirola A. M., Lozano A. B., Fernandez E., Fernandez J. M., Martinez O. J., Vera F. J., Martinez L., Garcia J., Alcaraz B., Jimeno A., Poveda E., Pernas B., Mena A., Grandal M., Castro A., Pedreira J. D., Galera C., Albendin H., Iborra A., Campillo M. A., Vidal A., Amador C., Pasquau F., Ena J., Benito C., Fenoll V., Mohamed-Balghata M. O., Gomez M. A., Alberto de Zarraga M., Rivas M. E., Gorgolas M., Svedhem-Johansson V., Flamholc L., Gisslen M., Hejdeman B., Norgren H., Wendahl S., Vourli, G, Noori, T, Pharris, A, Porter, K, Axelsson, M, Begovac, J, Cazein, F, Costagliola, D, Cowan, S, Croxford, S, Monforte, A, Delpech, V, Diaz, A, Girardi, E, Gunsenheimer-Bartmeyer, B, Hernando, V, Leierer, G, Lot, F, Nunez, O, Obel, N, Op de Coul, E, Paraskeva, D, Patrinos, S, Reiss, P, Schmid, D, Sonnerborg, A, Suligoi, B, Supervie, V, van Sighem, A, Zangerle, R, Touloumi, G, Egle, A, Kanatschnig, M, Ollinger, A, Rieger, A, Schmied, B, Wallner, E, Dewasurendra, D, Gisinger, M, Kitchen, M, Plattner, A, Rieser, E, Sarcletti, M, Greil, R, Schachner, M, Skocic, M, Muller, M, Aichwalder, R, Chromy, D, Grabmeier-Pfstershammer, K, Skoll, M, Touzeau, V, Cichon, P, Wolf-Nussmuller, S, Laferl, H, Zoufaly, A, Genger-Hackl, C, Kapper, A, Schneeberger, T, Trattner, E, Schober, G, Atzl, M, Hartmann, B, Puchhammer-Stockl, E, Berg, J, Appoyer, H, Rappold, M, Strickner, S, Schindelwig, K, Ledergerber, B, Fatkenheuer, G, Gerstof, J, Kronborg, G, Pedersen, C, Larsen, C, Pedersen, G, Mohey, R, Nielsen, L, Weise, L, Kvinesdal, B, Jensen, J, Abgrall, S, Bernard, L, Billaud, E, Boue, F, Boyer, L, Cabie, A, Caby, F, Canestri, A, Cotte, L, de Truchis, P, Duval, X, Duvivier, C, Enel, P, Fischer, H, Gasnault, J, Gaud, C, Grabar, S, Khuong-Josses, M, Launay, O, Marchand, L, Mary-Krause, M, Matheron, S, Melica-Gregoire, G, Melliez, H, Meynard, J, Nacher, M, Pavie, J, Piroth, L, Poizot-Martin, I, Pradier, C, Reynes, J, Rouveix, E, Simon, A, Slama, L, Tattevin, P, Tissot-Dupont, H, Biga, J, Kurth, T, Jacquemet, N, Guiguet, M, Leclercq, S, Lievre, L, Marshall, E, Roul, H, Selinger-Leneman, H, Potard, V, Benveniste, O, Breton, G, Lupin, C, Bourzam, E, Girard, P, Fonquernie, L, Valin, N, Lefebvre, B, Sebire, M, Pialoux, G, Lebrette, M, Tibaut, P, Adda, A, Hamidi, M, Cadranel, J, Lavole, A, Parrot, A, Bouchaud, O, Vignier, N, Mechai, F, Makhlouf, S, Honore, P, Bergmann, J, Delcey, V, Lopes, A, Sellier, P, Parrinello, M, Oksenhendler, E, Gerard, L, Molina, J, Rozenbaum, W, Denis, B, De Castro, N, Lascoux, C, Yazdanpanah, Y, Lariven, S, Joly, V, Rioux, C, Poupard, M, Taverne, B, Sutton, L, Masse, V, Genet, P, Wifaq, B, Gerbe, J, Grefe, S, Dupont, C, Freire Maresca, A, Reimann, E, Bloch, M, Meier, F, Mortier, E, Zeng, F, Montoya, B, Perronne, C, Mathez, D, Marigot-Outtandy, D, Berthe, H, Greder Belan, A, Terby, A, Godin Collet, C, Marque Juillet, S, Ruquet, M, Roussin-Bretagne, S, Colardelle, P, Granier, F, Laurichesse, J, Perronne, V, Akpan, T, Marcou, M, Daneluzzi, V, Veyssier-Belot, C, Masson, H, Welker, Y, Brazille, P, Kahn, J, Zucman, D, Majerholc, C, Fourn, E, Bornarel, D, Chambrin, V, Kansau, I, Raho-Moussa, M, Lelievre, J, Saidani, M, Chesnel, C, Dumont, C, Vittecoq, D, Derradji, O, Bolliot, C, Goujard, C, Teicher, E, Mole, M, Bourdic, K, Salmon, D, Le Jeunne, C, Guet, P, Pietri, M, Pannier Metzger, E, Marcou, V, Loulergue, P, Dupin, N, Morini, J, Deleuze, J, Gerhardt, P, Chanal, J, Weiss, L, Lucas, M, Jung, C, Ptak, M, Viard, J, Ghosn, J, Gazalet, P, Cros, A, Maignan, A, Lortholary, O, Rouzaud, C, Touam, F, Benhadj, K, Consigny, P, Bossi, P, Gergely, A, Cessot, G, Durand, F, Beck-Wirth, G, Michel, C, Benomar, M, Rey, D, Partisani, M, Cheneau, C, Batard, M, Fischer, P, Leclercq, P, Blanc, M, Morand, P, Epaulard, O, Signori-Schmuck, A, Laurichesse, H, Jacomet, C, Vidal, M, Coban, D, Casanova, S, Fresard, A, Guglielminotti, C, Botelho-Nevers, E, Brunon-Gagneux, A, Ronat, V, Verdon, R, Dargere, S, Haustraete, E, Feret, P, Goubin, P, Chavanet, P, Fillion, A, Croisier, D, Gohier, S, Arvieux, C, Souala, F, Chapplain, J, Ratajczak, M, Rohan, J, Faller, J, Ruyer, O, Gendrin, V, Toko, L, Chirouze, C, Hustache-Mathieu, L, Faucher, J, Proust, A, Magy-Bertrand, N, Gil, H, Meaux-Ruault, N, Sotto, A, Rouanet, I, Mauboussin, J, Doncesco, R, Jacques, G, May, T, Rabaud, C, Andre, M, Delestan, M, Bouillon, M, Bani-Sadr, F, Rouger, C, Berger, J, Nguyen, Y, Marchou, B, Delobel, P, Martin Blondel, G, Cuzin, L, Biezunski, N, Alric, L, Bonnet, D, Guivarch, M, Palacin, A, Payssan, V, Ajana, F, Meybeck, A, Viget, N, Pugliese, P, Roger, P, Rosenthal, E, Durant, J, Cua, E, Naqvi, A, Perbost, I, Risso, K, Quinsat, D, Raphael, S, Del Giudice, P, Dides, P, Sambuc, R, Antolini-Bouvenot, M, Druart, P, Meddeb, L, Ravaux, I, Menard, A, Tomei, C, Dhiver, C, Moreau, J, Mokhtari, S, Soavi, M, Tomas, V, Bregigeon, S, Faucher, O, Obry-Roguet, V, Ritleng, A, Petit, N, Bartoli, C, Ruiz, J, Blanc, D, Allegre, T, Sordage, M, Riou, J, Faudon, C, Slama, B, Zerazhi, H, Boulat, O, Chebrek, S, Beyrne, M, Granet Brunello, P, Pellissier, L, Bonnabel, D, Cohen Valensi, R, Mouchet, B, Mboungou, G, Lafeuillade, A, Hope-Rapp, E, Hittinger, G, Philip, G, Lambry, V, Raf, F, Allavena, C, Hall, N, Reliquet, V, Chidiac, C, Ferry, T, Perpoint, T, Miailhes, P, Boibieux, A, Livrozet, J, Makhlouf, D, Brunel, F, Chiarello, P, Hoen, B, Lamaury, I, Fabre, I, Samar, K, Duvallon, E, Clavel, C, Stegmann, S, Walter, V, Adriouch, L, Huber, F, Vanticlke, V, Couppie, P, Abel, S, Pierre-Francois, S, Ricaud, C, Rodet, R, Wartel, G, Sautron, C, Poubeau, P, Borgherini, G, Camuset, G, Arasteh, K, Kowohl Vivantes, S, Schurmann, D, Warncke Charite, M, Rockstroh, J, Wasmuth, J, Hass, S, Jensen, B, Feind, C, Esser, S, Schenk-Westkamp, P, Haberl, A, Stephan, C, Plettenberg, A, Kuhlendahl, F, Adam, A, Weitner, L, Schewe, K, Goey, H, Fenske, S, Buhk, T, Stellbrink, H, Hofmann, C, Hansen, S, Degen, O, Heuer, M, Stoll, M, Gerschmann, S, Horst, H, Trautmann, S, Gillor, D, Bogner, J, Sonntag, B, Salzberger, B, Fritzsche, C, Adamis, G, Antoniadou, A, Chini, M, Chrysos, G, Gikas, A, Gogos, H, Katsarou, O, Lazanas, M, Metallidis, S, Panagopoulos, P, Paparizos, V, Papastamopoulos, V, Paraskevis, D, Psychogiou, M, Sambatakou, H, Sipsas, N, Pantazis, N, Papadopoulos, A, Nitsotolis, T, Xylomenos, G, Marangos, M, Kouramba, A, Kontos, A, Lioni, A, Tsachouridou, O, Kourkounti, S, Ganitis, A, Barbounakis, E, d'Arminio Monforte, A, Antinori, A, Andreoni, M, Castagna, A, Castelli, F, Cauda, R, Di Perri, G, Galli, M, Iardino, R, Ippolito, G, Lazzarin, A, Marchetti, G, Rezza, G, von Schloesser, F, Viale, P, Ceccherini-Silberstein, F, Cozzi-Lepri, A, Lo Caputo, S, Mussini, C, Puoti, M, Perno, C, Bai, F, Balotta, C, Bandera, A, Bonora, S, Borderi, M, Calcagno, A, Capetti, A, Capobianchi, M, Cicalini, S, Cingolani, A, Cinque, P, Di Biagio, A, Gianotti, N, Gori, A, Guaraldi, G, Lapadula, G, Lichtner, M, Madeddu, G, Maggiolo, F, Monno, L, Nozza, S, Pinnetti, C, Quiros Roldan, E, Rossotti, R, Rusconi, S, Santoro, M, Saracino, A, Sarmati, L, Fanti, I, Galli, L, Lorenzini, P, Rodano, A, Macchia, M, Tavelli, A, Carletti, F, Carrara, S, Di Caro, A, Graziano, S, Petroni, F, Prota, G, Trufa, S, Giacometti, A, Costantini, A, Barocci, V, Angarano, G, Milano, E, Suardi, C, Donati, V, Verucchi, G, Castelnuovo, F, Minardi, C, Menzaghi, B, Abeli, C, Cacopardo, B, Celesia, B, Vecchiet, J, Falasca, K, Pan, A, Lorenzotti, S, Sighinolf, L, Segala, D, Blanc, P, Vichi, F, Cassola, G, Viscoli, C, Alessandrini, A, Bobbio, N, Mazzarello, G, Fondaco, L, Bonfanti, P, Molteni, C, Chiodera, A, Milini, P, Nunnari, G, Pellicano, G, Rizzardini, G, Cannizzo, E, Moioli, M, Piolini, R, Bernacchia, D, Salpietro, S, Tincati, C, Puzzolante, C, Migliorino, C, Sangiovanni, V, Borgia, G, Esposito, V, Di Flumeri, G, Gentile, I, Rizzo, V, Cattelan, A, Marinello, S, Cascio, A, Trizzino, M, Francisci, D, Schiaroli, E, Parruti, G, Sozio, F, Magnani, G, Ursitti, M, Cristaudo, A, Vullo, V, Acinapura, R, Moschese, D, Capozzi, M, Mondi, A, Rivano Capparuccia, M, Iaiani, G, Latini, A, Gagliardini, R, Plazzi, M, De Girolamo, G, Vergori, A, Cecchetto, M, Viviani, F, De Vito, A, Rossetti, B, Montagnani, F, Franco, A, Fontana Del Vecchio, R, Di Giuli, C, Caramello, P, Orofno, G, Sciandra, M, Bassetti, M, Londero, A, Manfrin, V, Battagin, G, Starnini, G, Ialungo, A, van der Valk, M, Geerlings, S, Goorhuis, A, Hovius, J, Lempkes, B, Nellen, F, van der Poll, T, Prins, J, van Vugt, M, Wiersinga, W, Wit, F, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A, Pijnappel, F, Smalhout, S, Weijsenfeld, A, Jurriaans, S, Back, N, Zaaijer, H, Berkhout, B, Cornelissen, M, Schinkel, C, Wolthers, K, Peters, E, van Agtmael, M, Bomers, M, Sigalof, K, Heitmuller, M, Laan, L, Ang, C, van Houdt, R, Jonges, M, van Prehn, J, Kuijpers, T, Pajkrt, D, Scherpbier, H, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Loof, L, Wintermans, B, Veenemans, J, Pronk, M, Ammerlaan, H, de Munnik, E, Jansz, A, Tjhie, J, Wegdam, M, Deiman, B, Scharnhorst, V, van Eeden, A, Brokking, W, Elsenburg, L, Nobel, H, Damen, M, van Kasteren, M, Berrevoets, M, Brouwer, A, Adams, A, de Kruijf-Van de Wiel, B, Keelan-Pfaf, S, van der Ven, B, Buiting, A, Murck, J, Versteeg, D, de Vries-Sluijs, T, Bax, H, van Gorp, E, Nouwen, J, Rijnders, B, Schurink, C, Verbon, A, de Jong-Peltenburg, N, Bassant, N, van Beek, J, Vriesde, M, van Zonneveld, L, van den Berg-Cameron, H, de Groot, J, Boucher, C, Koopmans, M, van Kampen, J, Fraaij, P, van Rossum, A, Vermont, C, van der Knaap, L, Visser, E, Branger, J, Douma, R, Duijf-Van de Ven, C, Schippers, E, van Nieuwkoop, C, van IJperen, J, Geilings, J, van der Hut, G, van Burgel, N, Leyten, E, Gelinck, L, Mollema, F, Davids-Veldhuis, S, Wildenbeest, G, Heikens, E, Groeneveld, P, Bouwhuis, J, Lammers, A, Kraan, S, van Hulzen, A, Kruiper, M, van der Bliek, G, Bor, P, Bloembergen, P, Wolfagen, M, Ruijs, G, Kroon, F, de Boer, M, Scheper, H, Jolink, H, Dorama, W, van Holten, N, Claas, E, Wessels, E, den Hollander, J, El Moussaoui, R, Pogany, K, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I, Havenith, T, Weijer, S, van Vonderen, M, Kampschreur, L, Faber, S, Steeman-Bouma, R, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F, Cohen Stuart, J, Jansen, E, Hoogewerf, M, Rozemeijer, W, van der Reijden, W, Sinnige, J, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Vrouenraets, S, Brouwer, C, Geerders, G, Hoeksema, K, Kleene, M, Knapen, M, van der Meche, I, Mulder-Seeleman, E, Toonen, A, Wijnands, S, Kwa, D, van Crevel, R, van Aerde, K, Doferhof, A, Henriet, S, ter Hofstede, H, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F, Burger, D, Gisolf, E, Hassing, R, Claassen, M, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, van der Prijt, L, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B, Veenendaal, D, Verhagen, D, Lauw, F, van Broekhuizen, M, van Wijk, M, Bierman, W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Scholvinck, E, Stienstra, Y, Verhage, A, Wouthuyzen-Bakker, K, Boonstra, A, de Groot-De Jonge, H, van der Meulen, P, de Weerd, D, Niesters, H, van Leer-Buter, C, Knoester, M, Hoepelman, A, Arends, J, Barth, R, Bruns, A, Ellerbroek, P, Mudrikova, T, Oosterheert, J, de Regt, M, Schadd, E, van Zoelen, M, Aarsman, K, Grifoen-Van Santen, B, de Kroon, I, van Rooijen, C, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Bont, L, Geelen, S, Loefen, Y, Wolfs, T, Nauta, N, Zaheri, S, Boyd, A, Bezemer, D, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Bretin, N, Djoechro, E, Geerlinks, J, Kruijne, E, Lodewijk, C, Lucas, E, van der Meer, R, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnorr, P, Tuijn, E, Veenenberg, L, Witte, E, Tuk, B, Moreno, S, del Amo, J, Dalmau, D, Navarro, M, Gonzalez, M, Blanco, J, Garcia, F, Rubio, R, Iribarren, J, Gutierrez, F, Vidal, F, Berenguer, J, Gonzalez, J, Sobrino, P, Alejos, B, Alvarez, D, Jarrin, I, Moreno, C, Munoz-Fernandez, M, Garcia-Merino, I, Rico, C, de la Fuente, J, Torre, A, Portilla, J, Merino, E, Reus, S, Boix, V, Giner, L, Gadea, C, Portilla, I, Pampliega, M, Diez, M, Rodriguez, J, Sanchez-Paya, J, Podzamczer, D, Imaz, E, Van Den Eyncle, E, Di Yacovo, S, Sumoy, M, Gomez, J, Hernandez, J, Aleman, M, Alonso, M, Hernandez, M, Diaz-Flores, F, Garcia, D, Pelazas, R, Asensi, V, Valle, E, Carton, J, Perez, V, Molina, M, Garcia, J, Carrera, E, Pulido, F, Bisbal, O, Matarranz, M, Lagarde, M, Rubio-Martin, R, Hernando, A, Bermejo, L, Dominguez, L, Arrizabalaga, J, Aramburu, M, Camino, X, Rodriguez-Arrondo, F, von Wichmann, M, Tome, L, Goenaga, M, Bustinduy, M, Galparsoro, H, Ibarguren, M, Aguado, M, Umerez, M, Masia, M, Lopez, C, Padilla, S, Navarro, A, Montolio, F, Robledano, C, Colome, J, Adsuar, A, Pascual, R, Carlos, F, Martinez, M, Fernandez, M, Garcia, E, Muga, R, Tor, J, Sanvisens, A, Bernaldo de Quiros Lopez, J, Miralles, P, Gutierrez, I, Ramirez, M, Padilla, B, Gijon, P, Carrero, A, Aldamiz-Echevarria, T, Tejerina, F, Parras, F, Balsalobre, P, Diez, C, Peraire, J, Vilades, C, Veloso, S, Vargas, M, Lopez-Dupla, M, Olona, M, Aguilar, A, Sirvent, J, Alba, V, Calavia, O, Montero, M, Lacruz, J, Blanes, M, Calabuig, E, Cuellar, S, Lopez, J, Salavert, M, de la Serna, I, Arribas, J, Montes, M, Pena, J, Arribas, B, Castro, J, Zamora, J, Perez, I, Estebanez, M, Garcia, S, Diaz, M, Alcariz, N, Mingorance, J, Montero, D, Gonzalez, A, Isabel de Jose, M, de los Santos, I, Sanz, J, Salas, A, Sarria, C, Berrocal, A, Garcia-Fraile, L, Oteo, J, Ibarra, V, Metola, L, Sanz, M, Perez-Martinez, L, Pascual, A, Ramos, C, Arazo, P, Gil, D, Jaen, A, Cairo, M, Irigoyen, D, Jordano, Q, Xercavins, M, Martinez-Lacasa, J, Velli, P, Font, R, Sanmarti, M, Ibanez, L, Rivero, M, Casado, M, Diaz, J, Uriz, J, Reparaz, J, Irigoyen, C, Arraiza, M, Segura, F, Amengual, M, Navarro, G, Sala, M, Cervantes, M, Pineda, V, Segura, V, Anton, E, Nogueras, M, Casado, J, Dronda, F, Moreno, A, Elias, M, Lopez, D, Gutierrez, C, Madrid, N, Lamas, A, Marti, P, de Diaz, A, Serrrano, S, Donat, L, Cano, A, Bernal, E, Munoz, A, Pena, A, Munoz, L, Parra, J, Alvarez, M, Chueca, N, Guillot, V, Vinuesa, D, Fernandez, J, Del Romero, J, Rodriguez, C, Puerta, T, Carrio, J, Vera, M, Ballesteros, J, Domingo, P, Sambeat, M, Lamarca, K, Mateo, G, Gutierrez, M, Fernandez, I, Antela, A, Losada, E, Riera, M, Penaranda, M, Leyes, M, Ribas, M, Campins, A, Vidal, C, Gil, L, Fanjul, F, Marinescu, C, Ribera, E, Santos, J, Marquez, M, Viciana, I, Palacios, R, Gonzalez, C, Viciana, P, Leal, M, Lopez-Cortes, L, Espinosa, N, Munoz, J, Zubero, M, Baraia-Etxaburu, J, Ibarra, S, Ferrero, O, Lopez de Munain, J, Camara, M, Lopez, I, de la Pena, M, Suarez-Garcia, I, Malmierca, E, Olalla, J, del Arco, A, de la Torre, J, Prada, J, Caracuel, Z, Lopez-Lirola, A, Lozano, A, Fernandez, E, Martinez, O, Vera, F, Martinez, L, Alcaraz, B, Jimeno, A, Poveda, E, Pernas, B, Mena, A, Grandal, M, Castro, A, Pedreira, J, Galera, C, Albendin, H, Iborra, A, Campillo, M, Vidal, A, Amador, C, Pasquau, F, Ena, J, Benito, C, Fenoll, V, Mohamed-Balghata, M, Gomez, M, Alberto de Zarraga, M, Rivas, M, Gorgolas, M, Svedhem-Johansson, V, Flamholc, L, Gisslen, M, Hejdeman, B, Norgren, H, Wendahl, S, Vourli G., Noori T., Pharris A., Porter K., Axelsson M., Begovac J., Cazein F., Costagliola D., Cowan S., Croxford S., Monforte A. D., Delpech V., Diaz A., Girardi E., Gunsenheimer-Bartmeyer B., Hernando V., Leierer G., Lot F., Nunez O., Obel N., Op de Coul E., Paraskeva D., Patrinos S., Reiss P., Schmid D., Sonnerborg A., Suligoi B., Supervie V., van Sighem A., Zangerle R., Touloumi G., Egle A., Kanatschnig M., Ollinger A., Rieger A., Schmied B., Wallner E., Dewasurendra D., Gisinger M., Kitchen M., Plattner A., Rieser E., Sarcletti M., Greil R., Schachner M., Skocic M., Muller M., Aichwalder R., Chromy D., Grabmeier-Pfstershammer K., Skoll M., Touzeau V., Cichon P., Wolf-Nussmuller S., Laferl H., Zoufaly A., Genger-Hackl C., Kapper A., Schneeberger T., Trattner E., Schober G., Atzl M., Hartmann B., Puchhammer-Stockl E., Berg J., Appoyer H., Rappold M., Strickner S., Schindelwig K., Ledergerber B., Fatkenheuer G., Gerstof J., Kronborg G., Pedersen C., Larsen C. 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- Abstract
Background. High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods. A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results. We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions. The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control.
- Published
- 2020
7. 2019 update of the European AIDS Clinical Society Guidelines for treatment of people living with HIV version 10.0
- Author
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Ryom, L, Cotter, A, De Miguel, R, Beguelin, C, Podlekareva, D, Arribas, J, Marzolini, C, Mallon, P, Rauch, A, Kirk, O, Molina, J, Guaraldi, G, Winston, A, Bhagani, S, Cinque, P, Kowalska, J, Collins, S, Battegay, M, De Miguel Buckley, R, D'Arminio Monforte, A, Bracchi, M, Dedes, N, Horban, A, Katlama, C, Latysheva, I, Lundgren, J, Mccormack, S, Mussini, C, Pozniak, A, Pulido, F, Raffi, F, Reiss, P, Stellbrink, H, Vasylyev, M, Gibbons, S, Livio, F, Behrens, G, Bower, M, Compston, J, De Wit, S, Fabbri, L, Fux, C, Gisslen, M, Martinez, E, Miro, J, Negredo, E, Poulter, N, Sebastiani, G, Berenguer, J, Boesecke, C, Bruno, R, Konov, S, Lacombe, K, Mauss, S, Mendao, L, Peters, L, Puoti, M, Rockstroh, J, Ambrosioni, J, De Castro, N, Fatkenheuer, G, Furrer, H, Oprea, C, Volny-Anne, A, Sullivan, A, Mulcahy, F, Wensing, A, Ryom L., Cotter A., De Miguel R., Beguelin C., Podlekareva D., Arribas J. R., Marzolini C., Mallon P. G. M., Rauch A., Kirk O., Molina J. M., Guaraldi G., Winston A., Bhagani S., Cinque P., Kowalska J. D., Collins S., Battegay M., De Miguel Buckley R., D'Arminio Monforte A., Bracchi M., Dedes N., Horban A., Katlama C., Latysheva I., Lundgren J. D., McCormack S., Mussini C., Pozniak A., Pulido F., Raffi F., Reiss P., Stellbrink H. -J., Vasylyev M., Gibbons S., Livio F., Behrens G., Bower M., Compston J., De Wit S., Fabbri L. M., Fux C. A., Gisslen M., Martinez E., Miro J. M., Negredo E., Poulter N., Sebastiani G., Berenguer J., Boesecke C., Bruno R., Konov S., Lacombe K., Mauss S., Mendao L., Peters L., Puoti M., Rockstroh J. K., Ambrosioni J., De Castro N., Fatkenheuer G., Furrer H., Oprea C., Volny-Anne A., Sullivan A., Mulcahy F., Wensing A., Ryom, L, Cotter, A, De Miguel, R, Beguelin, C, Podlekareva, D, Arribas, J, Marzolini, C, Mallon, P, Rauch, A, Kirk, O, Molina, J, Guaraldi, G, Winston, A, Bhagani, S, Cinque, P, Kowalska, J, Collins, S, Battegay, M, De Miguel Buckley, R, D'Arminio Monforte, A, Bracchi, M, Dedes, N, Horban, A, Katlama, C, Latysheva, I, Lundgren, J, Mccormack, S, Mussini, C, Pozniak, A, Pulido, F, Raffi, F, Reiss, P, Stellbrink, H, Vasylyev, M, Gibbons, S, Livio, F, Behrens, G, Bower, M, Compston, J, De Wit, S, Fabbri, L, Fux, C, Gisslen, M, Martinez, E, Miro, J, Negredo, E, Poulter, N, Sebastiani, G, Berenguer, J, Boesecke, C, Bruno, R, Konov, S, Lacombe, K, Mauss, S, Mendao, L, Peters, L, Puoti, M, Rockstroh, J, Ambrosioni, J, De Castro, N, Fatkenheuer, G, Furrer, H, Oprea, C, Volny-Anne, A, Sullivan, A, Mulcahy, F, Wensing, A, Ryom L., Cotter A., De Miguel R., Beguelin C., Podlekareva D., Arribas J. R., Marzolini C., Mallon P. G. M., Rauch A., Kirk O., Molina J. M., Guaraldi G., Winston A., Bhagani S., Cinque P., Kowalska J. D., Collins S., Battegay M., De Miguel Buckley R., D'Arminio Monforte A., Bracchi M., Dedes N., Horban A., Katlama C., Latysheva I., Lundgren J. D., McCormack S., Mussini C., Pozniak A., Pulido F., Raffi F., Reiss P., Stellbrink H. -J., Vasylyev M., Gibbons S., Livio F., Behrens G., Bower M., Compston J., De Wit S., Fabbri L. M., Fux C. A., Gisslen M., Martinez E., Miro J. M., Negredo E., Poulter N., Sebastiani G., Berenguer J., Boesecke C., Bruno R., Konov S., Lacombe K., Mauss S., Mendao L., Peters L., Puoti M., Rockstroh J. K., Ambrosioni J., De Castro N., Fatkenheuer G., Furrer H., Oprea C., Volny-Anne A., Sullivan A., Mulcahy F., and Wensing A.
- Abstract
Background: The European AIDS Clinical Society (EACS) Guidelines cover key aspects of HIV management with major updates every two years. Guideline highlights: The 2019 Guidelines were extended with a new section focusing on drug–drug interactions and other prescribing issues in people living with HIV (PLWH). The recommendations for treatment-naïve PLWH were updated with four preferred regimens favouring unboosted integrase inhibitors. A two-drug regimen with dolutegravir and lamivudine, and a three-drug regimen including doravirine were also added to the recommended initial regimens. Lower thresholds for hypertension were expanded to all PLWH and for cardiovascular disease prevention, the 10-year predicted risk threshold for consideration of antiretroviral therapy (ART) modification was lowered from 20% to 10%. Frailty and obesity were added as new topics. It was specified to use urine albumin to creatinine ratio to screen for glomerular disease and urine protein to creatinine ratio for tubular diseases, and thresholds were streamlined with the Kidney Disease: Improving Global Outcomes (KDIGO) recommendations. Hepatitis C virus (HCV) treatment recommendations were split into preferred and alternative treatment options. The algorithm for management of recently acquired HCV infection was updated and includes recommendations for early chronic infection management. Treatment of resistant tuberculosis (TB) was streamlined with the World Health Organization (WHO) recommendations, and new tables on immune reconstitution inflammatory syndrome, on when to start ART in the presence of opportunistic infections and on TB drug dosing were included. Conclusions: The EACS Guidelines underwent major revisions of all sections in 2019. They are available in four different formats including a new interactive web-based version and are translated into Chinese, French, German, Japanese, Portuguese, Russian and Spanish.
- Published
- 2020
8. Human Immunodeficiency Virus Continuum of Care in 11 European Union Countries at the End of 2016 Overall and by Key Population: Have We Made Progress?
- Author
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Vourli, G., Noori, T., Pharris, A., Porter, K., Axelsson, M., Begovac, J., Cazein, F., Costagliola, D., Cowan, S., Croxford, S., Monforte, A. D., Delpech, V., Diaz, A., Girardi, E., Gunsenheimer-Bartmeyer, B., Hernando, V., Leierer, G., Lot, F., Nunez, O., Obel, N., Op de Coul, E., Paraskeva, D., Patrinos, S., Reiss, P., Schmid, D., Sonnerborg, A., Suligoi, B., Supervie, V., van Sighem, A., Zangerle, R., Touloumi, G., Egle, A., Kanatschnig, M., Ollinger, A., Rieger, A., Schmied, B., Wallner, E., Dewasurendra, D., Gisinger, M., Kitchen, M., Plattner, A., Rieser, E., Sarcletti, M., Greil, R., Schachner, M., Skocic, M., Muller, M., Aichwalder, R., Chromy, D., Grabmeier-Pfstershammer, K., Skoll, M., Touzeau, V., Cichon, P., Wolf-Nussmuller, S., Laferl, H., Zoufaly, A., Genger-Hackl, C., Kapper, A., Schneeberger, T., Trattner, E., Schober, G., Atzl, M., Hartmann, B., Puchhammer-Stockl, E., Berg, J., Appoyer, H., Rappold, M., Strickner, S., Schindelwig, K., Ledergerber, B., Fatkenheuer, G., Gerstof, J., Kronborg, G., Pedersen, C., Larsen, C. S., Pedersen, G., Mohey, R., Nielsen, L., Weise, L., Kvinesdal, B., Jensen, J., Abgrall, S., Bernard, L., Billaud, E., Boue, F., Boyer, L., Cabie, A., Caby, F., Canestri, A., Cotte, L., de Truchis, P., Duval, X., Duvivier, C., Enel, P., Fischer, H., Gasnault, J., Gaud, C., Grabar, S., Khuong-Josses, M. A., Launay, O., Marchand, L., Mary-Krause, M., Matheron, S., Melica-Gregoire, G., Melliez, H., Meynard, J. L., Nacher, M., Pavie, J., Piroth, L., Poizot-Martin, I., Pradier, C., Reynes, J., Rouveix, E., Simon, A., Slama, L., Tattevin, P., Tissot-Dupont, H., Biga, J., Kurth, T., Jacquemet, N., Guiguet, M., Leclercq, S., Lievre, L., Marshall, E., Roul, H., Selinger-Leneman, H., Potard, V., Benveniste, O., Breton, G., Lupin, C., Bourzam, E., Girard, P. M., Fonquernie, L., Valin, N., Lefebvre, B., Sebire, M., Pialoux, G., Lebrette, M. G., Tibaut, P., Adda, A., Hamidi, M., Cadranel, J., Lavole, A., Parrot, A., Bouchaud, O., Vignier, N., Mechai, F., Makhlouf, S., Honore, P., Bergmann, J. F., Delcey, V., Lopes, A., Sellier, P., Parrinello, M., Oksenhendler, E., Gerard, L., Molina, J. M., Rozenbaum, W., Denis, B., De Castro, N., Lascoux, C., Yazdanpanah, Y., Lariven, S., Joly, V., Rioux, C., Poupard, M., Taverne, B., Sutton, L., Masse, V., Genet, P., Wifaq, B., Gerbe, J., Grefe, S., Dupont, C., Freire Maresca, A., Reimann, E., Bloch, M., Meier, F., Mortier, E., Zeng, F., Montoya, B., Perronne, C., Mathez, D., Marigot-Outtandy, D., Berthe, H., Greder Belan, A., Terby, A., Godin Collet, C., Marque Juillet, S., Ruquet, M., Roussin-Bretagne, S., Colardelle, P., Granier, F., Laurichesse, J. J., Perronne, V., Akpan, T., Marcou, M., Daneluzzi, V., Veyssier-Belot, C., Masson, H., Welker, Y., Brazille, P., Kahn, J. E., Zucman, D., Majerholc, C., Fourn, E., Bornarel, D., Chambrin, V., Kansau, I., Raho-Moussa, M., Lelievre, J. D., Saidani, M., Chesnel, C., Dumont, C., Vittecoq, D., Derradji, O., Bolliot, C., Goujard, C., Teicher, E., Mole, M., Bourdic, K., Salmon, D., Le Jeunne, C., Guet, P., Pietri, M. P., Pannier Metzger, E., Marcou, V., Loulergue, P., Dupin, N., Morini, J. P., Deleuze, J., Gerhardt, P., Chanal, J., Weiss, L., Lucas, M. L., Jung, C., Ptak, M., Viard, J. P., Ghosn, J., Gazalet, P., Cros, A., Maignan, A., Lortholary, O., Rouzaud, C., Touam, F., Benhadj, K., Consigny, P. H., Bossi, P., Gergely, A., Cessot, G., Durand, F., Beck-Wirth, G., Michel, C., Benomar, M., Rey, D., Partisani, M., Cheneau, C., Batard, M. L., Fischer, P., Leclercq, P., Blanc, M., Morand, P., Epaulard, O., Signori-Schmuck, A., Laurichesse, H., Jacomet, C., Vidal, M., Coban, D., Casanova, S., Fresard, A., Guglielminotti, C., Botelho-Nevers, E., Brunon-Gagneux, A., Ronat, V., Verdon, R., Dargere, S., Haustraete, E., Feret, P., Goubin, P., Chavanet, P., Fillion, A., Croisier, D., Gohier, S., Arvieux, C., Souala, F., Chapplain, J. M., Ratajczak, M., Rohan, J., Faller, J. P., Ruyer, O., Gendrin, V., Toko, L., Chirouze, C., Hustache-Mathieu, L., Faucher, J. F., Proust, A., Magy-Bertrand, N., Gil, H., Meaux-Ruault, N., Sotto, A., Rouanet, I., Mauboussin, J. M., Doncesco, R., Jacques, G., May, T., Rabaud, C., Andre, M., Delestan, M., Bouillon, M. P., Bani-Sadr, F., Rouger, C., Berger, J. L., Nguyen, Y., Marchou, B., Delobel, P., Martin Blondel, G., Cuzin, L., Biezunski, N., Alric, L., Bonnet, D., Guivarch, M., Palacin, A., Payssan, V., Ajana, F., Meybeck, A., Viget, N., Pugliese, P., Roger, P. M., Rosenthal, E., Durant, J., Cua, E., Naqvi, A., Perbost, I., Risso, K., Quinsat, D., Raphael, St., Del Giudice, P., Dides, P. Y., Sambuc, R., Antolini-Bouvenot, M. S., Druart, P., Meddeb, L., Ravaux, I., Menard, A., Tomei, C., Dhiver, C., Moreau, J., Mokhtari, S., Soavi, M. J., Tomas, V., Bregigeon, S., Faucher, O., Obry-Roguet, V., Ritleng, A. S., Petit, N., Bartoli, C., Ruiz, J. M., Blanc, D., Allegre, T., Sordage, M., Riou, J. M., Faudon, C., Slama, B., Zerazhi, H., Boulat, O., Chebrek, S., Beyrne, M., Granet Brunello, P., Pellissier, L., Bonnabel, D., Cohen Valensi, R., Mouchet, B., Mboungou, G., Lafeuillade, A., Hope-Rapp, E., Hittinger, G., Philip, G., Lambry, V., Raf, F., Allavena, C., Hall, N., Reliquet, V., Chidiac, C., Ferry, T., Perpoint, T., Miailhes, P., Boibieux, A., Livrozet, J. M., Makhlouf, D., Brunel, F., Chiarello, P., Hoen, B., Lamaury, I., Fabre, I., Samar, K., Duvallon, E., Clavel, C., Stegmann, S., Walter, V., Adriouch, L., Huber, F., Vanticlke, V., Couppie, P., Abel, S., Pierre-Francois, S., Ricaud, C., Rodet, R., Wartel, G., Sautron, C., Poubeau, P., Borgherini, G., Camuset, G., Arasteh, K., Kowohl Vivantes, S., Schurmann, D., Warncke Charite, M., Rockstroh, J., Wasmuth, J., Hass, S., Jensen, B. O., Feind, C., Esser, S., Schenk-Westkamp, P., Haberl, A., Stephan, C., Plettenberg, A., Kuhlendahl, F., Adam, A., Weitner, L., Schewe, K., Goey, H., Fenske, S., Buhk, T., Stellbrink, H. J., Hofmann, C., Hansen, S., Degen, O., Heuer, M., Stoll, M., Gerschmann, S., Horst, H., Trautmann, S., Gillor, D., Bogner, J., Sonntag, B., Salzberger, B., Fritzsche, C., Adamis, G., Antoniadou, A., Chini, M., Chrysos, G., Gikas, A., Gogos, H. A., Katsarou, O., Lazanas, M., Metallidis, S., Panagopoulos, P., Paparizos, V., Papastamopoulos, V., Paraskevis, D., Psychogiou, M., Sambatakou, H., Sipsas, N. V., Pantazis, N., Papadopoulos, A., Nitsotolis, T., Xylomenos, G., Marangos, M. N., Kouramba, A., Kontos, A., Lioni, A., Tsachouridou, O., Kourkounti, S., Ganitis, A., Barbounakis, E., d'Arminio Monforte, A., Antinori, A., Andreoni, M., Castagna, A., Castelli, F., Cauda, R., Di Perri, G., Galli, M., Iardino, R., Ippolito, G., Lazzarin, A., Marchetti, G. C., Rezza, G., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Cozzi-Lepri, A., Lo Caputo, S., Mussini, C., Puoti, M., Perno, C. F., Bai, F., Balotta, C., Bandera, A., Bonora, S., Borderi, M., Calcagno, A., Capetti, A., Capobianchi, M. R., Cicalini, S., Cingolani, A., Cinque, P., Di Biagio, A., Gianotti, N., Gori, A., Guaraldi, G., Lapadula, G., Lichtner, M., Madeddu, G., Maggiolo, F., Marchetti, G., Monno, L., Nozza, S., Pinnetti, C., Quiros Roldan, E., Rossotti, R., Rusconi, S., Santoro, M. M., Saracino, A., Sarmati, L., Fanti, I., Galli, L., Lorenzini, P., Rodano, A., Macchia, M., Tavelli, A., Carletti, F., Carrara, S., Di Caro, A., Graziano, S., Petroni, F., Prota, G., Trufa, S., Giacometti, A., Costantini, A., Barocci, V., Angarano, G., Milano, E., Suardi, C., Donati, V., Verucchi, G., Castelnuovo, F., Minardi, C., Menzaghi, B., Abeli, C., Cacopardo, B., Celesia, B., Vecchiet, J., Falasca, K., Pan, A., Lorenzotti, S., Sighinolf, L., Segala, D., Blanc, P., Vichi, F., Cassola, G., Viscoli, C., Alessandrini, A., Bobbio, N., Mazzarello, G., Fondaco, L., Bonfanti, P., Molteni, C., Chiodera, A., Milini, P., Nunnari, G., Pellicano, G., Rizzardini, G., Cannizzo, E. S., Moioli, M. C., Piolini, R., Bernacchia, D., Salpietro, S., Tincati, C., Puzzolante, C., Migliorino, C., Sangiovanni, V., Borgia, G., Esposito, V., Di Flumeri, G., Gentile, I., Rizzo, V., Cattelan, A. M., Marinello, S., Cascio, A., Trizzino, M., Francisci, D., Schiaroli, E., Parruti, G., Sozio, F., Magnani, G., Ursitti, M. A., Cristaudo, A., Vullo, V., Acinapura, R., Moschese, D., Capozzi, M., Mondi, A., Rivano Capparuccia, M., Iaiani, G., Latini, A., Gagliardini, R., Plazzi, M. M., De Girolamo, G., Vergori, A., Cecchetto, M., Viviani, F., De Vito, A., Rossetti, B., Montagnani, F., Franco, A., Fontana Del Vecchio, R., Di Giuli, C., Caramello, P., Orofno, G. C., Sciandra, M., Bassetti, M., Londero, A., Manfrin, V., Battagin, G., Starnini, G., Ialungo, A., van der Valk, M., Geerlings, S. E., Goorhuis, A., Hovius, J. W., Lempkes, B., Nellen, F. J. B., van der Poll, T., Prins, J. M., van Vugt, M., Wiersinga, W. J., Wit, F. W. M. N., van Duinen, M., van Eden, J., Hazenberg, A., van Hes, A. M. H., Pijnappel, F. J. J., Smalhout, S. Y., Weijsenfeld, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Peters, E. J. G., van Agtmael, M. A., Bomers, M., Sigalof, K. C. E., Heitmuller, M., Laan, L. M., Ang, C. W., van Houdt, R., Jonges, M., van Prehn, J., Kuijpers, T. W., Pajkrt, D., Scherpbier, H. J., de Boer, C., van der Plas, A., van den Berge, M., Stegeman, A., Baas, S., Hage de Loof, L., Wintermans, B., Veenemans, J., Pronk, M. J. H., Ammerlaan, H. S. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van Eeden, A., Brokking, W., Elsenburg, L. J. M., Nobel, H., Damen, M., van Kasteren, M. E. E., Berrevoets, M. A. H., Brouwer, A. E., Adams, A., de Kruijf-Van de Wiel, B. A. F. M., Keelan-Pfaf, S., van der Ven, B., Buiting, A. G. M., Murck, J. L., Versteeg, D., de Vries-Sluijs, T. E. M. S., Bax, H. I., van Gorp, E. C. M., Nouwen, J. L., Rijnders, B. J. A., Schurink, C. A. M., Verbon, A., de Jong-Peltenburg, N. C., Bassant, N., van Beek, J. E. A., Vriesde, M., van Zonneveld, L. M., van den Berg-Cameron, H. J., de Groot, J., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E., Branger, J., Douma, R. A., Duijf-Van de Ven, C. J. H. M., Schippers, E. F., van Nieuwkoop, C., van IJperen, J. M., Geilings, J., van der Hut, G., van Burgel, N. D., Leyten, E. M. S., Gelinck, L. B. S., Mollema, F., Davids-Veldhuis, S., Wildenbeest, G. S., Heikens, E., Groeneveld, P. H. P., Bouwhuis, J. W., Lammers, A. J. J., Kraan, S., van Hulzen, A. G. W., Kruiper, M. S. M., van der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfagen, M. J. H. M., Ruijs, G. J. H. M., Kroon, F. P., de Boer, M. G. J., Scheper, H., Jolink, H., Dorama, W., van Holten, N., Claas, E. C. J., Wessels, E., den Hollander, J. G., El Moussaoui, R., Pogany, K., Kastelijns, M., Smit, J. V., Smit, E., Struik-Kalkman, D., Tearno, C., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A. M. L., Posthouwer, D., Ackens, R. P., Burgers, K., Schippers, J., Weijenberg-Maes, B., van Loo, I. H. M., Havenith, T. R. A., Weijer, S., van Vonderen, M. G. A., Kampschreur, L. M., Faber, S., Steeman-Bouma, R., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-Van de Plas, M., Heins, H., Kortmann, W., van Twillert, G., Renckens, R., Ruiter-Pronk, D., van Truijen-Oud, F. A., Cohen Stuart, J. W. T., Jansen, E. R., Hoogewerf, M., Rozemeijer, W., van der Reijden, W. A., Sinnige, J. C., Brinkman, K., van den Berk, G. E. L., Blok, W. L., Frissen, P. H. J., Lettinga, K. D., Schouten, W. E. M., Veenstra, J., Vrouenraets, S. M. E., Brouwer, C. J., Geerders, G. F., Hoeksema, K., Kleene, M. J., Knapen, M., van der Meche, I. B., Mulder-Seeleman, E., Toonen, A. J. M., Wijnands, S., Kwa, D., van Crevel, R., van Aerde, K., Doferhof, A. S. M., Henriet, S. S. V., ter Hofstede, H. J. M., Hoogerwerf, J., Keuter, M., Richel, O., Albers, M., Grintjes-Huisman, K. J. T., de Haan, M., Marneef, M., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Burger, D., Gisolf, E. H., Hassing, R. J., Claassen, M., ter Beest, G., van Bentum, P. H. M., Langebeek, N., Tiemessen, R., Swanink, C. M. A., van Lelyveld, S. F. L., Soetekouw, R., van der Prijt, L. M. M., van der Swaluw, J., Bermon, N., Jansen, R., Herpers, B. L., Veenendaal, D., Verhagen, D. W. M., Lauw, F. N., van Broekhuizen, M. C., van Wijk, M., Bierman, W. F. W., Bakker, M., Kleinnijenhuis, J., Kloeze, E., Middel, A., Scholvinck, E. H., Stienstra, Y., Verhage, A. R., Wouthuyzen-Bakker, K. M., Boonstra, A., de Groot-De Jonge, H., van der Meulen, P. A., de Weerd, D. A., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Hoepelman, A. I. M., Arends, J. E., Barth, R. E., Bruns, A. H. W., Ellerbroek, P. M., Mudrikova, T., Oosterheert, J. J., de Regt, M. J. A., Schadd, E. M., van Zoelen, M. A. D., Aarsman, K., Grifoen-Van Santen, B. M. G., de Kroon, I., van Rooijen, C. S. A. M., van Berkel, M., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Bont, L. J., Geelen, S. P. M., Loefen, Y. G. T., Wolfs, T. F. W., Nauta, N., Zaheri, S., Boyd, A. C., Bezemer, D. O., van Sighem, A. I., Smit, C., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Meijering, R., van de Sande, L., Rutkens, T., van der Vliet, S., de Groot, L., van den Akker, M., Bakker, Y., El Berkaoui, A., Bezemer, M., Bretin, N., Djoechro, E., Geerlinks, J., Kruijne, E., Lodewijk, C., Lucas, E., van der Meer, R., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., Witte, E. C., Tuk, B., Moreno, S., del Amo, J., Dalmau, D., Navarro, M. L., Gonzalez, M. I., Blanco, J. L., Garcia, F., Rubio, R., Iribarren, J. 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K., Doferhof A.S.M., Henriet S.S.V., ter Hofstede H.J.M., Hoogerwerf J., Keuter M., Richel O., Albers M., Grintjes-Huisman K.J.T., de Haan M., Marneef M., Strik-Albers R., Rahamat-Langendoen J., Stelma F.F., Burger D., Gisolf E.H., Hassing R.J., Claassen M., ter Beest G., van Bentum P.H.M., Langebeek N., Tiemessen R., Swanink C.M.A., van Lelyveld S.F.L., Soetekouw R., van der Prijt L.M.M., van der Swaluw J., Bermon N., Jansen R., Herpers B.L., Veenendaal D., Verhagen D.W.M., Lauw F.N., van Broekhuizen M.C., van Wijk M., Bierman W.F.W., Bakker M., Kleinnijenhuis J., Kloeze E., Middel A., Scholvinck E.H., Stienstra Y., Verhage A.R., Wouthuyzen-Bakker K.M., Boonstra A., de Groot-De Jonge H., van der Meulen P.A., de Weerd D.A., Niesters H.G.M., van Leer-Buter C.C., Knoester M., Hoepelman A.I.M., Arends J.E., Barth R.E., Bruns A.H.W., Ellerbroek P.M., Mudrikova T., Oosterheert J.J., de Regt M.J.A., Schadd E.M., van Zoelen M.A.D., Aarsman K., Grifoen-Van Santen B.M.G., de Kroon I., van Rooijen C.S.A.M., van Berkel M., Schuurman R., Verduyn-Lunel F., Wensing A.M.J., Bont L.J., Geelen S.P.M., Loefen Y.G.T., Wolfs T.F.W., Nauta N., Zaheri S., Boyd A.C., Bezemer D.O., van Sighem A.I., Smit C., Hillebregt M., de Jong A., Woudstra T., Bergsma D., Meijering R., van de Sande L., Rutkens T., van der Vliet S., de Groot L., van den Akker M., Bakker Y., El Berkaoui A., Bezemer M., Bretin N., Djoechro E., Geerlinks J., Kruijne E., Lodewijk C., Lucas E., van der Meer R., Munjishvili L., Paling F., Peeck B., Ree C., Regtop R., Ruijs Y., Schoorl M., Schnorr P., Tuijn E., Veenenberg L., Witte E.C., Tuk B., Moreno S., del Amo J., Dalmau D., Navarro M.L., Gonzalez M.I., Blanco J.L., Garcia F., Rubio R., Iribarren J.A., Gutierrez F., Vidal F., Berenguer J., Gonzalez J., Sobrino P., Alejos B., Alvarez D., Jarrin I., Moreno C., Munoz-Fernandez M.A., Garcia-Merino I., Rico C.G., de la Fuente J.G., Torre A.G., Portilla J., Merino E., Reus S., Boix V., Giner L., Gadea C., Portilla I., 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Pedreira J.D., Galera C., Albendin H., Iborra A., Campillo M.A., Vidal A., Amador C., Pasquau F., Ena J., Benito C., Fenoll V., Mohamed-Balghata M.O., Gomez M.A., Alberto de Zarraga M., Rivas M.E., Gorgolas M., Svedhem-Johansson V., Flamholc L., Gisslen M., Hejdeman B., Norgren H., Wendahl S., Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, ANS - Neuroinfection & -inflammation, Internal medicine, Medical Microbiology and Infection Prevention, AMS - Rehabilitation & Development, VU University medical center, Amsterdam Gastroenterology Endocrinology Metabolism, Pediatric surgery, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pulmonary medicine, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Ethics, Law & Medical humanities, APH - Quality of Care, ACS - Pulmonary hypertension & thrombosis, Amsterdam Neuroscience - Neuroinfection & -inflammation, Amsterdam Reproduction & Development (AR&D), APH - Societal Participation & Health, Pediatrics, HAL-SU, Gestionnaire, National and Kapodistrian University of Athens (NKUA), University College of London [London] (UCL), Public Health Agency of Sweden, University of Zagreb, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Statens Serum Institut [Copenhagen], Public Health England [London], Università degli Studi di Milano = University of Milan (UNIMI), Instituto de Salud Carlos III [Madrid] (ISC), Istituto Nazionale di Malattie Infettive 'Lazzaro Spallanzani' (INMI), Robert Koch Institute [Berlin] (RKI), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), University of Copenhagen = Københavns Universitet (UCPH), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Hellenic Center for Disease Control and Prevention, Amsterdam UMC - Amsterdam University Medical Center, Austrian Agency for Health and Food Safety (AGES), Department of Infectious Diseases, Institution of Medicine, Karolinska University Hospital and Karolinska Institutet, Istituto Superiore di Sanita [Rome], Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), University of Athens Medical School [Athens], Vourli, G, Noori, T, Pharris, A, Porter, K, Axelsson, M, Begovac, J, Cazein, F, Costagliola, D, Cowan, S, Croxford, S, Monforte, A, Delpech, V, Diaz, A, Girardi, E, Gunsenheimer-Bartmeyer, B, Hernando, V, Leierer, G, Lot, F, Nunez, O, Obel, N, Op de Coul, E, Paraskeva, D, Patrinos, S, Reiss, P, Schmid, D, Sonnerborg, A, Suligoi, B, Supervie, V, van Sighem, A, Zangerle, R, Touloumi, G, Egle, A, Kanatschnig, M, Ollinger, A, Rieger, A, Schmied, B, Wallner, E, Dewasurendra, D, Gisinger, M, Kitchen, M, Plattner, A, Rieser, E, Sarcletti, 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Hollander, J, El Moussaoui, R, Pogany, K, Kastelijns, M, Smit, J, Smit, E, Struik-Kalkman, D, Tearno, C, van Niekerk, T, Pontesilli, O, Lowe, S, Oude Lashof, A, Posthouwer, D, Ackens, R, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I, Havenith, T, Weijer, S, van Vonderen, M, Kampschreur, L, Faber, S, Steeman-Bouma, R, Weel, J, Kootstra, G, Delsing, C, van der Burg-Van de Plas, M, Heins, H, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F, Cohen Stuart, J, Jansen, E, Hoogewerf, M, Rozemeijer, W, van der Reijden, W, Sinnige, J, Brinkman, K, van den Berk, G, Blok, W, Frissen, P, Lettinga, K, Schouten, W, Veenstra, J, Vrouenraets, S, Brouwer, C, Geerders, G, Hoeksema, K, Kleene, M, Knapen, M, van der Meche, I, Mulder-Seeleman, E, Toonen, A, Wijnands, S, Kwa, D, van Crevel, R, van Aerde, K, Doferhof, A, Henriet, S, ter Hofstede, H, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F, Burger, D, Gisolf, E, Hassing, R, Claassen, M, ter Beest, G, van Bentum, P, Langebeek, N, Tiemessen, R, Swanink, C, van Lelyveld, S, Soetekouw, R, van der Prijt, L, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B, Veenendaal, D, Verhagen, D, Lauw, F, van Broekhuizen, M, van Wijk, M, Bierman, W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Scholvinck, E, Stienstra, Y, Verhage, A, Wouthuyzen-Bakker, K, Boonstra, A, de Groot-De Jonge, H, van der Meulen, P, de Weerd, D, Niesters, H, van Leer-Buter, C, Knoester, M, Hoepelman, A, Arends, J, Barth, R, Bruns, A, Ellerbroek, P, Mudrikova, T, Oosterheert, J, de Regt, M, Schadd, E, van Zoelen, M, Aarsman, K, Grifoen-Van Santen, B, de Kroon, I, van Rooijen, C, van Berkel, M, Schuurman, R, Verduyn-Lunel, F, Wensing, A, Bont, L, Geelen, S, Loefen, Y, Wolfs, T, Nauta, N, Zaheri, S, Boyd, A, Bezemer, D, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Bretin, N, Djoechro, E, Geerlinks, J, Kruijne, E, Lodewijk, C, Lucas, E, van der Meer, R, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnorr, P, Tuijn, E, Veenenberg, L, Witte, E, Tuk, B, Moreno, S, del Amo, J, Dalmau, D, Navarro, M, Gonzalez, M, Blanco, J, Garcia, F, Rubio, R, Iribarren, J, Gutierrez, F, Vidal, F, Berenguer, J, Gonzalez, J, Sobrino, P, Alejos, B, Alvarez, D, Jarrin, I, Moreno, C, Munoz-Fernandez, M, Garcia-Merino, I, Rico, C, de la Fuente, J, Torre, A, Portilla, J, Merino, E, Reus, S, Boix, V, Giner, L, Gadea, C, Portilla, I, Pampliega, M, Diez, M, Rodriguez, J, Sanchez-Paya, J, Podzamczer, D, Imaz, E, Van Den Eyncle, E, Di Yacovo, S, Sumoy, M, Gomez, J, Hernandez, J, Aleman, M, Alonso, M, Hernandez, M, Diaz-Flores, F, Garcia, D, Pelazas, R, Asensi, V, Valle, E, Carton, J, Perez, V, Molina, M, Garcia, J, Carrera, E, Pulido, F, Bisbal, O, Matarranz, M, Lagarde, M, Rubio-Martin, R, Hernando, A, Bermejo, L, Dominguez, L, Arrizabalaga, J, Aramburu, M, Camino, X, Rodriguez-Arrondo, F, von Wichmann, M, Tome, L, Goenaga, M, Bustinduy, M, Galparsoro, H, Ibarguren, M, Aguado, M, Umerez, M, Masia, M, Lopez, C, Padilla, S, Navarro, A, Montolio, F, Robledano, C, Colome, J, Adsuar, A, Pascual, R, Carlos, F, Martinez, M, Fernandez, M, Garcia, E, Muga, R, Tor, J, Sanvisens, A, Bernaldo de Quiros Lopez, J, Miralles, P, Gutierrez, I, Ramirez, M, Padilla, B, Gijon, P, Carrero, A, Aldamiz-Echevarria, T, Tejerina, F, Parras, F, Balsalobre, P, Diez, C, Peraire, J, Vilades, C, Veloso, S, Vargas, M, Lopez-Dupla, M, Olona, M, Aguilar, A, Sirvent, J, Alba, V, Calavia, O, Montero, M, Lacruz, J, Blanes, M, Calabuig, E, Cuellar, S, Lopez, J, Salavert, M, de la Serna, I, Arribas, J, Montes, M, Pena, J, Arribas, B, Castro, J, Zamora, J, Perez, I, Estebanez, M, Garcia, S, Diaz, M, Alcariz, N, Mingorance, J, Montero, D, Gonzalez, A, Isabel de Jose, M, de los Santos, I, Sanz, J, Salas, A, Sarria, C, Berrocal, A, Garcia-Fraile, L, Oteo, J, Ibarra, V, Metola, L, Sanz, M, Perez-Martinez, L, Pascual, A, Ramos, C, Arazo, P, Gil, D, Jaen, A, Cairo, M, Irigoyen, D, Jordano, Q, Xercavins, M, Martinez-Lacasa, J, Velli, P, Font, R, Sanmarti, M, Ibanez, L, Rivero, M, Casado, M, Diaz, J, Uriz, J, Reparaz, J, Irigoyen, C, Arraiza, M, Segura, F, Amengual, M, Navarro, G, Sala, M, Cervantes, M, Pineda, V, Segura, V, Anton, E, Nogueras, M, Casado, J, Dronda, F, Moreno, A, Elias, M, Lopez, D, Gutierrez, C, Madrid, N, Lamas, A, Marti, P, de Diaz, A, Serrrano, S, Donat, L, Cano, A, Bernal, E, Munoz, A, Pena, A, Munoz, L, Parra, J, Alvarez, M, Chueca, N, Guillot, V, Vinuesa, D, Fernandez, J, Del Romero, J, Rodriguez, C, Puerta, T, Carrio, J, Vera, M, Ballesteros, J, Domingo, P, Sambeat, M, Lamarca, K, Mateo, G, Gutierrez, M, Fernandez, I, Antela, A, Losada, E, Riera, M, Penaranda, M, Leyes, M, Ribas, M, Campins, A, Vidal, C, Gil, L, Fanjul, F, Marinescu, C, Ribera, E, Santos, J, Marquez, M, Viciana, I, Palacios, R, Gonzalez, C, Viciana, P, Leal, M, Lopez-Cortes, L, Espinosa, N, Munoz, J, Zubero, M, Baraia-Etxaburu, J, Ibarra, S, Ferrero, O, Lopez de Munain, J, Camara, M, Lopez, I, de la Pena, M, Suarez-Garcia, I, Malmierca, E, Olalla, J, del Arco, A, de la Torre, J, Prada, J, Caracuel, Z, Lopez-Lirola, A, Lozano, A, Fernandez, E, Martinez, O, Vera, F, Martinez, L, Alcaraz, B, Jimeno, A, Poveda, E, Pernas, B, Mena, A, Grandal, M, Castro, A, Pedreira, J, Galera, C, Albendin, H, Iborra, A, Campillo, M, Vidal, A, Amador, C, Pasquau, F, Ena, J, Benito, C, Fenoll, V, Mohamed-Balghata, M, Gomez, M, Alberto de Zarraga, M, Rivas, M, Gorgolas, M, Svedhem-Johansson, V, Flamholc, L, Gisslen, M, Hejdeman, B, Norgren, H, and Wendahl, S
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Male ,0301 basic medicine ,Psychological intervention ,Human immunodeficiency virus (HIV) ,Medizin ,Continuum of care ,Europe ,HIV infection ,Key population ,Sex ,Anti-Retroviral Agents ,Continuity of Patient Care ,European Union ,HIV ,Humans ,HIV Infections ,medicine.disease_cause ,key population ,0302 clinical medicine ,HIV Infection ,030212 general & internal medicine ,Men having sex with men ,media_common ,education.field_of_study ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Transmission (medicine) ,Infectious Diseases ,AcademicSubjects/MED00290 ,HIV infection, continuum of care, sex, key population, Europe ,Microbiology (medical) ,Population ,Socio-culturale ,03 medical and health sciences ,Acquired immunodeficiency syndrome (AIDS) ,SDG 3 - Good Health and Well-being ,medicine ,media_common.cataloged_instance ,European union ,education ,Pandemics ,continuum of care ,sex ,business.industry ,SARS-CoV-2 ,COVID-19 ,medicine.disease ,030112 virology ,Major Articles and Commentaries ,Anti-Retroviral Agent ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,Demography - Abstract
Background High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. Methods A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. Results We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. Conclusions The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control., Standardized definitions were used to estimate a 4-stage continuum of human immunodeficiency virus (HIV) care in 11 European Union (EU) countries in 2016. The EU is close to the 90-90-90 target, with the main challenge being the percentage of undiagnosed infections.
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- 2020
9. Neurotoxicity with high-dose disulfiram and vorinostat used for HIV latency reversal
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McMahon, J.H., Evans, V.A., Lau, J.S., Symons, J., Zerbato, J.M., Chang, J., Solomon, A., Tennakoon, S., Dantanarayana, A., Hagenauer, M., Lee, S., Palmer, S., Fisher, K., Bumpus, N., Heck, C.J.S., Burger, D.M., Wu, G., Zuck, P., Howell, B.J., Zetterberg, H.H., Blennow, K., Gisslen, M., Rasmussen, T.A., Lewin, S.R., McMahon, J.H., Evans, V.A., Lau, J.S., Symons, J., Zerbato, J.M., Chang, J., Solomon, A., Tennakoon, S., Dantanarayana, A., Hagenauer, M., Lee, S., Palmer, S., Fisher, K., Bumpus, N., Heck, C.J.S., Burger, D.M., Wu, G., Zuck, P., Howell, B.J., Zetterberg, H.H., Blennow, K., Gisslen, M., Rasmussen, T.A., and Lewin, S.R.
- Abstract
Item does not contain fulltext, OBJECTIVE: The aim of this study was to examine whether administering both vorinostat and disulfiram to people with HIV (PWH) on antiretroviral therapy (ART) is well tolerated and can enhance HIV latency reversal. DESIGN: Vorinostat and disulfiram can increase HIV transcription in PWH on ART. Together, these agents may lead to significant HIV latency reversal. METHODS: Virologically suppressed PWH on ART received disulfiram 2000 mg daily for 28 days and vorinostat 400 mg daily on days 8-10 and 22-24. The primary endpoint was plasma HIV RNA on day 11 relative to baseline using a single copy assay. Assessments included cell-associated unspliced RNA as a marker of latency reversal, HIV DNA in CD4+ T-cells, plasma HIV RNA, and plasma concentrations of ART, vorinostat, and disulfiram. RESULTS: The first two participants (P1 and P2) experienced grade 3 neurotoxicity leading to trial suspension. After 24 days, P1 presented with confusion, lethargy, and ataxia having stopped disulfiram and ART. Symptoms resolved by day 29. After 11 days, P2 presented with paranoia, emotional lability, lethargy, ataxia, and study drugs were ceased. Symptoms resolved by day 23. CA-US RNA increased by 1.4-fold and 1.3-fold for P1 and P2 respectively. Plasma HIV RNA was detectable from day 8 to 37 (peak 81 copies ml-1) for P2 but was not increased in P1 Antiretroviral levels were therapeutic and neuronal injury markers were elevated in P1. CONCLUSION: The combination of prolonged high-dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal.
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- 2022
10. Increase of Tryptophan in Serum and in Cerebrospinal Fluid of Patients with HIV Infection During Zidovudine Therapy
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Fuchs, D., Gisslen, M., Larsson, M., Norkrans, G., Hagberg, L., Wachter, H., Filippini, Graziella Allegri, editor, Costa, Carlo V. L., editor, and Bertazzo, Antonella, editor
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- 1996
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11. Brain Injury in COVID-19 is Associated with Autoinflammation and Autoimmunity
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Needham, EJ, Ren, AL, Digby, RJ, Outtrim, JG, Chatfield, DA, Manktelow, AE, Newcombe, VFJ, Doffinger, R, Barcenas-Morales, G, Fonseca, C, Taussig, MJ, Burnstein, RM, Dunai, C, Sithole, N, Ashton, NJ, Zetterberg, H, Gisslen, M, Edén, A, Marklund, E, Griffiths, MJ, Cavanagh, J, Breen, G, Irani, Elmer, A, Kingston, N, Bradley, Taams, LS, Michael, BD, Bullmore, ET, Smith, KGC, Lyons, PA, Coles, AJC, Menon, DK, Group, The Cambridge NeuroCOVID, BioResource, The NIHR COVID-19, Cambridge NIHR Clinical Research Facility, Needham, EJ [0000-0001-7042-7462], Outtrim, JG [0000-0001-8118-6430], Newcombe, VFJ [0000-0001-6044-9035], Sithole, N [0000-0002-8020-223X], Ashton, NJ [0000-0002-3579-8804], Gisslen, M [0000-0002-2357-1020], Irani, SR [0000-0002-7667-9748], and Apollo - University of Cambridge Repository
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the NIHR COVID-19 BioResource ,Cambridge NIHR Clinical Research Facility ,the Cambridge NeuroCOVID Group - Abstract
COVID-19 has been associated with many neurological complications including stroke, delirium and encephalitis. Furthermore, many individuals experience a protracted post-viral syndrome which is dominated by neuropsychiatric symptoms, and is seemingly unrelated to COVID-19 severity. The true frequency and underlying mechanisms of neurological injury are unknown, but exaggerated host inflammatory responses appear to be a key driver of severe COVID-19 more broadly. We sought to investigate the dynamics of, and relationship between, serum markers of brain injury (neurofilament light [NfL], Glial Fibrillary Acidic Protein [GFAP] and total Tau) and markers of dysregulated host response including measures of autoinflammation (proinflammatory cytokines) and autoimmunity. Brain injury biomarkers were measured using the Quanterix Simoa HDx platform, cytokine profiling by Luminex (R&D) and autoantibodies by a custom protein microarray. During hospitalisation, patients with COVID-19 demonstrated elevations of NfL and GFAP in a severity-dependant manner, and there was evidence of ongoing active brain injury at follow-up 4 months later. Raised NfL and GFAP were associated with both elevations of pro-inflammatory cytokines and the presence of autoantibodies; autoantibodies were commonly seen against lung surfactant proteins as well as brain proteins such as myelin associated glycoprotein, but reactivity was seen to a large number of different antigens. Furthermore, a distinct process characterised by elevation of serum total Tau was seen in patients at follow-up, which appeared to be independent of initial disease severity and was not associated with dysregulated immune responses in the same manner as NfL and GFAP.
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- 2021
12. Population pharmacokinetics and pharmacogenetics of ritonavir-boosted darunavir in the presence of raltegravir or tenofovir disoproxil fumarate/emtricitabine in HIV-infected adults and the relationship with virological response:a sub-study of the NEAT001/ANRS143 randomized trial
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Dickinson L., Gurjar R., Stohr W., Bonora S., Owen A., D'Avolio A., Cursley A., Molina J. -M., Faetkenheuer G., Vandekerckhove L., Di Perri G., Pozniak A., Richert L., Raffi F., Boffito M., Dedes N., Chene G., Allavena C., Autran B., Antinori A., Bucciardini R., Vella S., Horban A., Arribas J., Babiker A. G., Pillay D., Franquet X., Schwarze S., Grarup J., Fischer A., Wallet C., Diallo A., Saillard J., Moecklinghoff C., Stellbrink H. -J., Vanleeuwen R., Gatell J., Sandstrom E., Flepp M., Ewings F., George E. C., Hudson F., Pearce G., Quercia R., Rogatto F., Leavitt R., Nguyen B. -Y., Peto T., Goebel F., Marcotullio S., Miller V., Sasieni P., Arnault F., Boucherie C., Jean D., Paniego V., Paraina F., Rouch E., Schwimmer C., Soussi M., Taieb A., Termote M., Touzeau G., Babiker A., Dodds W., Hoppe A., Kummeling I., Pacciarini F., Paton N., Russell C., Taylor K., Ward D., Aagaard B., Eid M., Gey D., Gramjensen B., Jakobsen M. -L., Jansson P. O., Jensen K., Mariajoensen Z., Moseholmlarsen E., Pahl C., Pearson M., Nielsen B. R., Reilev So. S., Christ I., Lathouwers D., Manting C., Van Leeuwen R., Mendy B., Metro A., Couffin-Cadiergues S., Knellwolf A. -L., Palmisiano L., Aznar E., Barea C., Cotarelo M., Esteban H., Girbau I., Moyano B., Ramirez M., Saiz C., Sanchez I., Yllescas M., Binelli A., Colasanti V., Massella M., Anagnostou O., Gioukari V., Touloumi G., Schmied B., Rieger A., Vetter N., Dewit S., Florence E., Gerstoft J., Mathiesen L., Katlama C., Cabie A., Cheret A., Dupon M., Ghosn J., Girard P. -M., Goujard C., Levy Y., Morlat P., Neau D., Obadia M., Perre P., Piroth L., Reynes J., Tattevin P., Ragnaud J. M., Weiss L., Yazdan Y., Yeni P., Zucman D., Esser S., Fatkenheuer G., Hoffmann C., Jessen H., Rockstroh J., Schmidt R., Stephan C., Unger S., Hatzakis A., Daikos G. L., Papadopoulos A., Skoutelis A., Banhegyi D., Mallon P., Mulcahy F., Andreoni M., Castelli F., D'Arminiomonforte A., Diperri G., Galli M., Lazzarin A., Mazzotta F., Torti C., Vullo V., Prins J., Richter C., Verhagen D., Vaneeden A., Doroana M., Antunes F., Maltez F., Sarmento-Castro R., Gonzalez Garcia J., Aldeguer J. L., Clotet B., Domingo P., Gatell J. M., Knobel H., Marquez M., Pilarmiralles M., Portilla J., Soriano V., Tellez M., Thalme A., Blaxhult A., Gisslen M., Winston A., Fox J., Gompels M., Herieka E., Johnson M., Leen C., Teague A., Williams I., Boyd M., Moller N. F., Moseholmlarsen E. F., Lemoing V., Wit F. W. N. M., Kowalska J., Berenguer J., Moreno S., Muller N. J., Torok E., Post F., Angus B., Calvez V., Boucher C., Collins S., Dunn D., Lambert S., Marcelin A. -G., Perno C. F., White E., Ammassari A., Schmidt R. E., Odermarsky M., Smith C., Thiebaut R., Delaserna J. I. B., Castagna A., De Wit S., Furrer H. -J., Mocroft A., Reiss P., Fragola V., Lauriola M., Murri R., Nieuwkerk P., Spire B., Volny-Anne A., West B., Amieva H., Llibre Codina J., Braggion M., Foca E., Dickinson, L., Gurjar, R., Stohr, W., Bonora, S., Owen, A., D'Avolio, A., Cursley, A., Molina, J. -M., Faetkenheuer, G., Vandekerckhove, L., Di Perri, G., Pozniak, A., Richert, L., Raffi, F., Boffito, M., Dedes, N., Chene, G., Allavena, C., Autran, B., Antinori, A., Bucciardini, R., Vella, S., Horban, A., Arribas, J., Babiker, A. G., Pillay, D., Franquet, X., Schwarze, S., Grarup, J., Fischer, A., Wallet, C., Diallo, A., Saillard, J., Moecklinghoff, C., Stellbrink, H. -J., Vanleeuwen, R., Gatell, J., Sandstrom, E., Flepp, M., Ewings, F., George, E. C., Hudson, F., Pearce, G., Quercia, R., Rogatto, F., Leavitt, R., Nguyen, B. -Y., Peto, T., Goebel, F., Marcotullio, S., Miller, V., Sasieni, P., Arnault, F., Boucherie, C., Jean, D., Paniego, V., Paraina, F., Rouch, E., Schwimmer, C., Soussi, M., Taieb, A., Termote, M., Touzeau, G., Babiker, A., Dodds, W., Hoppe, A., Kummeling, I., Pacciarini, F., Paton, N., Russell, C., Taylor, K., Ward, D., Aagaard, B., Eid, M., Gey, D., Gramjensen, B., Jakobsen, M. -L., Jansson, P. O., Jensen, K., Mariajoensen, Z., Moseholmlarsen, E., Pahl, C., Pearson, M., Nielsen, B. R., Reilev, So. S., Christ, I., Lathouwers, D., Manting, C., Van Leeuwen, R., Mendy, B., Metro, A., Couffin-Cadiergues, S., Knellwolf, A. -L., Palmisiano, L., Aznar, E., Barea, C., Cotarelo, M., Esteban, H., Girbau, I., Moyano, B., Ramirez, M., Saiz, C., Sanchez, I., Yllescas, M., Binelli, A., Colasanti, V., Massella, M., Anagnostou, O., Gioukari, V., Touloumi, G., Schmied, B., Rieger, A., Vetter, N., Dewit, S., Florence, E., Gerstoft, J., Mathiesen, L., Katlama, C., Cabie, A., Cheret, A., Dupon, M., Ghosn, J., Girard, P. -M., Goujard, C., Levy, Y., Morlat, P., Neau, D., Obadia, M., Perre, P., Piroth, L., Reynes, J., Tattevin, P., Ragnaud, J. M., Weiss, L., Yazdan, Y., Yeni, P., Zucman, D., Esser, S., Fatkenheuer, G., Hoffmann, C., Jessen, H., Rockstroh, J., Schmidt, R., Stephan, C., Unger, S., Hatzakis, A., Daikos, G. L., Papadopoulos, A., Skoutelis, A., Banhegyi, D., Mallon, P., Mulcahy, F., Andreoni, M., Castelli, F., D'Arminiomonforte, A., Diperri, G., Galli, M., Lazzarin, A., Mazzotta, F., Torti, C., Vullo, V., Prins, J., Richter, C., Verhagen, D., Vaneeden, A., Doroana, M., Antunes, F., Maltez, F., Sarmento-Castro, R., Gonzalez Garcia, J., Aldeguer, J. L., Clotet, B., Domingo, P., Gatell, J. M., Knobel, H., Marquez, M., Pilarmiralles, M., Portilla, J., Soriano, V., Tellez, M., Thalme, A., Blaxhult, A., Gisslen, M., Winston, A., Fox, J., Gompels, M., Herieka, E., Johnson, M., Leen, C., Teague, A., Williams, I., Boyd, M., Moller, N. F., Moseholmlarsen, E. F., Lemoing, V., Wit, F. W. N. M., Kowalska, J., Berenguer, J., Moreno, S., Muller, N. J., Torok, E., Post, F., Angus, B., Calvez, V., Boucher, C., Collins, S., Dunn, D., Lambert, S., Marcelin, A. -G., Perno, C. F., White, E., Ammassari, A., Schmidt, R. E., Odermarsky, M., Smith, C., Thiebaut, R., Delaserna, J. I. B., Castagna, A., De Wit, S., Furrer, H. -J., Mocroft, A., Reiss, P., Fragola, V., Lauriola, M., Murri, R., Nieuwkerk, P., Spire, B., Volny-Anne, A., West, B., Amieva, H., Llibre Codina, J., Braggion, M., Foca, E., Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Global Health, APH - Personalized Medicine, APH - Mental Health, and Medical Psychology
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0301 basic medicine ,Microbiology (medical) ,Adult ,Male ,medicine.medical_specialty ,Anti-HIV Agents ,030106 microbiology ,HIV Infections ,Emtricitabine ,030226 pharmacology & pharmacy ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,immune system diseases ,Internal medicine ,Raltegravir Potassium ,medicine ,Humans ,Pharmacology (medical) ,Tenofovir ,Darunavir ,Constitutive Androstane Receptor ,Pharmacology ,Ritonavir ,biology ,business.industry ,Liver-Specific Organic Anion Transporter 1 ,virus diseases ,Lopinavir ,Viral Load ,Raltegravir ,Multidrug Resistance-Associated Protein 2 ,3. Good health ,NONMEM ,SISTM ,Infectious Diseases ,Pharmacogenetics ,biology.protein ,Female ,SLCO1B1 ,business ,medicine.drug - Abstract
Objectives NEAT001/ANRS143 demonstrated non-inferiority of once-daily darunavir/ritonavir (800/100 mg) + twice-daily raltegravir (400 mg) versus darunavir/ritonavir + tenofovir disoproxil fumarate/emtricitabine (245/200 mg once daily) in treatment-naive patients. We investigated the population pharmacokinetics of darunavir, ritonavir, tenofovir and emtricitabine and relationships with demographics, genetic polymorphisms and virological failure. Methods Non-linear mixed-effects models (NONMEM v. 7.3) were applied to determine pharmacokinetic parameters and assess demographic covariates and relationships with SNPs (SLCO3A1, SLCO1B1, NR1I2, NR1I3, CYP3A5*3, CYP3A4*22, ABCC2, ABCC10, ABCG2 and SCL47A1). The relationship between model-predicted darunavir AUC0–24 and C24 with time to virological failure was evaluated by Cox regression. Results Of 805 enrolled, 716, 720, 347 and 361 were included in the darunavir, ritonavir, tenofovir and emtricitabine models, respectively (11% female, 83% Caucasian). No significant effect of patient demographics or SNPs was observed for darunavir or tenofovir apparent oral clearance (CL/F); coadministration of raltegravir did not influence darunavir or ritonavir CL/F. Ritonavir CL/F decreased by 23% in NR1I2 63396C>T carriers and emtricitabine CL/F was linearly associated with creatinine clearance (P Conclusions Darunavir concentrations were unaltered in the presence of raltegravir and not associated with virological failure. Polymorphisms investigated had little impact on study-drug pharmacokinetics. Darunavir/ritonavir + raltegravir may be an appropriate option for patients experiencing NRTI-associated toxicity.
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- 2020
13. Do people living with HIV experience greater age advancement than their HIV-negative counterparts?
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De Francesco, Davide, Wit, Ferdinand W., Burkle, Alexander, Oehlke, Sebastian, Kootstra, Neeltje A., Winston, Alan, Franceschi, Claudio, Garagnani, Paolo, Pirazzini, Chiara, Libert, Claude, Grune, Tilman, Weber, Daniela, Jansen, Eugene H. J. M., Sabin, Caroline A., Reiss, Peter, Reiss, P., Winston, A., Wit, F. W., Prins, M., van der Loeff, M. F. Schim, Schouten, J., Schmand, B., Geurtsen, G. J., Sharp, D. J., Caan, M. W. A., Majoie, C., Villaudy, J., Berkhout, B., Kootstra, N. A., Gisslen, M., Pasternak, A., Sabin, C. A., Guaraldi, G., Burkle, A., Libert, C., Franceschi, C., Kalsbeek, A., Fliers, E., Hoeijmakers, J., Pothof, J., van der Valk, M., Bisschop, P. H., Portegies, P., Zaheri, S., Burger, D., Cole, J. H., Biirkle, A., Zikkenheiner, W., Janssen, F. R., Underwood, J., Kooij, K. W., van Zoest, R. A., Doyle, N., van der Loeff, M. Schim, Schmand, B. A., Verheij, E., Verboeket, S. O., Elsenga, B. C., Hillebregt, M. M. J., Ruijs, Y. M. C., Benschop, D. P., Tembo, L., McDonald, L., Stott, M., Legg, K., Lovell, A., Erlwein, O., Kingsley, C., Norsworthy, P., Mullaney, S., Kruijer, T., del Grande, L., Olthof, V, Visser, G. R., May, L., Verbraak, F., Demirkaya, N., Visser, I, Majoie, C. B. L. M., Su, T., Leech, R., Huguet, J., Frankin, E., van der Kuyl, A., Weijer, K., Siteur-Van Rijnstra, E., Harskamp-Holwerda, A. M., Maurer, I, Ruiz, M. M. Mangas, Girigorie, A. F., Boeser-Nunnink, B., Kals-Beek, A., Bisschop, P. H. L. T., de Graaff-Teulen, M., Dewaele, S., Garagnani, P., Pirazzini, C., Capri, M., Dall'Olio, F., Chiricolo, M., Salvioli, S., Fuchs, D., Zetterberg, H., Weber, D., Grune, T., Jansen, E. H. J. M., De Francesco, D., Sindlinger, T., Oehlke, S., Global Health, AII - Infectious diseases, APH - Aging & Later Life, Experimental Immunology, ANS - Neurodegeneration, AMS - Restoration & Development, Medical Psychology, and APH - Mental Health
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Male ,0301 basic medicine ,CYTOMEGALOVIRUS ,HIV Infections ,DISEASE ,0302 clinical medicine ,Biomarkers of aging ,Medicine and Health Sciences ,Immunology and Allergy ,030212 general & internal medicine ,the Co-morBidity in Relation to AIDS (COBRA) Collaboration ,POPULATION ,Immunodeficiency ,education.field_of_study ,premature aging ,virus diseases ,11 Medical And Health Sciences ,Middle Aged ,Hepatitis B ,SOUTH-AFRICA ,Infectious Diseases ,Anti-Retroviral Agents ,Cohort ,Female ,Life Sciences & Biomedicine ,medicine.drug ,Adult ,Premature aging ,medicine.medical_specialty ,BIOMARKERS ,Immunology ,Population ,biomarkers of aging ,17 Psychology And Cognitive Sciences ,03 medical and health sciences ,Acquired immunodeficiency syndrome (AIDS) ,Virology ,ddc:570 ,Internal medicine ,medicine ,Humans ,accelerated aging ,education ,Aged ,accelerated aging, aging, biological age, biomarkers of aging, HIV, premature aging ,Science & Technology ,business.industry ,aging ,Biology and Life Sciences ,HIV ,06 Biological Sciences ,medicine.disease ,COMORBIDITIES ,biological age ,INFECTED INDIVIDUALS ,IMMUNOGLOBULIN-G ANTIBODY ,PROTEASE INHIBITORS ,Cross-Sectional Studies ,030104 developmental biology ,RISK-FACTORS ,business ,Saquinavir - Abstract
Objectives: Despite successful antiretroviral (ARV) therapy, people living with HIV (PLWH) may show signs of premature/accentuated aging. We compared established biomarkers of aging in PLWH, appropriately-chosen HIV-negative individuals, and blood donors, and explored factors associated with biological age advancement.Design: Cross-sectional analysis of 134 PLWH on suppressive ARV therapy, 79 lifestyle-comparable HIV-negative controls aged ≥45 years from the Co-morBidity in Relation to AIDS (COBRA) cohort, and 35 age-matched blood donors (BD).Methods: Biological age was estimated using a validated algorithm based on ten biomarkers. Associations between ‘age advancement’ (biological minus chronological age) and HIV status/parameters, lifestyle, cytomegalovirus (CMV), hepatitis B (HBV) and hepatitis C virus (HCV) infections were investigated using linear regression.Results: The average (95% CI) age advancement was greater in both HIV-positive [13.2 (11.6, 14.9) years] and HIV-negative [5.5 (3.8, 7.2) years] COBRA participants compared to BD [-7.0 (-4.1, -9.9) years, both p's < 0.001)], but also in HIV-positive compared to HIV-negative participants (p < 0.001). Chronic HBV, higher anti-CMV IgG titer and CD8+ T-cell count were each associated with increased age advancement, independently of HIV-status/group. Among HIV-positive participants, age advancement was increased by 3.5 (0.1, 6.8) years among those with nadir CD4+ < 200 cells/μL and by 0.1 (0.06, 0.2) years for each additional month of exposure to saquinavir.Conclusions: Both treated PLWH and lifestyle-comparable HIV-negative individuals show signs of age advancement compared to BD, to which persistent CMV, HBV co-infection and CD8+ T-cell activation may have contributed. Age advancement remained greatest in PLWH and was related to prior immunodeficiency and cumulative saquinavir exposure. published
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- 2019
14. Response to: ‘How helpful are the European AIDS Clinical Society cognitive screening questions in predicting cognitive impairment in an aging, well‐treated HIV‐positive population?’
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Winston, A, primary, Cotter, A, additional, Gisslen, M, additional, Mallon, PWG, additional, and Cinque, P, additional
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- 2020
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15. Cerebrospinal Fluid Antibodies Directed against Neuron-Associated Gangliosides in HIV-1 Infection
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Gisslen, M., Lekman, A., and Fredman, P.
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Cerebrospinal fluid -- Medical examination ,HIV infection -- Development and progression ,Health - Abstract
Byline: M. Gisslen (1), A. Lekman (2), P. Fredman (2) Keywords: Key Words HIV-1; Cerebrospinal fluid; Anti-ganglioside antibodies; Neuron Abstract: Background: Loss of synapses and neurons is a common finding in HIV-1 infection. Since the in vivo infection of neurons by HIV-1 is limited, indirect factors are likely to contribute to the pathogenesis. Patients and Methods: We have analyzed cerebrospinal fluid (CSF) and serum samples from 25 HIV-1-infected individuals (nine with and 16 without CNS complications) and 19 HIV-negative controls with aseptic meningitis or viral encephalitis, for the presence of antibodies directed against the neuron-associated gangliosides GM1, GD1a and GD1b. Results: Positive antibody titers to aY= 1 of the gangliosides were found in 13/25 HIV-1-infected patients in CSF and in 17/25 in serum. Significant correlations were found between the presence and titers of CSF antibodies against GM1, GD1a, and GD1b. Six out of nine patients with, and 3/16 without neurological complications (p < 0.05) had positive CSF titers of aY= 1 of the ganglioside antibodies combined with negative serum titers, indicating intrathecal antibody production. In contrast, only 1/19 controls had detectable anti-ganglioside antibodies in the CSF. Conclusion: The results should be interpreted with caution and CSF anti-ganglioside antibody production might be a part of a non-specific intrathecal polyclonal immunoactivation. Nevertheless, autoantibodies directed against neuron-associated gangliosides might be involved in the neuropathogenesis in HIV-1 disease. Author Affiliation: (1) Institute of Internal Medicine, Dept. of Infectious Diseases, Sahlgrenska University Hospital, S-416 85 Goteborg, Sweden Phone: +46-31-3434000, Fax: +46-31-847813, e-mail: magnus.gisslen@infect.gu.se, SE (2) Institute of Clinical Neuroscience, Dept. of Psychiatry and Neurochemistry, Sahlgrenska University Hospital, Goteborg, Sweden, SE Article note: Received: September 1, 1999 * Revision accepted: February 29, 2000
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- 2000
16. Validation of a Novel Multivariate Method of Defining HIV-Associated Cognitive Impairment
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Underwood, J, de Francesco, D, Cole, JH, Caan, MWA, van Zoest, RA, Schmand, BA, Sharp, DJ, Sabin, CA, Reiss, P, Winston, A, Wit, FWNM, Schouten, J, Kooij, KW, Elsenga, BC, Janssen, FR, Heidenrijk, M, Zikkenheiner, W, van der Valk, M, Kootstra, NA, Harskamp-Holwerda, AM, Maurer, I, Ruiz, MMM, Girigorie, AF, Villaudy, J, Frankin, E, Pasternak, A, Berkhout, B, van der Kuyl, T, Portegies, P, Geurtsen, GJ, ter Stege, JA, Twennaar, MK, Majoie, CBLM, Su, T, Weijer, K, Bisschop, PHLT, Kalsbeek, A, Wezel, M, Visser, I, Ruhe, HG, Franceschi, C, Garagnani, P, Pirazzini, C, Capri, M, Dall'Olio, F, Chiricolo, M, Salvioli, S, Hoeijmakers, J, Pothof, J, Prins, M, Martens, M, Moll, S, Berkel, J, Totte, M, Kovalev, S, Gisslen, M, Fuchs, D, Zetterberg, H, McDonald, L, Stott, M, Legg, K, Lovell, A, Erlwein, O, Doyle, N, Kingsley, C, Leech, R, Zaheri, S, Hillebregt, MMJ, Ruijs, YMC, Benschop, DP, Burger, D, de Graaff-Teulen, M, Guaraldi, G, Buerkle, A, Sindlinger, T, Moreno-Villanueva, M, Keller, A, Sabin, C, Libert, C, Dewaele, S, Boffito, M, Mallon, P, Post, F, Sachikonye, M, Anderson, J, Asboe, D, Garvey, L, Pozniak, A, Vera, J, Williams, I, Campbell, L, Yurdakul, S, Okumu, S, Pollard, L, Otiko, D, Phillips, L, Laverick, R, Fisher, M, Clarke, A, Bexley, A, Richardson, C, Macken, A, Ghavani-Kia, B, Maher, J, Byrne, M, Flaherty, A, Mguni, S, Clark, R, Nevin-Dolan, R, Pelluri, S, Johnson, M, Ngwu, N, Hemat, N, Jones, M, Carroll, A, Whitehouse, A, Burgess, L, Babalis, D, Higgs, C, Seah, E, Fletcher, S, Anthonipillai, M, Moyes, A, Deats, K, Syed, I, Matthews, C, Underwood, J, de Francesco, D, Cole, JH, Caan, MWA, van Zoest, RA, Schmand, BA, Sharp, DJ, Sabin, CA, Reiss, P, Winston, A, Wit, FWNM, Schouten, J, Kooij, KW, Elsenga, BC, Janssen, FR, Heidenrijk, M, Zikkenheiner, W, van der Valk, M, Kootstra, NA, Harskamp-Holwerda, AM, Maurer, I, Ruiz, MMM, Girigorie, AF, Villaudy, J, Frankin, E, Pasternak, A, Berkhout, B, van der Kuyl, T, Portegies, P, Geurtsen, GJ, ter Stege, JA, Twennaar, MK, Majoie, CBLM, Su, T, Weijer, K, Bisschop, PHLT, Kalsbeek, A, Wezel, M, Visser, I, Ruhe, HG, Franceschi, C, Garagnani, P, Pirazzini, C, Capri, M, Dall'Olio, F, Chiricolo, M, Salvioli, S, Hoeijmakers, J, Pothof, J, Prins, M, Martens, M, Moll, S, Berkel, J, Totte, M, Kovalev, S, Gisslen, M, Fuchs, D, Zetterberg, H, McDonald, L, Stott, M, Legg, K, Lovell, A, Erlwein, O, Doyle, N, Kingsley, C, Leech, R, Zaheri, S, Hillebregt, MMJ, Ruijs, YMC, Benschop, DP, Burger, D, de Graaff-Teulen, M, Guaraldi, G, Buerkle, A, Sindlinger, T, Moreno-Villanueva, M, Keller, A, Sabin, C, Libert, C, Dewaele, S, Boffito, M, Mallon, P, Post, F, Sachikonye, M, Anderson, J, Asboe, D, Garvey, L, Pozniak, A, Vera, J, Williams, I, Campbell, L, Yurdakul, S, Okumu, S, Pollard, L, Otiko, D, Phillips, L, Laverick, R, Fisher, M, Clarke, A, Bexley, A, Richardson, C, Macken, A, Ghavani-Kia, B, Maher, J, Byrne, M, Flaherty, A, Mguni, S, Clark, R, Nevin-Dolan, R, Pelluri, S, Johnson, M, Ngwu, N, Hemat, N, Jones, M, Carroll, A, Whitehouse, A, Burgess, L, Babalis, D, Higgs, C, Seah, E, Fletcher, S, Anthonipillai, M, Moyes, A, Deats, K, Syed, I, and Matthews, C
- Abstract
BACKGROUND: The optimum method of defining cognitive impairment in virally suppressed people living with HIV is unknown. We evaluated the relationships between cognitive impairment, including using a novel multivariate method (NMM), patient- reported outcome measures (PROMs), and neuroimaging markers of brain structure across 3 cohorts. METHODS: Differences in the prevalence of cognitive impairment, PROMs, and neuroimaging data from the COBRA, CHARTER, and POPPY cohorts (total n = 908) were determined between HIV-positive participants with and without cognitive impairment defined using the HIV-associated neurocognitive disorders (HAND), global deficit score (GDS), and NMM criteria. RESULTS: The prevalence of cognitive impairment varied by up to 27% between methods used to define impairment (eg, 48% for HAND vs 21% for NMM in the CHARTER study). Associations between objective cognitive impairment and subjective cognitive complaints generally were weak. Physical and mental health summary scores (SF-36) were lowest for NMM-defined impairment ( P < .05).There were no differences in brain volumes or cortical thickness between participants with and without cognitive impairment defined using the HAND and GDS measures. In contrast, those identified with cognitive impairment by the NMM had reduced mean cortical thickness in both hemispheres ( P < .05), as well as smaller brain volumes ( P < .01). The associations with measures of white matter microstructure and brain-predicted age generally were weaker. CONCLUSION: Different methods of defining cognitive impairment identify different people with varying symptomatology and measures of brain injury. Overall, NMM-defined impairment was associated with most neuroimaging abnormalities and poorer self-reported health status. This may be due to the statistical advantage of using a multivariate approach.
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- 2019
17. Pol gene variation in Swedish HIV-2 patients failing antiretroviral therapy
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Brandin, E, Lindborg, L, Gyllensten, K, Broström, C, Hagberg, L, Gisslen, M, Tuvesson, B, Blaxhult, A, and Albert, J
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- 2003
18. Blood Telomere Length Changes After Ritonavir-Boosted Darunavir Combined With Raltegravir or Tenofovir-Emtricitabine in Antiretroviral-Naive Adults Infected With HIV-1
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STELLA-ASCARIZ, N., MONTEJANO, R., RODRIGUEZ-CENTENO, J., ALEJOS, B., Schwimmer, Christine, BERNARDINO, J. I., RODES, B., Allavena, C., Hoffmann, C., GISSLEN, M., De Miguel, R., ESTEBAN-CANTOS, A., Wallet, Cedrick, Raffi, F., ARRIBAS, J. R., Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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PharmacoEpi-Drugs ,immune system diseases ,virus diseases ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie - Abstract
Background. Tenofovir is a potent inhibitor of human telomerase. The clinical relevance of this inhibition is unknown. Methods. NEAT001/ANRS143 is a randomized trial that showed noninferiority over 96 weeks of ritonavir-boosted darunavir plus raltegravir versus tenofovir disoproxil fumarate/emtricitabine in 805 antiretroviral antiretrovrial-naive HIV-infected adults. We compared changes in whole-blood telomere length measured with quantitative polymerase chain reaction in 201 randomly selected participants (104 raltegravir and 97 tenofovir disoproxil fumarate/emtricitabine). We performed multivariable estimative and predictive linear regression. Results. At week 96, participants receiving tenofovir disoproxil fumarate/emtricitabine had a statistically significant higher gain in telomere length than participants receiving raltegravir. Difference in mean telomere length change between groups (tenofovir disoproxil fumarate/emtricitabine minus raltegravir) from baseline to week 96 adjusted by baseline telomere length was 0.031 (P = .009). This difference was not significantly confounded by age, gender, known duration of HIV infection, CD4 (baseline/nadir), CD8 cells, CD4/CD8 ratio, HIV viral load (baseline/week 96), tobacco and alcohol consumption, statins, or hepatitis C. Conclusion. Antiretroviral-naive HIV-infected adults receiving ritonavir-boosted darunavir and tenofovir disoproxil fumarate/emtricitabine had a significant higher gain in blood telomere length than those receiving ritonavir-boosted darunavir and raltegravir, suggesting a better initial recovery from HIV-associated immunosenescence.
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- 2018
19. Cerebrospinal Fluid Abacavir Concentrations in HIV-positive Patients Following Once-daily Administration
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Calcagno, A., Pinnetti, C., De Nicolò, A., Scarvaglieri, E., Gisslen, M., Tempestilli, M., D'Avolio, A., Fedele, V., Di Perri, G., Antinori, A., and Bonora, S.
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Adult ,Male ,Time Factors ,Anti-HIV Agents ,abacavir ,protease inhibitors ,virus diseases ,HIV Infections ,Middle Aged ,central nervous system ,Dideoxynucleosides ,Drug Administration Schedule ,cerebrospinal fluid ,age ,pharmacokinetics ,Treatment Outcome ,Short Reports ,Italy ,immune system diseases ,Tandem Mass Spectrometry ,Humans ,Female ,Drug Monitoring ,Chromatography, High Pressure Liquid - Abstract
Abacavir is a widely used nucleotide reverse transcriptase inhibitor, for which cerebrospinal fluid (CSF) exposure has been previously assessed in twice‐daily recipients. We studied abacavir CSF concentrations in 61 and nine HIV‐positive patients taking abacavir once daily and twice daily, respectively. Patients on once‐daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng ml(−1), P = 0.038 and 123 vs. 49 ng ml(−1), P = 0.038) but similar CSF‐to‐plasma ratios (0.8 vs. 0.5, P = 0.500). CSF abacavir concentrations were adequate in patients receiving once‐daily treatment.
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- 2018
20. Cerebrospinal fluid abacavir concentrations in HIV-positive patients following once-daily administration
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Calcagno, A., primary, Pinnetti, C., additional, De Nicolò, A., additional, Scarvaglieri, E., additional, Gisslen, M., additional, Tempestilli, M., additional, D'Avolio, A., additional, Fedele, V., additional, Di Perri, G., additional, Antinori, A., additional, and Bonora, S., additional
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- 2018
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21. Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy
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Winston, A, Stohr, W, Antinori, A, Arenas Pinto, A, Llibre, J, Amieva, H, Cabie, A, Williams, I, Di Perri, G, Tellez, M, Rockstroh, J, Babiker, A, Pozniak, A, Raffi, F, Richert, L, Dedes, N, Chene, G, Allavena, C, Autran, B, Bucciardini, R, Vella, S, Horban, A, Arribas, J, Boffito, M, Pillay, D, Franquet, X, Schwarze, S, Grarup, J, Fischer, A, Wallet, C, Diallo, A, Molina, J, Saillard, J, Moecklinghoff, C, Stellbrink, H, Leeuwen, R, Gatell, J, Sandstrom, E, Flepp, M, Ewings, F, George, E, Hudson, F, Pearce, G, Quercia, R, Rogatto, F, Leavitt, R, Nguyen, B, Goebel, F, Marcotullio, S, Kaur, N, Sasieni, P, Spencer Drake, C, Peto, T, Miller, V, Arnault, F, Boucherie, C, Jean, D, Paniego, V, Rouch, E, Schwimmer, C, Soussi, M, Taieb, A, Termote, M, Touzeau, G, Cursley, A, Dodds, W, Hoppe, A, Kummeling, I, Pacciarini, F, Paton, N, Russell, C, Taylor, K, Ward, D, Aagaard, B, Eid, M, Gey, D, Jensen, B, Jakobsen, M, Jansson, P, Jensen, K, Joensen, Z, Larsen, E, Pahl, C, Pearson, M, Nielsen, B, Reilev, S, Christ, I, Lathouwers, D, Manting, C, Mendy, B, Metro, A, Couffin Cadiergues, S, Knellwolf, A, Palmisiano, L, Aznar, E, Barea, C, Cotarelo, M, Esteban, H, Girbau, I, Moyano, B, Ramirez, M, Saiz, C, Sanchez, I, Yllescas, M, Binelli, A, Colasanti, V, Massella, M, Anagnostou, O, Gioukari, V, Touloumi, G, Schmied, B, Rieger, A, Vetter, N, Wit, S, Florence, E, Vandekerckhove, L, Gerstoft, J, Mathiesen, L, Katlama, C, Cheret, A, Dupon, M, Ghosn, J, Girard, P, Goujard, C, Levy, Y, Morlat, P, Neau, D, Obadia, M, Perre, P, Piroth, L, Reynes, J, Tattevin, P, Ragnaud, J, Weiss, L, Yazdan, Y, Yeni, P, Zucman, D, Behrens, G, Esser, S, Fatkenheuer, G, Hoffmann, C, Jessen, H, Schmidt, R, Stephan, C, Unger, S, Hatzakis, A, Daikos, G, Papadopoulos, A, Skoutelis, A, Banhegyi, D, Mallon, P, Mulcahy, F, Andreoni, M, Bonora, S, Castelli, F, Monforte, A, Galli, M, Lazzarin, A, Mazzotta, F, Carlo, T, Vullo, V, Prins, J, Richter, C, Verhagen, D, Eeden, A, Doroana, M, Antunes, F, Maltez, F, Sarmento Castro, R, Garcia, J, Aldeguer, J, Clotet, B, Domingo, P, Knobel, H, Marquez, M, Miralles, M, Portilla, J, Soriano, V, Thalme, A, Blaxhult, A, Gisslen, M, Fox, J, Gompels, M, Herieka, E, Johnson, M, Leen, C, Teague, A, Boyd, M, Moller, N, Frosig, E, Moing, V, Wit, F, Kowalska, J, Berenguer, J, Moreno, S, Muhller, N, Torok, E, Post, F, Angus, B, Calvez, V, Boucher, C, Collins, S, Dunn, D, Lambert, S, Marcelin, A, Perno, Cf, White, E, Ammassari, A, Stoehr, W, Odermarsky, M, Smith, C, Thiebaut, R, Laserna, B, Castagna, A, Furrer, H, Mocroft, A, Reiss, P, Fragola, V, Lauriola, M, Murri, R, Nieuwkerk, P, Spire, B, Volny Anne, A, West, B, Maria, J, Braggion, M, Foca, E, Amsterdam institute for Infection and Immunity, Infectious diseases, Global Health, Amsterdam Public Health, Medical Psychology, Winston, A., Stohr, W., Antinori, A., Arenas-Pinto, A., Llibre, J. M., Amieva, H., Cabie, A., Williams, I., Di Perri, G., Tellez, M. J., Rockstroh, J., Babiker, A., Pozniak, A., Raffi, F., Richert, L., on beahlf of NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 Study, Group, and Castagna, A.
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Gerontology ,Male ,Antiretroviral naïve ,antiretroviral naïve ,HIV Infections ,0302 clinical medicine ,HIV ,antiretroviral naïve ,cognitive ,neuropsychological tests ,Interquartile range ,Verbal fluency test ,HIV Infection ,Pharmacology (medical) ,030212 general & internal medicine ,Sida ,Psychomotor learning ,education.field_of_study ,biology ,NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 Study Group ,Health Policy ,Cognition ,Middle Aged ,Settore MED/07 - Microbiologia e Microbiologia Clinica ,Cognitive test ,Cognitive ,Neuropsychological tests ,Infectious Diseases ,Europe ,Anti-Retroviral Agents ,Population study ,Female ,Human ,Adult ,medicine.medical_specialty ,Population ,03 medical and health sciences ,Virology ,Internal medicine ,medicine ,Humans ,Cognitive Dysfunction ,Psychological Tests ,education ,business.industry ,1103 Clinical Sciences ,biology.organism_classification ,Psychological Test ,neuropsychological test ,Anti-Retroviral Agent ,business ,030217 neurology & neurosurgery - Abstract
OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naive HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study.METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models.RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/μL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA.CONCLUSIONS: In this large, European-wide, ART-naive population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors. (Less)
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- 2016
22. Bone mineral density and inflammatory and bone biomarkers after darunavir-ritonavir combined with either raltegravir or tenofovir-emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of the NEAT001/ANRS143 randomised trial
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Bernardino, J. I., Mocroft, A., Mallon, P. W., Wallet, C., Gerstoft, J., Russell, C., Reiss, P., Katlama, C., De Wit, S., Richert, L., Babiker, A., Buno, A., Castagna, A., Girard, P. -M., Chene, G., Raffi, F., Arribas, J. R., Dedes, N, Chene, G, Richert, L, Allavena, C, Raffi, F, Autran, B, Antinori, A, Bucciardini, R, Vella, S, Horban, A, Arribas, J, Babiker, Ag, Boffito, M, Pillay, D, Pozniak, A, Franquet, X, Schwarze, S, Grarup, J, Fischer, A, Wallet, C, Diallo, A, Molina, Jm, Saillard, J, Moecklinghoff, C, Stellbrink, Hj, Van Leeuwen, R, Gatell, J, Sandstrom, E, Flepp, M, Ewings, F, George, Ec, Hudson, F, Pearce, G, Quercia, R, Rogatto, F, Leavitt, R, Nguyen, By, Goebel, F, Marcotullio, S, Babiker, A, Kaur, N, Sasieni, P, Spencer-Drake, C, Peto, T, Miller, V, Chêne, G, Arnault, F, Boucherie, C, Jean, D, Paniego, V, Paraina, F, Rouch, E, Schwimmer, C, Soussi, M, Taieb, A, Termote, M, Touzeau, G, Cursley, A, Dodds, W, Hoppe, A, Kummeling, I, Pacciarini, F, Paton, N, Russell, C, Taylor, K, Ward, D, Aagaard, B, Eid, M, Gey, D, Jensen, Bg, Jakobsen, Ml, Jansson, Po, Jensen, K, Joensen, Zm, Larsen, Em, Pahl, C, Pearson, M, Nielsen, Br, Reilev, Ss, Christ, I, Lathouwers, D, Mendy, By, Metro, A, Couffin-Cadiergues, S, Knellwolf, Al, Palmisiano, L, Aznar, E, Barea, C, Cotarelo, M, Esteban, H, Girbau, I, Moyano, B, Ramirez, M, Saiz, C, Sanchez, I, Yllescas, M, Binelli, A, Colasanti, V, Massella, M, Anagnostou, O, Gioukari, V, Touloumi, G, Schmied, B, Rieger, A, Vetter, N, De Wit, S, Florence, E, Vandekerckhove, L, Gerstoft, J, Mathiesen, L, Katlama, C, Cabie, A, Cheret, A, Dupon, M, Ghosn, J, Girard, Pm, Goujard, C, Lévy, Y, Morlat, P, Neau, D, Obadia, M, Perre, P, Piroth, L, Reynes, J, Tattevin, P, Ragnaud, Jm, Weiss, L, Yazdan, Y, Yeni, P, Zucman, D, Behrens, G, Esser, S, Fätkenheuer, G, Hoffmann, C, Jessen, H, Rockstroh, J, Schmidt, R, Stephan, C, Unger, S, Hatzakis, A, Daikos, Gl, Papadopoulos, A, Skoutelis, A, Banhegyi, D, Mallon, P, Mulcahy, F, Andreoni, M, Bonora, S, Castelli, F, Monforte, Ad, Di Perri, G, Galli, M, Lazzarin, A, Mazzotta, F, Carlo, T, Vullo, V, Prins, J, Richter, C, Verhagen, D, Van Eeden, A, Doroana, M, Antunes, F, Maltez, F, Sarmento-Castro, R, Gonzalez Garcia, J, López Aldeguer, J, Clotet, B, Domingo, P, Gatell, Jm, Knobel, H, Marquez, M, Pilar Miralles, M, Portilla, J, Soriano, V, Tellez, Mj, Thalme, A, Blaxhult, A, Gisslen, M, Winston, A, Fox, J, Gompels, M, Herieka, E, Johnson, M, Leen, C, Teague, A, Williams, I, Boyd, Ma, Møller, Nf, Frøsig, E, Larsen, M, Le Moing, V, Wit, Fw, Kowalska, J, Berenguer, J, Moreno, S, Müller, Nj, Török, E, Post, F, Angus, B, Calvez, V, Boucher, C, Collins, S, Dunn, D, Lambert, S, Marcelin, Ag, Perno, Cf, White, E, Ammassari, A, Stoehr, W, Schmidt, Re, Odermarsky, M, Smith, C, Thiébaut, R, De La Serna JI, Castagna, A, Furrer, Hj, Mocroft, A, Reiss, P, Fragola, V, Lauriola, M, Murri, R, Nieuwkerk, P, Spire, B, Volny-Anne, A, West, B, Amieva, H, Codina, Jm, Braggion, Marco, Focà, E, Bernardino Jose, I., Mocroft, Amanda, Mallon Patrick, W., Wallet, Cedrick, Gerstoft, Jan, Russell, Charlotte, Reiss, Peter, Katlama, Christine, De Wit, Stephane, Richert, Laura, Babiker, Abdel, Buno, Antonio, Castagna, Antonella, Girard Pierre, Marie, Chene, Genevieve, Raffi, Francoi, Arribas Jose, R., AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Infectious diseases, and Medical Psychology
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Male ,Bone density ,Epidemiology ,Infectious Diseases ,Immunology ,Virology ,Osteoporosis ,HIV Infections ,Comorbidity ,Absorptiometry, Photon ,Bone Density ,Emtricitabine ,Darunavir ,Middle Aged ,Viral Load ,Photon ,Europe ,Osteopetrosis ,Combination ,Drug Therapy, Combination ,Female ,Bone Diseases ,medicine.drug ,Adult ,medicine.medical_specialty ,Anti-HIV Agents ,Biomarkers ,Bone Diseases, Metabolic ,CD4 Lymphocyte Count ,Humans ,Inflammation ,Raltegravir Potassium ,Ritonavir ,Tenofovir ,Tenofovir alafenamide ,Drug Therapy ,Internal medicine ,medicine ,Absorptiometry ,business.industry ,Abacavir/Lamivudine ,Raltegravir ,medicine.disease ,Surgery ,Osteopenia ,Regimen ,Metabolic ,business - Abstract
Osteopenia, osteoporosis, and low bone mineral density are frequent in patients with HIV. We assessed the 96 week loss of bone mineral density associated with a nucleoside or nucleotide reverse transcriptase inhibitor (NtRTI)-sparing regimen. Antiretroviral-naive adults with HIV were enrolled in 78 clinical sites in 15 European countries into a randomised (1:1), open-label, non-inferiority trial (NEAT001/ANRS143) assessing the efficacy and safety of darunavir (800 mg once per day) and ritonavir (100 mg once per day) plus either raltegravir (400 mg twice per day; NtRTI-sparing regimen) or tenofovir (245 mg once per day) and emtricitabine (200 mg once per day; standard regimen). For this bone-health substudy, 20 of the original sites in six countries participated, and any patient enrolled at one of these sites who met the following criteria was eligible: plasma viral loads greater than 1000 HIV RNA copies per mL and CD4 cell counts of fewer than 500 cells per μL, except in those with symptomatic HIV infection. Exclusion criteria included treatment for malignant disease, testing positive for hepatitis B virus surface antigen, pregnancy, creatinine clearance less than 60 mL per min, treatment for osteoporosis, systemic steroids, or oestrogen-replacement therapy. The two primary endpoints were the mean percentage changes in lumbar spine and total hip bone mineral density at week 48, assessed by dual energy x-ray absorptiometry (DXA) scans. We did the analysis with an intention-to-treat-exposed approach with antiretroviral modifications ignored. The parent trial is registered with ClinicalTrials.gov, number NCT01066962, and is closed to new participants. Between Aug 2, 2010, and April 18, 2011, we recruited 146 patients to the substudy, 70 assigned to the NtRTI-sparing regimen and 76 to the standard regimen. DXA data were available for 129, 121 and 107 patients at baseline, 48 and 96 weeks respectively. At week 48, the mean percentage loss in bone mineral density in the lumbar spine was greater in the standard group than in the NtRTI-sparing group (mean percentage change -2.49% vs -1.00%, mean percentage difference -1.49, 95% CI -2.94 to -0.04; p=0.046). Total hip bone mineral density loss was similarly greater at week 48 in the standard group than in the NtRTI-sparing group (mean percentage change -3.30% vs -0.73%; mean percentage difference -2.57, 95% CI -3.75 to -1.35; p
- Published
- 2015
23. Asymptomatic cerebrospinal fluid viral escape during ART is associated with increased intrathecal immune activation
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Eden, A., primary, Nilsson, S., additional, Hagberg, L., additional, Fuchs, D., additional, Zetterberg, H., additional, Svennerholm, B., additional, and Gisslen, M., additional
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- 2015
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24. THU-395 - Lower risk of multiple sclerosis in patients with chronic hepatitis C: A nationwide population-based register study 2001-2013
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Söderholm, J., Yilmaz, A., Buesch, K., Wejstál, R., Brolund, A., Kövamees, J., Sällberg, M., Lagging, M., and Gisslén, M.
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- 2018
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25. Swedish Covid-19 Investigation for Future Insights – A Population Epidemiology Approach Using Register Linkage (SCIFI-PEARL)
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Nyberg F, Franzén S, Lindh M, Vanfleteren L, Hammar N, Wettermark B, Sundström J, Santosa A, Björck S, and Gisslén M
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sars-cov-2 population cohort data updates observational research longitudinal ,Infectious and parasitic diseases ,RC109-216 - Abstract
Fredrik Nyberg,1 Stefan Franzén,1,2 Magnus Lindh,3,4 Lowie Vanfleteren,5,6 Niklas Hammar,7 Björn Wettermark,8 Johan Sundström,9,10 Ailiana Santosa,1 Staffan Björck,11 Magnus Gisslén3,12 1School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2National Diabetes Register, Centre of Registers Västra Götaland, Gothenburg, Sweden; 3Department of Infectious Diseases, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 4Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden; 5COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, Sweden; 6Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 7Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden; 8Pharmacoepidemiology & Social Pharmacy, Department of Pharmacy, Uppsala University, Uppsala, Sweden; 9Clinical Epidemiology Unit, Department of Medical Sciences, Uppsala University, Uppsala, Sweden; 10The George Institute for Global Health, University of New South Wales, Sydney, Australia; 11Centre of Registers Västra Götaland, Gothenburg, Sweden; 12Region Västra Götaland, Department of Infectious Diseases, Sahlgrenska University Hospital, Gothenburg, SwedenCorrespondence: Fredrik NybergSchool of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Box 463, Gothenburg, 405 30, SwedenTel +46 31 7866289; +46 76 6186289Email Fredrik.Nyberg.2@gu.seBackground: In response to the Covid-19 pandemic, we designed and initiated a nationwide linked multi-register, regularly updated, observational study for timely response to urgent scientific questions.Aim: To describe the SCIFI-PEARL (Swedish Covid-19 Investigation for Future Insights – a Population Epidemiology Approach using Register Linkage) linked database encompassing essentially all known diagnosed Swedish Covid-19 patients plus a large general population comparison cohort and outline its utility in the current and future phases of the pandemic.Methods: Individuals with Covid-19 from the entire country are identified on a regularly updated basis, from different sources: all individuals from SmiNet, the national database of notifiable diseases, with positive SARS-CoV-2 polymerase chain reaction (PCR) test results; patients identified in the healthcare system by condition (ICD-10) or procedure codes in the National Patient Register or Cause-of-Death Register; patients identified through several disease-specific national quality registers (NQRs); and in two regions additionally patients identified in primary care. A comparison population was obtained by stratified random sampling from Swedish national population registers. Data from all these registers plus the National Prescribed Drug Register, the Cancer Register, national sociodemographic registers, some additional NQRs, the National Vaccination Register, and further data sources, are then linked to all study subjects (Covid-19 cases and population cohort). New cases in the study population and all data for all subjects are updated every few months, as required.Conclusion and Utility: The SCIFI-PEARL study cohort captures Swedish residents with Covid-19 on an ongoing basis, includes a representative general population comparison cohort, and links to a broad range of national and regional healthcare data for a comprehensive longitudinal view of the Covid-19 pandemic. By combining high-quality national registers with short time delay and continuous repeated linkage and updating, the project brings timely and internationally relevant data for epidemiological research on SARS-CoV-2. Our efforts provide an example and important learnings for similar efforts internationally in the future.Keywords: SARS-CoV-2, population cohort, data updates, observational research, longitudinal
- Published
- 2021
26. Laboratory diagnostic value of neopterin measurements in patients with COVID-19 infection
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Fuchs Dietmar and Gisslen Magnus
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covid-19 ,neopterin ,laboratory diagnostic ,Crystallography ,QD901-999 - Abstract
The new coronavirus SARS-CoV-2 was identified to be responsible for the COVID-19 pandemic. There are striking differences in the response to infection, some people develop no or mild symptoms, while other outcomes are severe of even fatal. For those COVID-19 patients who require hospitalization, prognostic markers could help clinicians to identify patients with a poor outcome early. The serum levels of the immune activation marker neopterin have already been shown to be of prognostic value in patients with SARS-CoV-1 and a similar pattern can be observed for SARS-CoV-2. This comment discusses the biochemical circuits that support the clinical value of neopterin measurements in COVID-19 patients.
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- 2021
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27. Cerebrospinal Fluid and Neuroimaging Biomarker Abnormalities Suggest Early Neurological Injury in a Subset of Individuals During Primary HIV Infection
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Peluso, M. J., primary, Meyerhoff, D. J., additional, Price, R. W., additional, Peterson, J., additional, Lee, E., additional, Young, A. C., additional, Walter, R., additional, Fuchs, D., additional, Brew, B. J., additional, Cinque, P., additional, Robertson, K., additional, Hagberg, L., additional, Zetterberg, H., additional, Gisslen, M., additional, and Spudich, S., additional
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- 2013
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28. Persistent enterocyte damage despite decreased microbial translocation in patients on effective antiretroviral therapy
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Nowak, P, primary, Vesterbacka, J, additional, Barqasho, B, additional, Funaoka, H, additional, Kanda, T, additional, Gisslen, M, additional, and Sönnerborg, A, additional
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- 2012
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29. Antiretroviral drug treatment of CNS HIV-1 infection
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Yilmaz, A., primary, Price, R. W., additional, and Gisslen, M., additional
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- 2011
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30. Reply to Seligman
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Eden, A., primary, Fuchs, D., additional, Hagberg, L., additional, Nilsson, S., additional, Spudich, S., additional, Svennerholm, B., additional, Price, R. W., additional, and Gisslen, M., additional
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- 2011
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31. Biomarkers of HIV-1 CNS infection and injury
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Price, R. W., primary, Epstein, L. G., additional, Becker, J. T., additional, Cinque, P., additional, Gisslen, M., additional, Pulliam, L., additional, and McArthur, J. C., additional
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- 2007
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32. Updated research nosology for HIV-associated neurocognitive disorders
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Antinori, A., primary, Arendt, G., additional, Becker, J. T., additional, Brew, B. J., additional, Byrd, D. A., additional, Cherner, M., additional, Clifford, D. B., additional, Cinque, P., additional, Epstein, L. G., additional, Goodkin, K., additional, Gisslen, M., additional, Grant, I., additional, Heaton, R. K., additional, Joseph, J., additional, Marder, K., additional, Marra, C. M., additional, McArthur, J. C., additional, Nunn, M., additional, Price, R. W., additional, Pulliam, L., additional, Robertson, K. R., additional, Sacktor, N., additional, Valcour, V., additional, and Wojna, V. E., additional
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- 2007
- Full Text
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33. Antiretroviral treatment reduces increased CSF neurofilament protein (NFL) in HIV-1 infection
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Mellgren, A, primary, Price, R. W., additional, Hagberg, L., additional, Rosengren, L., additional, Brew, B. J., additional, and Gisslen, M., additional
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- 2007
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34. Effects of antiretroviral treatment on blood-brain barrier integrity and intrathecal immunoglobulin production in neuroasymptomatic HIV-1-infected patients
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Abdulle, S, primary, Hagberg, L, additional, and Gisslen, M, additional
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- 2005
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35. The Effect on Human Immunodeficiency Virus Type 1 RNA Levels in Cerebrospinal Fluid after Initiation of Zidovudine or Didanosine
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Gisslen, M., primary, Norkrans, G., additional, Svennerholm, B., additional, and Hagberg, L., additional
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- 1997
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36. The urokinase receptor is overexpressed in the AIDS dementia complex and other neurological manifestations.
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Cinque P, Nebuloni M, Santovito ML, Price RW, Gisslen M, Hagberg L, Bestetti A, Vago G, Lazzarin A, Blasi F, and Sidenius N
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- 2004
37. Low cerebrospinal fluid b-amyloid 42 in patients with acute bacterial meningitis and normalization after treatment
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Sjogren, M., Gisslen, M., Vanmechelen, E., and Blennow, K.
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- 2001
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38. Intrathecal immune activation is associated with cerebrospinal fluid markers of neuronal destruction in AIDS patients
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Hagberg, L., Fuchs, D., Rosengren, L., and Gisslen, M.
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- 2000
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39. Increased cerebrospinal fluid protein tau concentration in neuro-AIDS
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Andersson, L.-M., Blennow, K., Fuchs, D., Svennerholm, B., and Gisslen, M.
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- 1999
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40. High levels in serum, but no signs of intrathecal synthesis of anti-sulfatide antibodies in HIV-1 infected individuals with or without central nervous system complications
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Gisslen, M., Lekman, A., and Fredman, P.
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- 1999
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41. Reduced baseline sensitivity to Maraviroc inhibition among R5 HIV-1 isolates from individuals with severe immunodeficiency
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Karlsson U, Repits J, Antonsson L, Cederfjäll E, Ljungberg B, Ålenius M, Alan Sabirsh, Gisslen M, Esbjörnsson J, and Jansson M
42. Highlights of the Global HIV-1 CSF Escape Consortium Meeting, 9 June 2016, Bethesda, MD, USA
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Joseph J, Cinque P, Colosi D, Dravid A, Ene L, Fox H, Gabuzda D, Gisslen M, Beth Joseph S, Letendre S, Ss, Mukerji, Nath A, Perez-Valero I, Persaud D, Rw, Price, Vr, Rao, Sacktor N, Swanstrom R, Winston A, and Valerie Wojna
43. Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1
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Bailey, J., Ajana, F., Arribas, J.R., Brunetta, J., Halota, W., Raffi, F., Brinson, C., Eron, J., Post, F., Ward, D., Katlama, C., Pineda, J.A., Rauch, A., Vandercam, B., Molina, J.-M., Slim, J., Crofoot, G., Prelutsky, D., Shamblaw, D., Van Wijngaerden, E., Opsomer, M., Pulido, F., Brown, K., Henn, S., Santos Gil, I., Perez-Valero, I., Flamholc, L., Ruane, P., Ricart, C., De Wit, S., Rey, D., Post, F.A., Murphy, D., Negredo, E., Gatell, J.M., Gathe, J., DeJesus, E., Iribarren, J.A., Rashbaum, B., Fehr, J., Dretler, R., Brar, I., Hagins, D., Voskuhl, G., Jain, M., Henry, W.K., Gasiorowski, J., Mills, A., Rivero, A., Van Landuyt, E., Gutierrez, F., Petrovic, R., Gazzard, B.G., Piekarska, A., Walmsley, S., de Vente, J., Girardy, P.-M., Shafran, S., Rachlis, A., Bhatti, L., Knobel, H., Sogorb, J.P., Cunningham, D., Mounzer, K., Klein, M., Galindo, M.J., Clarke, A., Stoeckle, M., Fichtenbaum, C., Dietz, C., EMERALD study group, Olivet, H., Poizot-Martin, I., Nahass, R., Richmond, G., Eron, J.J., Wilkin, A., Benson, P., Morales-Ramirez, J., Lathouwers, E., Lucasti, C., Moutschen, M., Osiyemi, O., Casado, J., Gallant, J., Jezorwski, J., Teicher, E., Cotte, L., Vandekerckhove, L., Podzamczer, D., Gisslen, M., Gutierrez, M.D.M., Bredeek, U.F., Waters, L., Scribner, A., Orkin, C., Conway, B., Yazdanpanah, Y., Felizarta, F., Reynes, J., Johnson, M.A., Ustianowski, A., Thalme, A., Martorell, C., McDonald, C., Tashima, K., Berenguer, J., Florence, E., Huhn, G., Shalit, P., Ramgopal, M., Witor, A., Blaxhult, A., Scarsella, A., Horban, A., and Hufkens, V.
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3. Good health - Abstract
Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF.
44. Highlights of the Global HIV-1 CSF Escape Consortium Meeting, 9 June 2016, Bethesda, MD, USA
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Joseph J, Cinque P, Colosi D, Dravid A, Ene L, Fox H, Dana Gabuzda, Gisslen M, Beth Joseph S, Letendre S, Ss, Mukerji, Nath A, Perez-Valero I, Persaud D, and Spudich S
45. Clinical Application of Cerebrospinal Fluid Neopterin Concentrations in HIV Infection
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Hagberg Lars, Andersson Lars-Magnus, Abdulle Sahra, and Gisslén Magnus
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neopterin ,cerebrospinal fluid ,hiv ,antiretroviral therapy ,Crystallography ,QD901-999 - Abstract
HIV-1 infects the central nervous system (CNS) and may cause AIDS dementia complex (ADC) and other neurologic complications. The cerebrospinal fluid (CSF) virus load is usually 0,5 -1 log lower than in blood, but in some patients the CSF quantitative HIV-1 RNA values exceed the paired blood samples. CSF neopterin concentrations are increased in all stages of HIV-1 infection, with the highest concentrations in AIDS patients and patients with CNS opportunistic infections. CD4 cell count and quantitative HIV RNA PCR tests in peripheral blood are used in clinical practice to monitor the HIV-1 infection and the anti-retroviral treatment effect. In most patients the anti-retroviral treatment response is similar in the cerebrospinal fluid (CSF) compare to the peripheral blood and the CSF viral load and neopterin concentrations are markedly reduced following treatment. ADC has become a rare complication. In spite of virological effective treatment many patients have a low grade intrathecal immunoactivation, measured as CSF neopterin concentrations above the 95% confidence interval found in IIIV-1 negative controls, after such a long time as after 2 years of anti-retroviral treatment.
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- 2004
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46. The definition of HIV-associated neurocognitive disorders: are we overestimating the real prevalence?
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Gisslén Magnus, Price Richard W, and Nilsson Staffan
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Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background A substantial prevalence of mild neurocognitive disorders has been reported in HIV, also in patients treated with combination antiretroviral therapy (cART). This includes a new disorder that has been termed asymptomatic neurocognitive impairment (ANI). Discussion ANI is identified by performance on formal neuropsychological testing that is at least 1 SD below the mean of normative scores in at least two cognitive domains out of at least five examined in patients without associated symptoms or evident functional impairment in daily living. While two tests are recommended to assess each domain, only one is required to fulfill this diagnostic criterion. Unfortunately, this definition necessitates that about 20% of the cognitively normal HIV-infected population is classified as suffering ANI. This liberal definition raises important ethical concerns and has as well diagnostic and therapeutic implications. Since neither its biological substrate, prognostic significance nor therapeutic implications are clearly established, we recommend that this diagnosis be modified or applied cautiously. Summary The diagnoses of less severe forms of neurocognitive disorders in HIV relies on the outcomes of neuropsychological testing, and a high proportion of HIV-infected patients with effective cART may be classified as neurocognitively abnormal using the current criteria. The definition of ANI is not stringent, and results in approximately 20% of the population being classified as abnormal. To us this seems an unacceptable false-positive rate.
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- 2011
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47. Lyme neuroborreliosis in HIV-1 positive men successfully treated with oral doxycycline: a case series and literature review
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Gisslén Magnus, Säll Christer, Bremell Daniel, and Hagberg Lars
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Medicine - Abstract
Abstract Introduction Lyme neuroborreliosis is the most common bacterial central nervous system infection in the temperate parts of the northern hemisphere. Even though human immunodeficiency virus (HIV) -1 infection is common in Lyme borreliosis endemic areas, only five cases of co-infection have previously been published. Four of these cases presented with typical Lyme neuroborreliosis symptoms such as meningoradiculitis and facial palsy, while a fifth case had more severe symptoms of encephalomyelitis. All five were treated with intravenous cephalosporins and clinical outcome was good for all but the fifth case Case presentations We present four patients with concomitant presence of HIV-1 infection and Lyme neuroborreliosis diagnosed in Western Sweden. Patient 1 was a 60-year-old Caucasian man with radicular pain and cognitive impairment. Patient 2 was a 39-year-old Caucasian man with headaches, leg weakness, and pontine infarction. Patient 3 was a 62-year-old Caucasian man with headaches, tremor, vertigo, and normal-pressure hydrocephalus. Patient 4 was a 50-year-old Caucasian man with radicular pain and peripheral facial palsy. Patients one, two, and three all had subnormal levels of CD4 cells, indicating impaired immunity. All patients were treated with oral doxycycline with good clinical outcome and normalization of CSF pleocytosis. Conclusion Given the low HIV-1 prevalence and medium incidence of Lyme neuroborreliosis in Western Sweden where these four cases were diagnosed, co-infection with HIV-1 and Borrelia is probably more common than previously thought. The three patients that were the most immunocompromised suffered from more severe and rather atypical neurological symptoms than are usually described among patients with Lyme neuroborreliosis. It is therefore important for doctors treating HIV patients to consider Lyme neuroborreliosis in a patient presenting with atypical neurological symptoms. All four patients were treated with oral doxycycline with a good outcome, further proving the efficacy of this regime.
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- 2011
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48. Rebound of residual plasma viremia after initial decrease following addition of intravenous immunoglobulin to effective antiretroviral treatment of HIV
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Sandberg Johan K, Sönnerborg Anders, Edén Arvid, Lindkvist Annica, Gonzalez Veronica D, Mellberg Tomas, Svennerholm Bo, and Gisslén Magnus
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract Background High dosage of intravenous immunoglobulin (IVIG) has been observed as a possible activator of HIV gene expression in latently infected resting CD4+ T-cells, leading to a substantial decrease in both the reservoir and the residual plasma viremia when added to effective ART. IVIG treatment has also been reported to expand T regulatory cells (Tregs). The aim of this study was to evaluate possible long-term effect of IVIG treatment on residual viremia and T-lymphocyte activation. Methods Nine HIV-infected subjects on effective ART included in a previously reported study on IVIG treatment were evaluated 48-104 weeks after therapy. In addition, 14 HIV-infected controls on suppressive ART were included. HIV-1 RNA was analyzed in cell-free plasma by using an ultrasensitive PCR-method with a detection limit of 2 copies/mL. T-lymphocyte activation markers and serum interleukins were measured. Results Plasma residual viremia rebounded to pre-treatment levels, 48-104 weeks after the initial decrease that was observed following treatment with high-dosage IVIG. No long-term effect was observed regarding T-lymphocyte activation markers, T-regulatory cells or serum interleukins. In a post-hoc analysis, a correlation between plasma HIV-1-RNA and CD4+ T-cell count was found in both IVIG-treated patients and controls. Conclusions These results indicate that the decrease in the latent HIV-1 pool observed during IVIG treatment is transient. Although not our primary objective, we found a correlation between HIV-1 RNA and CD4+ T-cell count suggesting the possibility that patients with a higher CD4+ T-cell count might harbor a larger residual pool of latently infected CD4+ T-cells.
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- 2011
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49. Cerebrospinal fluid neopterin: an informative biomarker of central nervous system immune activation in HIV-1 infection
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Bestetti Arabella, Spudich Serena, Brew Bruce J, Gisslen Magnus, Cinque Paola, Hagberg Lars, Price Richard W, and Fuchs Dietmar
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Abstract HIV-1 invades the central nervous system (CNS) in the context of acute infection, persists thereafter in the absence of treatment, and leads to chronic intrathecal immunoactivation that can be measured by the macrophage activation marker, neopterin, in cerebrospinal fluid (CSF). In this review we describe our experience with CSF neopterin measurements in 382 untreated HIV-infected patients across the spectrum of immunosuppression and HIV-related neurological diseases, in 73 untreated AIDS patients with opportunistic CNS infections, and in 233 treated patients. In untreated patients, CSF neopterin concentrations are almost always elevated and increase progressively as immunosuppression worsens and blood CD4 cell counts fall. However, patients with HIV dementia exhibit particularly high CSF neopterin concentrations, above those of patients without neurological disease, though patients with CNS opportunistic infections, including CMV encephalitis and cryptococcal meningitis, also exhibit high levels of CSF neopterin. Combination antiretroviral therapy, with its potent effect on CNS HIV infection and CSF HIV RNA, mitigates both intrathecal immunoactivation and lowers CSF neopterin. However, despite suppression of plasma and CSF HIV RNA to below the detection limits of clinical assays ( Although nonspecific, CSF neopterin can serve as a useful biomarker in the diagnosis of HIV dementia in the setting of confounding conditions, in monitoring the CNS inflammatory effects of antiretroviral treatment, and give valuable information to the cause of ongoing brain injury.
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- 2010
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50. Amyloid and tau cerebrospinal fluid biomarkers in HIV infection
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Rosengren Lars, Hagberg Lars, Spudich Serena, Brew Bruce J, Cinque Paola, Blennow Kaj, Andreasson Ulf, Krut Jan, Gisslén Magnus, Price Richard W, and Zetterberg Henrik
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Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. Methods In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPα and sAPPβ), amyloid beta fragment 1-42 (Aβ1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. Results CSF sAPPα and sAPPβ concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Aβ1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. Conclusions Parallel reductions of CSF sAPPα and sAPPβ in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.
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- 2009
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