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26 results on '"Pogliaghi M"'

6. Circulating microRNAs in Sera Correlate with Soluble Biomarkers of Immune Activation but Do Not Predict Mortality in ART Treated Individuals with HIV-1 Infection: A Case Control Study

Author

Murray, D. D., Suzuki, K., Law, M., Trebicka, J., Neuhaus, J., Wentworth, D., Johnson, M., Vjecha, M. J., Kelleher, A. D., Emery, S., Aagaard, B., Aragon, E., Arnaiz, J., Borup, L., Clotet, B., Dragsted, U., Fau, A., Gey, D., Grarup, J., Hengge, U., Herrero, P., Jansson, P., Jensen, B., Jensen, K., Juncher, H., Lopez, P., Lundgren, J. D., Matthews, C., Mollerup, D., Pearson, M., Phillips, A., Reilev, S., Tillmann, K., Varea, S., Angus, B., Babiker, A., Cordwell, B., Darbyshire, J., Dodds, W., Fleck, S., Horton, J., Hudson, F., Moraes, Y., Pacciarini, F., Palfreeman, A., Paton, N., Smith, N., Van Hooff, F., Bebchuk, J., Collins, G., Denning, E., Duchene, A., Fosdick, L., Harrison, M., Herman-Lamin, K., Krum, E., Larson, G., Neaton, J., Nelson, R., Quan, K., Quan, S., Schultz, T., Thompson, G., Wyman, N., Carey, C., Chan, F., Cooper, D., Courtney-Rodgers, D., Drummond, F., Harrod, M., Jacoby, S., Kearney, L., Lin, E., Pett, S., Robson, R., Seneviratne, N., Stewart, M., Watts, E., Finley, E., Gordin, F., Sanchez, A., Standridge, B., Belloso, W., Davey, R., Duprez, D., Gatell, J., Hoy, J., Lifson, A., Pederson, C., Perez, G., Price, R., Prineas, R., Rhame, F., Sampson, J., Worley, J., Modlin, J., Beral, V., Chaisson, R., Fleming, T., Hill, C., Kim, K., Murray, B., Pick, B., Seligmann, M., Weller, I., Cahill, K., Fox, L., Luzar, M., Martinez, A., Mcnay, L., Pierson, J., Tierney, J., Vogel, S., Costas, V., Eckstrand, J., Brown, S., Abusamra, L., Angel, E., Aquilia, S., Benetucci, J., Bittar, V., Bogdanowicz, E., Cahn, P., Casiro, A., Contarelli, J., Corral, J., Daciuk, L., David, D., Dobrzanski, W., Duran, A., Ebenrstejin, J., Ferrari, I., Fridman, D., Galache, V., Guaragna, G., Ivalo, S., Krolewiecki, A., Lanusse, I., Laplume, H., Lasala, M., Lattes, R., Lazovski, J., Lopardo, G., Losso, M., Lourtau, L., Lupo, S., Maranzana, A., Marson, C., Massera, L., Moscatello, G., Olivia, S., Otegui, I., Palacios, L., Parlante, A., Salomon, H., Sanchez, M., Somenzini, C., Suarez, C., Tocci, M., Toibaro, J., Zala, C., Agrawal, S., Ambrose, P., Anderson, C., Anderson, J., Baker, D., Beileiter, K., Blavius, K., Bloch, M., Boyle, M., Bradford, D., Britton, P., Brown, P., Busic, T., Cain, A., Carrall, L., Carson, S., Chenoweth, I., Chuah, J., Clark, F., Clemons, J., Clezy, K., Cortissos, P., Cunningham, N., Curry, M., Daly, L., D'Arcy-Evans, C., Del Rosario, R., Dinning, S., Dobson, P., Donohue, W., Doong, N., Downs, C., Edwards, E., Edwards, S., Egan, C., Ferguson, W., Finlayson, R., Forsdyke, C., Foy, L., Franic, T., Frater, A., French, M., Gleeson, D., Gold, J., Habel, P., Haig, K., Hardy, S., Holland, R., Hudson, J., Hutchison, R., Hyland, N., James, R., Johnston, C., Kelly, M., King, M., Kunkel, K., Lau, H., Leamy, J., Lester, D., Leung, J., Lohmeyer, A., Lowe, K., Macrae, K., Magness, C., Martinez, O., Maruszak, H., Medland, N., Miller, S., Murray, J., Negus, P., Newman, R., Ngieng, M., Nowlan, C., Oddy, J., Orford, N., Orth, D., Patching, J., Plummer, M., Price, S., Primrose, R., Prone, I., Ree, H., Remington, C., Richardson, R., Robinson, S., Rogers, G., Roney, J., Roth, N., Russell, D., Ryan, S., Sarangapany, J., Schmidt, T., Schneider, K., Shields, C., Silberberg, C., Shaw, D., Skett, J., Smith, D., Soo, T. M., Sowden, D., Street, A., Tee, B. K., Thomson, J., Topaz, S., Vale, R., Villella, C., Walker, A., Watson, A., Wendt, N., Williams, L., Youds, D., Aichelburg, A., Cichon, P., Gemeinhart, B., Rieger, A., Schmied, B., Touzeau-Romer, V., Vetter, N., Colebunders, R., Clumeck, N., Deroo, A., Kabeya, K., O'Doherty, E., De Wit, S., De Salles Amorim, C., Basso, C., Flint, S., Kallas, E., Levi, G., Lewi, D., Pereira, L., Da Silva, M., Souza, T., Toscano, A., Angel, J., Arsenault, M., Bast, M., Beckthold, B., Bouchard, P., Chabot, I., Clarke, R., Cohen, J., Cote, P., Ellis, M., Gagne, C., Gill, J., Houde, M., Johnston, B., Jubinville, N., Kato, C., Lamoureux, N., Latendre-Paquette, J., Lindemulder, A., Mcneil, A., Mcfarland, N., Montaner, J., Morrisseau, C., O'Neill, R., Page, G., Piche, A., Pongracz, B., Preziosi, H., Puri, L., Rachlis, A., Ralph, E., Raymond, I., Rouleau, D., Routy, J. P., Sandre, R., Seddon, T., Shafran, S., Sikora, C., Smaill, F., Stromberg, D., Trottier, S., Walmsley, S., Weiss, K., Williams, K., Zarowny, D., Baadegaard, B., Andersen, A. B., Boedker, K., Collins, P., Gerstoft, J., Jensen, L., Moller, H., Andersen, P. L., Loftheim, I., Mathiesen, L., Nielsen, H., Obel, N., Pedersen, C., Petersen, D., Jensen, L. P., Black, F. T., Aboulker, J. P., Aouba, A., Bensalem, M., Berthe, H., Blanc, C., Bornarel, D., Bouchaud, O., Boue, F., Bouvet, E., Brancon, C., Breaud, S., Brosseau, D., Brunet, A., Capitant, C., Ceppi, C., Chakvetadze, C., Cheneau, C., Chennebault, J. M., De Truchis, P., Delavalle, A. M., Delfraissy, J. F., Dellamonica, P., Dumont, C., Edeb, N., Fabre, G., Ferrando, S., Foltzer, A., Foubert, V., Gastaut, J. A., Gerbe, J., Girard, P. M., Goujard, C., Hoen, B., Honore, P., Hue, H., Hynh, T., Jung, C., Kahi, S., Katlama, C., Lang, J. M., Le Baut, V., Lefebvre, B., Leturque, N., Levy, Y., Loison, J., Maddi, G., Maignan, A., Majerholc, C., De Boever, C., Meynard, J. L., Michelet, C., Michon, C., Mole, M., Netzer, E., Pialoux, G., Poizot-Martin, I., Raffi, F., Ratajczak, M., Ravaux, I., Reynes, J., Salmon-Ceron, D., Sebire, M., Simon, A., Tegna, L., Tisne-Dessus, D., Tramoni, C., Viard, J. P., Vidal, M., Viet-Peaucelle, C., Weiss, L., Zeng, A., Zucman, D., Adam, A., Arasteh, K., Behrens, G., Bergmann, F., Bickel, M., Bittner, D., Bogner, J., Brockmeyer, N., Darrelmann, N., Deja, M., Doerler, M., Esser, S., Faetkenheuer, G., Fenske, S., Gajetzki, S., Goebel, F., Gorriahn, D., Harrer, E., Harrer, T., Hartl, H., Hartmann, M., Heesch, S., Jakob, W., Jager, H., Klinker, H., Kremer, G., Ludwig, C., Mantzsch, K., Mauss, S., Meurer, A., Niedermeier, A., Pittack, N., Plettenberg, A., Potthoff, A., Probst, M., Rittweger, M., Rockstroh, J., Ross, B., Rotty, J., Rund, E., Ruzicka, T., Schmidt, R., Schmutz, G., Schnaitmann, E., Schuster, D., Sehr, T., Spaeth, B., Staszewski, S., Stellbrink, H. J., Stephan, C., Stockey, T., Stoehr, A., Trein, A., Vaeth, T., Vogel, M., Wasmuth, J., Wengenroth, C., Winzer, R., Wolf, E., Mulcahy, F., Reidy, D., Cohen, Y., Drora, G., Eliezer, I., Godo, O., Kedem, E., Magen, E., Mamorsky, M., Pollack, S., Sthoeger, Z., Vered, H., Yust, I., Aiuti, F., Bechi, M., Bergamasco, A., Bertelli, D., Bruno, R., Butini, L., Cagliuso, M., Carosi, G., Casari, S., Chrysoula, V., Cologni, G., Conti, V., Costantini, A., Corpolongo, A., D'Offizi, G., Gaiottino, F., Di Pietro, M., Esposito, R., Filice, G., Francesco, M., Gianelli, E., Graziella, C., Magenta, L., Martellotta, F., Maserati, R., Mazzotta, F., Murdaca, G., Nardini, G., Nozza, S., Puppo, F., Pogliaghi, M., Ripamonti, D., Ronchetti, C., Rusconi, S., Rusconi, V., Sacchi, P., Silvia, N., Suter, F., Tambussi, G., Uglietti, A., Vechi, M., Vergani, B., Vichi, F., Vitiello, P., Iwamoto, A., Kikuchi, Y., Miyazaki, N., Mori, M., Nakamura, T., Odawara, T., Oka, S., Shirasaka, T., Tabata, M., Takano, M., Ueta, C., Watanabe, D., Yamamoto, Y., Erradey, I., Himmich, H., El Filali, K. M., Blok, W., Van Boxtel, R., Doevelaar, K. B. H., Van Eeden, A., Grijsen, M., Groot, M., Juttmann, J., Kuipers, M., Ligthart, S., Van Der Meulen, P., Lange, J., Langebeek, N., Reiss, P., Richter, C., Schoemaker, M., Schrijnders-Gudde, L., Septer-Bijleveld, E., Sprenger, H., Vermeulen, J., Ten Kate, R., Van De Ven, B., Bruun, J., Kvale, D., Maeland, A., Bakowska, E., Beniowski, M., Boron-Kaczmarska, A., Gasiorowski, J., Horban, A., Inglot, M., Knysz, B., Mularska, E., Parczewski, M., Pynka, M., Rymer, W., Szymczak, A., Aldir, M., Antunes, F., Baptista, C., Da Conceicao Vera, J., Doroana, M., Mansinho, K., Dos Santos, C. R. A., Valadas, E., Vaz Pinto, I., Chia, E., Foo, E., Karim, F., Lim, P. L., Panchalingam, A., Quek, A., Alcazar-Caballero, R., Arribas, J., Arrizabalaga, J., De Barron, X., Blanco, F., Bouza, E., Bravo, I., Calvo, S., Carbonero, L., Carpena, I., Castro, M., Cortes, L., Del Toro, M., Domingo, P., Elias, M., Espinosa, J., Estrada, V., Fernandez-Cruz, E., Fernandez, P., Freud, H., Fuster, M., Garcia, A., Garcia, G., Garrido, R., Gijon, P., Gonzalez-Garcia, J., Gil, I., Gonzalez, A., Gonzalez-Lahoz, J., Grosso, P. L., Gutierrez, M., Guzman, E., Iribarren, J., Jimenez, M., Jou, A., Juega, J., Lopez, J., Lozano, F., Martin-Carbonero, L., Mata, R., Mateo, G., Menasalvas, A., Mirelles, C., De Miguel Prieto, J., Montes, M., Moreno, A., Moreno, J., Moreno, V., Munoz, R., Ocampo, A., Ortega, E., Ortiz, L., Padilla, B., Parras, A., Paster, A., Pedreira, J., Pena, J., Perea, R., Portas, B., Puig, J., Pulido, F., Rebollar, M., De Rivera, J., Roca, V., Rodriguez-Arrondo, F., Rubio, R., Santos, J., Sanz, J., Sebastian, G., Segovia, M., Soriano, V., Tamargo, L., Viciana, P., Von Wichmann, M., Bratt, G., Hollander, A., Olov Pehrson, P., Petz, I., Sandstrom, E., Sonnerborg, A., Bernasconi, E., Gurtner, V., Ampunpong, U., Auchieng, C., Bowonwatanuwong, C., Chanchai, P., Chetchotisakd, P., Chuenyan, T., Duncombe, C., Horsakulthai, M., Kantipong, P., Laohajinda, K., Phanuphak, P., Pongsurachet, V., Pradapmook, S., Ruxruntham, K., Seekaew, S., Sonjai, A., Suwanagool, S., Techasathit, W., Ubolyam, S., Wankoon, J., Alexander, I., Dockrell, D., Easterbrook, P., Edwards, B., Evans, E., Fisher, M., Fox, R., Gazzard, B., Gilleran, G., Hand, J., Heald, L., Higgs, C., Jebakumar, S., Jendrulek, I., Johnson, S., Kinghorn, G., Kuldanek, K., Leen, C., Maw, R., Mckernan, S., Mclean, L., Morris, S., Murphy, M., O'Farrell, S., Ong, E., Peters, B., Stroud, C., Wansbrough-Jones, M., Weber, J., White, D., Williams, I., Wiselka, M., Yee, T., Adams, S., Allegra, D., Andrews, L., Aneja, B., Anstead, G., Arduino, R., Artz, R., Bailowitz, J., Banks, S., Baxter, J., Baum, J., Benator, D., Black, D., Boh, D., Bonam, T., Brito, M., Brockelman, J., Bruzzese, V., Burnside, A., Cafaro, V., Casey, K., Cason, L., Childress, G., Clark, C., Clifford, D., Climo, M., Cohn, D., Couey, P., Cuervo, H., Deeks, S., Dennis, M., Diaz-Linares, M., Dickerson, D., Diez, M., Di Puppo, J., Dodson, P., Dupre, D., Elion, R., Elliott, K., El-Sadr, W., Estes, M., Fabre, J., Farrough, M., Flamm, J., Follansbee, S., Foster, C., Frank, C., Franz, J., Frechette, G., Freidland, G., Frische, J., Fuentes, L., Funk, C., Geisler, C., Genther, K., Giles, M., Goetz, M., Gonzalez, M., Graeber, C., Graziano, F., Grice, D., Hahn, B., Hamilton, C., Hassler, S., Henson, A., Hopper, S., John, M., Johnson, L., Johnson, R., Jones, R., Kahn, J., Klimas, N., Kolber, M., Koletar, S., Labriola, A., Larsen, R., Lasseter, F., Lederman, M., Ling, T., Lusch, T., Macarthur, R., Machado, C., Makohon, L., Mandelke, J., Mannheimer, S., Markowitz, N., Martinez, M., Martinez, N., Mass, M., Masur, H., Mcgregor, D., Mcintyre, D., Mckee, J., Mcmullen, D., Mettinger, M., Middleton, S., Mieras, J., Mildvan, D., Miller, P., Miller, T., Mitchell, V., Mitsuyasu, R., Moanna, A., Mogridge, C., Moran, F., Murphy, R., Mushatt, D., Nahass, R., Nixon, D., O'Brien, S., Ojeda, J., Okhuysen, P., Olson, M., Osterberger, J., Owen, W., Pablovich, S., Patel, S., Pierone, G., Poblete, R., Potter, A., Preston, E., Rappoport, C., Regevik, N., Reyelt, M., Riney, L., Rodriguez-Barradas, M., Rodriguez, J., Roland, R., Rosmarin-DeStefano, C., Rossen, W., Rouff, J., Saag, M., Santiago, S., Sarria, J., Wirtz, S., Schmidt, U., Scott, C., Sheridan, A., Shin, A., Shrader, S., Simon, G., Slowinski, D., Smith, K., Spotkov, J., Sprague, C., States, D., Suh, C., Sullivan, J., Summers, K., Sweeton, B., Tan, V., Tanner, T., Tedaldi, E., Temesgen, Z., Thomas, D., Thompson, M., Tobin, C., Toro, N., Towner, W., Upton, K., Uy, J., Valenti, S., Van Der Horst, C., Vita, J., Voell, J., Walker, J., Walton, T., Wason, K., Watson, V., Wellons, A., Weise, J., White, M., Whitman, T., Williams, B., Williams, N., Windham, J., Witt, M., Workowski, K., Wortmann, G., Wright, T., Zelasky, C., Zwickl, B., Dietz, D., Chesson, C., Vjecha, M., Schmetter, B., Grue, L., Willoughby, M., Demers, A., Dragsted, U. B., Jensen, K. B., Jansson, P. O., Jensen, B. G., Benfield, T. L., Darbyshire, J. H., Babiker, G., Fleck, S. L., Collaco-Moraes, Y., Wyzydrag, L., Drummond, F. M., Connor, S. A., Satchell, C. S., Gunn, S., Delfino, M. A., Merlin, K., Mcginley, C., Neaton, J. D., Bartsch, G., George, M., Grund, B., Hogan, C., Miller, C., Roediger, M. P., Thackeray, L., Campbell, C., Lahart, C., Perlman, D., Rein, M., Dersimonian, R., Brody, B. A., Daar, E. S., Dubler, N. N., Fleming, T. R., Freeman, D. J., Kahn, J. P., Kim, K. M., Medoff, G., Modlin, J. F., Moellering, R., Murray, B. E., Robb, M. L., Scharfstein, D. O., Sugarman, J., Tsiatis, A., Tuazon, C., Zoloth, L., Klingman, K., Lehrman, S., Belloso, W. H., Losso, M. H., Benetucci, J. A., Bogdanowicz, E. P., Cahn, P. E., Casiro, A. D., Cassetti, I., Contarelli, J. M., Corral, J. A., Crinejo, A., David, D. O., Ishida, M. T., Laplume, H. E., Lasala, M. B., Lupo, S. H., Masciottra, F., Michaan, M., Ruggieri, L., Salazar, E., Hoy, J. F., Rogers, G. D., Allworth, A. M., Anderson, J. S. C., Armishaw, J., Barnes, K., Carr, A., Chiam, A., Chuah, J. C. P., Curry, M. C., Dever, R. L., Donohue, W. A., Doong, N. C., Dwyer, D. E., Dyer, J., Eu, B., Ferguson, V. W., French, M. A. H., Garsia, R. J., Hudson, J. H., Jeganathan, S., Konecny, P., Mccormack, C. L., Mcmurchie, M., Moore, R. J., Moussa, M. B., Piper, M., Read, T., Roney, J. J., Shaw, D. R., Silvers, J., Smith, D. J., Street, A. C., Vale, R. J., Wendt, N. A., Wood, H., Youds, D. W., Zillman, J., Tozeau, V., Dewit, S., De Roo, A., Leonard, P., Lynen, L., Moutschen, M., Pereira, L. C., Souza, T. N. L., Schechter, M., Zajdenverg, R., Almeida, M. M. T. B., Araujo, F., Bahia, F., Brites, C., Caseiro, M. M., Casseb, J., Etzel, A., Falco, G. G., Filho, E. C. J., Flint, S. R., Gonzales, R., Madruga, J. V. R., Passos, L. N., Reuter, T., Sidi, L. C., Toscano, A. L. C., Cherban, E., Conway, B., Dufour, C., Foster, A., Haase, D., Haldane, H., Klein, M., Lessard, B., Martel, A., Martel, C., Paradis, E., Schlech, W., Schmidt, S., Thompson, B., Vezina, S., Reyes, M. J. W., Northland, R., Ostergaard, L., Hergens, L., Loftheim, I. R., Raukas, M., Zilmer, K., Justinen, J., Ristola, M., Landman, R., Abel, S., Abgrall, S., Amat, K., Auperin, L., Barruet, R., Benalycherif, A., Benammar, N., Bentata, M., Besnier, J. M., Blanc, M., Cabie, A., Chavannet, P., Dargere, S., De La Tribonniere, X., Debord, T., Decaux, N., Delgado, J., Dupon, M., Durant, J., Frixon-Marin, V., Genet, C., Gerard, L., Gilquin, J., Jeantils, V., Kouadio, H., Leclercq, P., Lelievre, J. D., Michon, C. P., Nau, P., Pacanowski, J., Piketty, C., Salmon, D., Schmit, J. L., Serini, M. A., Tassi, S., Touam, F., Verdon, R., Weinbreck, P., Yazdanpanah, Y., Yeni, P., Fatkenheuer, G., Bitsch, S., Bogner, J. R., Goebel, F. D., Lehmann, C., Lennemann, T., Wasmuth, J. C., Wiedemeyer, K., Hatzakis, A., Touloumi, G., Antoniadou, A., Daikos, G. L., Dimitrakaki, A., Gargalianos-Kakolyris, P., Giannaris, M., Karafoulidou, A., Katsambas, A., Katsarou, O., Kontos, A. N., Kordossis, T., Lazanas, M. K., Panagopoulos, P., Panos, G., Paparizos, V., Papastamopoulos, V., Petrikkos, G., Sambatakou, H., Skoutelis, A., Tsogas, N., Xylomenos, G., Bergin, C. J., Mooka, B., Mamorksy, M. G., Agmon-Levin, N., Karplus, R., Maayan, S., Shahar, E., Turner, D., Abeli, C., Biglino, A., Bonora, S., De Gioanni, M., Di Perri, G., Montroni, M., Quirino, T., Raise, E., Honda, M., Ishisaka, M., Caplinskas, S., Uzdaviniene, V., Schmit, J. C., Staub, T., Mills, G. D., Blackmore, T., Masters, J. A., Morgan, J., Pithie, A., Brunn, J., Ormassen, V., La Rosa, A., Guerra, O., Espichan, M., Gutierrez, L., Mendo, F., Salazar, R., Knytz, B., Kwiatkowski, J., Castro, R. S., Horta, A., Miranda, A. C., Pinto, I. V., Vera, J., Rakhmanova, A., Vinogradova, E., Yakovlev, A., Zakharova, N., Wood, R., Orrel, C., Arnaiz, J. A., Carrillo, R., Dalmau, D., Jordano, Q., Knobel, H., Larrousse, M., Moreno, J. S., Oretaga, E., Pena, J. N., Hirschel, B., Spycher, R., Battegay, M., Bottone, S., Cavassini, M., Christen, A., Furrer, H. J., Gayet-Ageron, A., Genne, D., Hochstrasser, S., Moens, C., Muller, N., Nuesch, R., Ruxrungtham, K., Pumpradit, W., Dangthongdee, S., Kiertiburanakul, S., Klinbuayaem, V., Mootsikapun, P., Nonenoy, S., Piyavong, B., Prasithsirikul, W., Raksakulkarn, P., Gazzard, B. G., Ainsworth, J. G., Angus, B. J., Barber, T. J., Brook, M. G., Care, C. D., Chadwick, D. R., Chikohora, M., Churchill, D. R., Cornforth, D., Dockrell, D. H., Easterbrook, P. J., Fox, P. A., Gomez, P. A., Gompels, M. M., Harris, G. M., Herman, S., Jackson, A. G. A., Jebakumar, S. P. R., Kinghorn, G. R., Kuldanek, K. A., Larbalestier, N., Lumsden, M., Maher, T., Mantell, J., Muromba, L., Orkin, C. M., Peters, S., Peto, T. E. A., Portsmouth, S. D., Rajamanoharan, S., Ronan, Schwenk, A., Slinn, M. A., Stroud, C. J., Thomas, R. C., Wansbrough-Jones, M. H., Whiles, H. J., White, D. J., Williams, E., Williams, G., Youle, M., Abrams, D. I., Acosta, E. A., Adamski, A., Antoniskis, D., Aragon, D. R., Barnett, B. J., Baroni, C., Barron, M., Baxter, J. D., Beers, D., Beilke, M., Bemenderfer, Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Crane, L. R., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, A., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. J., Farthing, C. F., Ferrell-Gonzalez, P., Flynn, H., Frank, M., Freeman, K. F., French, N., Friedland, G., Fujita, N., Gahagan, L., Gilson, I., Goetz, M. B., Goodwin, E., Guity, C. K., Gulick, P., Gunderson, E. R., Hale, C. M., Hannah, K., Henderson, H., Hennessey, K., Henry, W. K., Higgins, T., Hodder, S. L., Horowitz, H. W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Luskin-Hawk, R., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. W., Ravishankar, J., Reeder, J., Reilly, N. A., Reyelt, C., Riddell, J., Rimland, D., Robinson, M. L., Rodriguez, A. E., Rodriguez Derouen, V., Rosmarin, C., Rossen, W. L., Rouff, J. R., Sands, M., Savini, C., Schrader, S., Schulte, M. M., Scott, R., Seedhom, H., Sension, M., Sheblehall, A., Shuter, J., Slater, L. N., Slotten, R., Smith, M., Snap, S., States, D. M., Stringer, G., Summers, K. K., Swanson, K., Sweeton, I. B., Szabo, S., Tedaldi, E. M., Telzak, E. E., Thompson, M. A., Thompson, S., Bong, C. T. H., Vaccaro, A., Vasco, L. M., Vecino, I., Verlinghieri, G. K., Visnegarwala, F., Wade, H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., and Pacheco, Antonio Guilherme

Subjects
Adult, CD4-Positive T-Lymphocytes, Male, General Science & Technology, Anti-HIV Agents, T cell, lcsh:Medicine, Antiretroviral Therapy, HIV Infections, Biology, Essential hypertension, Logistic regression, Malignancy, Acquired immunodeficiency syndrome (AIDS), Clinical Research, Antiretroviral Therapy, Highly Active, microRNA, medicine, Genetics, 2.1 Biological and endogenous factors, Humans, Highly Active, Aetiology, lcsh:Science, Genetic Association Studies, Multidisciplinary, lcsh:R, Case-control study, Middle Aged, medicine.disease, 3. Good health, Circulating MicroRNA, MicroRNAs, medicine.anatomical_structure, Infectious Diseases, Good Health and Well Being, INSIGHT ESPRIT and SMART Study Groups, Immunology, HIV-1, HIV/AIDS, lcsh:Q, Female, Infection, Biomarkers, Biotechnology, Research Article
Abstract

Introduction The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR-145 correlated with nadir CD4+ T cell count. Discussion No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection.

Published
2015

7. Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study

Author

Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, Lundgren, J. D., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Franquet, X., Sabin, C. A., Phillips, A., Kirk, O., Reiss, P., Weber, R., Pradier, C., Law, M., d'Arminio Monforte, A., Dabis, F., El-Sadr, W. M., De Wit, S., Ryom, L., Kamara, D., Smith, C., Mocroft, A., Tverland, J., Mansfeld, M., Nielsen, J., Raben, D., Salbøl Brandt, R., Rickenbach, M., Fanti, I., Krum, E., Hillebregt, M., Geffard, S., Sundström, A., Delforge, M., Fontas, E., Torres, F., Mcmanus, H., Wright, S., Kjær, J., Sjøl, A., Meidahl, P., Helweg-Larsen, J., Schmidt Iversen, J., Ross, M., Fux, C. A., Morlat, P., Moranne, O., Kesselring, A. M., Kamara, D. A., Friis-Møller, N., Kowalska, J., Sabin, C., Bruyand, M., Bower, M., Fätkenheuer, G., Donald, A., Grulich, A., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T. M., Wit, F. W. M. N., Godfried, M. H., van der Poll, T., Nellen, F. J. B., Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., van der Valk, M., Goorhuis, A., Hovius, J. W., van Eden, J., Henderiks, A., van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Westerman, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., Korsten-Vorstermans, E. M. H. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van der Plas, A., Weijsenfeld, A. M., van der Ende, M. E., de Vries-Sluijs, T. E. M. S., C. M. van Gorp, E., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Hassing, R. J., van der Feltz, M., Bassant, N., van Beek, J. E. A., Vriesde, M., van Zonneveld, L. M., de Oude-Lubbers, A., van den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., de Zeeuw- de Man, M., Broekhoven-Kruijne, M. J., Schutten, M., Osterhaus, A. D. M. E., Boucher, C. A. B., Driessen, G. J. A., van Rossum, A. M. C., van der Knaap, L. C., Visser, E., Branger, J., H. M. Duijf-van de Ven, C. J., Schippers, E. F., van Nieuwkoop, C., Brimicombe, R. W., van IJperen, J. M., van der Hut, G., Franck, P. F. H., van Eeden, A., Brokking, W., Groot, M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., van den Berg, J. F., van Hulzen, A. G. W., van der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., Schoemaker, M., Bermon, N., van der Reijden, W. A., Jansen, R., Herpers, B. L., Veenendaal, D., Kroon, F. P., Arend, S. M., de Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Moons, C., Claas, E. C. J., Kroes, A. C. M., den Hollander, J. G., Pogany, K., Kastelijns, M., Smit, J. V., Smit, E., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg Maes, B., Savelkoul, P. H. M., Loo, I. H., Weijer, S., El Moussaoui, R., Heitmuller, M., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., Pronk, D., van Truijen-Oud, F. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., van Vonderen, M. G. A., van Houte, D. P. F., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-van de Plas, M., Heins, H., Lucas, E., Brinkman, K., Frissen, P. H. J., Blok, W. L., Schouten, W. E. M., Bosma, A. S., Brouwer, C. J., Geerders, G. 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J., Gayet-Ageron, A., Genné, D., Hochstrasser, S., Moens, C., Nüesch, R., Ruxrungtham, K., Pumpradit, W., Dangthongdee, S., Kiertiburanakul, S., Klinbuayaem, V., Mootsikapun, P., Nonenoy, S., Piyavong, B., Prasithsirikul, W., Raksakulkarn, P., Gazzard, B. G., Ainsworth, J. G., Angus, B. J., Barber, T. J., Brook, M. G., Care, C. D., Chadwick, D. R., Chikohora, M., Churchill, D. R., Cornforth, D., Dockrell, D. H., Easterbrook, P. J., Fox, P. A., Gomez, P. A., Gompels, M. M., Harris, G. M., Herman, S., Jackson, A. G. A., Jebakumar, S. P. R., Kinghorn, G. R., Kuldanek, K. A., Larbalestier, N., Lumsden, M., Maher, T., Mantell, J., Muromba, L., Orkin, C. M., Peters, B. S., Peto, T. E. A., Portsmouth, S. D., Rajamanoharan, S., Ronan, A., Schwenk, A., Slinn, M. A., Stroud, C. J., Thomas, R. C., Wansbrough-Jones, M. H., Whiles, H. J., White, D. J., Williams, E., Williams, I. G., Acosta, E. A., Adamski, A., Antoniskis, D., Aragon, D. R., Barnett, B. J., Baroni, C., Barron, M., Baxter, J. D., Beers, D., Beilke, M., Bemenderfer, D., Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, D. E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Clark, C., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, E., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. J., Farthing, C. F., Ferrell-Gonzalez, P., Flynn, H., Frank, M., Freeman, K. F., French, N., Fujita, N., Gahagan, L., Gilson, I., Goetz, M. B., Goodwin, E., Guity, C. K., Gulick, P., Gunderson, E. R., Hale, C. M., Hannah, K., Henderson, H., Hennessey, K., Henry, W. K., Higgins, D. T., Hodder, S. L., Horowitz, H. W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. W., Ravishankar, J., Reeder, J., Reilly, N. A., Reyelt, C., Riddell, J., Rimland, D., Robinson, M. L., Rodriguez, A. E., Rodriguez-Barradas, M. C., Rodriguez Derouen, V., Rosmarin, C., Rossen, W. L., Rouff, J. R., Sampson, J. H., Sands, M., Savini, C., Schrader, S., Schulte, M. M., Scott, R., Seedhom, H., Sension, M., Sheble-Hall, A., Shuter, J., Slater, L. N., Slotten, R., Smith, M., Snap, S., States, D. M., Stringer, G., Summers, K. K., Swanson, K., Sweeton, I. B., Szabo, S., Tedaldi, E. M., Telzak, E. E., Thompson, M. A., Thompson, S., Ting Hong Bong, C., Vaccaro, A., Vasco, L. M., Vecino, I., Verlinghieri, G. K., Visnegarwala, F., Wade, B. H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, A. M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., University College of London [London] (UCL), University of Copenhagen = Københavns Universitet (KU), University of New South Wales [Sydney] (UNSW), University of Amsterdam [Amsterdam] (UvA), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Med Microbiol, Infect Dis & Infect Prev, RS: NUTRIM - R3 - Chronic inflammatory disease and wasting, RS: CAPHRI School for Public Health and Primary Care, RS: CAPHRI - R4 - Health Inequities and Societal Participation, Interne Geneeskunde, Chemical Biology, Mocroft, A, Lundgren, J, Ross, M, Law, M, Reiss, P, Kirk, O, Smith, C, Wentworth, D, Neuhaus, J, Fux, C, Moranne, O, Morlat, P, Johnson, M, Ryom, L, Gori, A, Internal medicine, CCA - Innovative therapy, ICaR - Circulation and metabolism, Medical Microbiology and Infection Prevention, CCA - Disease profiling, CCA - Immuno-pathogenesis, Plastic, Reconstructive and Hand Surgery, Mocroft, Amanda, Lundgren, Jens D., Ross, Michael, Law, Matthew, Reiss, Peter, Kirk, Ole, Smith, Colette, Wentworth, Deborah, Neuhaus, Jacqueline, Fux, Christoph A., Moranne, Olivier, Morlat, Phillipe, Johnson, Margaret A., Ryom, Lene, D:a:d Study, Group, Castagna, Antonella, the Royal Free Hospital Clinic, Cohort, and the, Insight, Smart, and ESPRIT, Study, Clinicum, Department of Medicine, Herrada, Anthony, University of Copenhagen = Københavns Universitet (UCPH), AII - Amsterdam institute for Infection and Immunity, APH - Amsterdam Public Health, Global Health, Other departments, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, General Internal Medicine, Center of Experimental and Molecular Medicine, Graduate School, Gastroenterology and Hepatology, Dermatology, ACS - Amsterdam Cardiovascular Sciences, Other Research, Anesthesiology, and Bartlett, John

Subjects
Male, Adult, Age Factors, Anti-HIV Agents, CD4 Lymphocyte Count, Clinical Decision-Making, Comorbidity, Female, HIV, HIV Infections, HIV Seropositivity, Humans, Incidence, Kidney, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic, Risk, Risk Assessment, Sex Factors, urologic and male genital diseases, Biochemistry, 0302 clinical medicine, ANTIRETROVIRAL THERAPY, Adult, Age Factors, Anti-HIV Agents, CD4 Lymphocyte Count, Clinical Decision-Making, Comorbidity, Female, HIV, HIV Infections, HIV Seropositivity, Humans, Incidence, Kidney, Male, Middle Aged, Prospective Studies, Renal Insufficiency, Chronic, Risk, Risk Assessment, Sex Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Age Factor, Chronic, STAGE RENAL-DISEASE, PROTEINURIA, virus diseases, 11 Medical And Health Sciences, General Medicine, ASSOCIATION, 6. Clean water, female genital diseases and pregnancy complications, 3. Good health, HIV/AIDS, Medicine, Infection, psychological phenomena and processes, Human, medicine.medical_specialty, Renal function, NEFROPATIAS, chronic kidney disease, risk score model, 12. Responsible consumption, ESPRIT study group, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Clinical Research, D:A:D study group, Intensive care medicine, medicine (all), Molecular Biology, Royal Free Hospital Clinic Cohort, Prevention, Anti-HIV Agent, medicine.disease, Prospective Studie, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Immunology, Kidney Disease, PREDICTION, POSITIVE PERSONS, 030232 urology & nephrology, Sex Factor, SDG 3 – Goede gezondheid en welzijn, Medical and Health Sciences, GLOMERULAR-FILTRATION-RATE, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, INSIGHT study group, HIV Infection, LIFE EXPECTANCY, 030212 general & internal medicine, Renal Insufficiency, Prospective cohort study, Framingham Risk Score, Incidence (epidemiology), adult, age factors, anti-hiv agents, CD4 lymphocyte count, clinical decision-making, comorbidity, female, hiv, hiv infections, hiv seropositivity, humans, incidence, kidney, male, middle aged, prospective studies, renal insufficiency, chronic, risk, risk assessment, sex factors, SMART study group, 6.1 Pharmaceuticals, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Patient Safety, Risk assessment, Biotechnology, Research Article, Settore MED/17 - MALATTIE INFETTIVE, NO, A:D study group [D], General & Internal Medicine, Diabetes mellitus, mental disorders, medicine, EXPOSURE, business.industry, Evaluation of treatments and therapeutic interventions, Cell Biology, [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, INDIVIDUALS, Good Health and Well Being, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Kidney disease
Abstract

Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166–3,367); NNTH was 202 (95% CI 159–278) and 21 (95% CI 19–23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506–1462), 88 (95% CI 69–121), and 9 (95% CI 8–10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3–12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6–8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD., Editors’ Summary Background About 35 million people are currently infected with HIV, the virus that causes AIDS. HIV destroys CD4 lymphocytes and other immune system cells, leaving infected individuals susceptible to other infections. HIV infection can be controlled, but not cured, using combination antiretroviral therapy (cART), and, nowadays, the life expectancy of many HIV-positive individuals is similar to that of HIV-negative people. HIV-positive individuals nevertheless experience some illnesses more frequently than HIV-negative people do. For example, up to a third of HIV-positive individuals develop chronic kidney disease (CKD), which is associated with an increased risk of cardiovascular disease and death. Persons with CKD may have an impaired effect of the filtration units in the kidneys that remove waste products and excess water from the blood to make urine, thereby leading to a reduced blood filtration rate (the estimated glomerular filtration rate [eGFR]) and waste product accumulation in the blood. Symptoms of CKD, which rarely occur until the disease is advanced, include tiredness, swollen feet, and frequent urination. Advanced stages of CKD cannot be cured, but its progression can be slowed by, for example, controlling hypertension (high blood pressure) and diabetes (two CDK risk factors) and by adopting a healthy lifestyle. Why Was This Study Done? The burden of CKD may increase among HIV-positive individuals as they age, and clinicians need to know which individuals are at high risk of developing CKD when choosing cART regimens for their patients. In addition, clinicians need to be able to identify those HIV-positive individuals at greatest risk of CKD so that they can monitor them for early signs of kidney disease. Some antiretroviral drugs—for example, tenofovir and atazanavir/ritonavir (a boosted protease inhibitor)—are associated with kidney damage. Clinicians may need to weigh the benefits and risks of giving such potentially nephrotoxic drugs to individuals who already have a high CKD risk. Here, the researchers develop and validate a simple, widely applicable risk score (a risk prediction model) for CKD among HIV-positive individuals and investigate the relationship between CKD and potentially nephrotoxic antiretroviral drugs among individuals with different CKD risk score profiles. What Did the Researchers Do and Find? To develop their CKD risk score, the researchers used clinical and demographic data collected from 17,954 HIV-positive individuals enrolled in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study who had an eGFR > 60 ml/min/1.73 m2 and were not taking a potentially nephrotoxic antiretroviral at baseline. During 103,185 person-years of follow-up, 641 individuals developed CKD. Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease predicted CKD. The researchers included these nine factors in their risk score model (which is available online) and defined three risk groups: low (risk score < 0), medium (risk score 0–4), and high (risk score ≥ 5) risk of CKD development in the next five years. Specifically, there was a 1 in 393, 1 in 47, and 1 in 6 chance of developing CKD in the next five years in the low, medium, and high risk groups, respectively. Because some patients started to use potentially nephrotoxic antiretroviral drugs during follow-up, the researchers were able to use their risk score model to calculate how many patients would have to be treated with one of these drugs for an additional patient to develop CKD over five years in each risk group. This “number needed to harm” (NNTH) for patients starting treatment with tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor was 739, 88, and 9 in the low, medium, and high risk groups, respectively. Finally, the researchers validated the accuracy of their risk score in two independent HIV study groups. What Do These Findings Mean? These findings provide a simple, validated risk score for CKD and indicate that the NNTH when starting potentially nephrotoxic antiretrovirals was low among HIV-positive individuals at the highest risk of CKD (i.e., treating just nine individuals with nephrotoxic antiretroviral drugs will likely lead to an additional case of CKD in five years). Although various aspects of the study, including the lack of data on race, limit the accuracy of these findings, these findings highlight the need for monitoring, screening, and chronic disease prevention to minimize the risk of HIV-positive individuals developing diabetes, hypertension, or cardiovascular disease, or becoming coinfected with hepatitis C, all of which contribute to the CKD risk score. Moreover, the development of a tool for estimating an individual’s five-year risk of developing CKD with or without the addition of potentially nephrotoxic antiretroviral drugs will enable clinicians and patients to weigh the benefits of certain antiretroviral drugs against the risk of CKD and make informed decisions about treatment options. Additional Information Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001809. Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and personal stories about living with AIDS/HIV Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including personal stories about living with HIV/AIDS The World Health Organization provides information on all aspects of HIV/AIDS (in several languages), including its guidelines on the use of ART for treating and preventing HIV infection The UNAIDS World AIDS Day Report 2014 provides up-to-date information about the AIDS epidemic and efforts to halt it The UK National Health Service Choices website provides information for patients on chronic kidney disease, including some personal stories The US National Kidney Foundation, a not-for-profit organization, provides information about chronic kidney disease (in English and Spanish) A tool for calculating the CDK risk score developed in this study is available Additional information about the D:A:D study is available, Amanda Mocroft and colleagues develop and validate a model for determining risk of developing chronic kidney disease for individuals with HIV if treated with different antiretroviral therapies.

Published
2015

9. Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Author

Mocroft, A., Lundgren, J. D., Ross, M., Law, M., Reiss, P., Kirk, O., Smith, C., Wentworth, D., Neuhaus, J., Fux, C. A., Moranne, O., Morlat, P., Johnson, M. A., Ryom, L., Powderly, B., Shortman, N., Moecklinghoff, C., Reilly, G., Franquet, X., Sabin, C. A., Phillips, A., Weber, R., Pradier, C., d'Arminio Monforte, A., Dabis, F., El-Sadr, W. M., De Wit, S., Kamara, D., Tverland, J., Mansfeld, M., Nielsen, J., Raben, D., Salbol Brandt, R., Rickenbach, M., Fanti, I., Krum, E., Hillebregt, M., Geffard, S., Sundstrom, A., Delforge, M., Fontas, E., Torres, F., Mcmanus, H., Wright, S., Kjaer, J., Sjol, A., Meidahl, P., Helweg-Larsen, J., Schmidt Iversen, J., Kesselring, A. M., Friis-Moller, N., Kowalska, J., Sabin, C., Bruyand, M., Kamara, D. A., Bower, M., Fatkenheuer, G., Donald, A., Grulich, A., Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T. M., Wit, F. W. M. N., Godfried, M. H., van der Poll, T., Nellen, F. J. B., Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., Wiersinga, W. J., van der Valk, M., Goorhuis, A., Hovius, J. W., van Eden, J., Henderiks, A., van Hes, A. M. H., Mutschelknauss, M., Nobel, H. E., Pijnappel, F. J. J., Westerman, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Thomas, X. V., van den Berge, M., Stegeman, A., Baas, S., Hage de Looff, L., Versteeg, D., Pronk, M. J. H., Ammerlaan, H. S. M., Korsten-Vorstermans, E. M. H. M., de Munnik, E. S., Jansz, A. R., Tjhie, J., Wegdam, M. C. A., Deiman, B., Scharnhorst, V., van der Plas, A., Weijsenfeld, A. M., van der Ende, M. E., de Vries-Sluijs, T. E. M. S., C. M. van Gorp, E., Schurink, C. A. M., Nouwen, J. L., Verbon, A., Rijnders, B. J. A., Bax, H. I., Hassing, R. J., van der Feltz, M., Bassant, N., van Beek, J. E. A., Vriesde, M., van Zonneveld, L. M., de Oude-Lubbers, A., van den Berg-Cameron, H. J., Bruinsma-Broekman, F. B., de Groot, J., de Zeeuw- de Man, M., Broekhoven-Kruijne, M. J., Schutten, M., Osterhaus, A. D. M. E., Boucher, C. A. B., Driessen, G. J. A., van Rossum, A. M. C., van der Knaap, L. C., Visser, E., Branger, J., H. M. Duijf-van de Ven C., J., Schippers, E. F., van Nieuwkoop, C., Brimicombe, R. W., van IJperen, J. M., van der Hut, G., Franck, P. F. H., van Eeden, A., Brokking, W., Groot, M., Damen, M., Kwa, I. S., Groeneveld, P. H. P., Bouwhuis, J. W., van den Berg, J. F., van Hulzen, A. G. W., van der Bliek, G. L., Bor, P. C. J., Bloembergen, P., Wolfhagen, M. J. H. M., Ruijs, G. J. H. M., van Lelyveld, S. F. L., Soetekouw, R., Hulshoff, N., van der Prijt, L. M. M., Schoemaker, M., Bermon, N., van der Reijden, W. A., Jansen, R., Herpers, B. L., Veenendaal, D., Kroon, F. P., Arend, S. M., de Boer, M. G. J., Bauer, M. P., Jolink, H., Vollaard, A. M., Dorama, W., Moons, C., Claas, E. C. J., Kroes, A. C. M., den Hollander, J. G., Pogany, K., Kastelijns, M., Smit, J. V., Smit, E., Bezemer, M., van Niekerk, T., Pontesilli, O., Lowe, S. H., Oude Lashof, A., Posthouwer, D., Ackens, R. P., Schippers, J., Vergoossen, R., Weijenberg Maes, B., Savelkoul, P. H. M., Loo, I. H., Weijer, S., El Moussaoui, R., Heitmuller, M., Kortmann, W., van Twillert, G., Cohen Stuart, J. W. T., Diederen, B. M. W., Pronk, D., van Truijen-Oud, F. A., Leyten, E. M. S., Gelinck, L. B. S., van Hartingsveld, A., Meerkerk, C., Wildenbeest, G. S., Mutsaers, J. A. E. M., Jansen, C. L., van Vonderen, M. G. A., van Houte, D. P. F., Dijkstra, K., Faber, S., Weel, J., Kootstra, G. J., Delsing, C. E., van der Burg-van de Plas, M., Heins, H., Lucas, E., Brinkman, K., Frissen, P. H. J., Blok, W. L., Schouten, W. E. M., Bosma, A. S., Brouwer, C. J., Geerders, G. F., Hoeksema, K., Kleene, M. J., van der Meche, I. B., Toonen, A. J. M., Wijnands, S., van Ogtrop, M. L., Koopmans, P. P., Keuter, M., van der Ven, A. J. A. M., ter Hofstede, H. J. M., Dofferhoff, A. S. M., van Crevel, R., Albers, M., Bosch, M. E. W., Grintjes-Huisman, K. J. T., Zomer, B. J., Stelma, F. F., Burger, D., Richter, C., van der Berg, J. P., Gisolf, E. H., ter Beest, G., van Bentum, P. H. M., Langebeek, N., Tiemessen, R., Swanink, C. M. A., Veenstra, J., Lettinga, K. D., Spelbrink, M., Sulman, H., Witte, E., Peerbooms, P. G. H., Mulder, J. W., Vrouenraets, S. M. E., Lauw, F. N., van Broekhuizen, M. C., Paap, H., Vlasblom, D. J., Oudmaijer Sanders, E., Smits, P. H. M., Rosingh, A. W., Verhagen, D. W. M., Geilings, J., van Kasteren, M. E. E., Brouwer, A. E., de Kruijf-van de Wiel, B. A. F. M., Kuipers, M., Santegoets, R. M. W. J., van der Ven, B., Marcelis, J. H., G. M. Buiting, A., Kabel, P. J., Bierman, W. F. W., Sprenger, H. G., Scholvinck, E. H., van Assen, S., Wilting, K. R., Stienstra, Y., de Groot-de Jonge, H., van der Meulen, P. A., de Weerd, D. A., Niesters, H. G. M., Riezebos-Brilman, A., van Leer-Buter, C. C., Hoepelman, A. I. M., Schneider, M. M. 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L., Cohen, Y., Drora, G., Eliezer, I., Godo, O., Kedem, E., Magen, E., Mamorsky, M., Sthoeger, Z., Vered, H., Aiuti, F., Bechi, M., Bergamasco, A., Bertelli, D., Bruno, R., Butini, L., Cagliuso, M., Carosi, G., Casari, S., Chrysoula, V., Cologni, G., Conti, V., Corpolongo, A., D'Offizi, G., Gaiottino, F., Di Pietro, M., Filice, G., Francesco, M., Gianelli, E., Graziella, C., Magenta, L., Martellotta, F., Maserati, R., Murdaca, G., Nardini, G., Nozza, S., Puppo, F., Pogliaghi, M., Ripamonti, D., Ronchetti, C., Rusconi, V., Sacchi, P., Silvia, N., Suter, F., Tambussi, G., Uglietti, A., Vechi, M., Vergani, B., Vichi, F., Vitiello, P., Iwamoto, A., Kikuchi, Y., Miyazaki, N., Mori, M., Nakamura, T., Odawara, T., Oka, S., Shirasaka, T., Tabata, M., Takano, M., Ueta, C., Watanabe, D., Yamamoto, Y., Erradey, I., Himmich, H., Marhoum El Filali, K., Blok, W., van Boxtel, R., Brinkman H Doevelaar, K., Grijsen, M., Juttmann, J., Ligthart, S., van der Meulen, P., Lange, J., Schrijnders-Gudde, L., Septer-Bijleveld, E., Sprenger, H., Vermeulen, J., ten Kate, R., van de Ven, B., Kvale, D., Inglot, M., Rymer, W., Szymczak, A., Aldir, M., Baptista, C., da Conceicao Vera, J., Raquel A dos Santos, C., Valadas, E., Vaz Pinto, I., Chia, E., Foo, E., Karim, F., Lim, P. 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L., Clifford, D., Climo, M., Couey, P., Cuervo, H., Deeks, S., Dennis, M., Diaz-Linares, M., Dickerson, D., Diez, M., Di Puppo, J., Dodson, P., Dupre, D., Elion, R., Elliott, K., El-Sadr, W., Estes, M., Fabre, J., Farrough, M., Flamm, J., Follansbee, S., Foster, C., Frank, C., Franz, J., Frechette, G., Freidland, G., Frische, J., Fuentes, L., Funk, C., Geisler, C., Genther, K., Giles, M., Goetz, M., Gonzalez, M., Graeber, C., Graziano, F., Grice, D., Hahn, B., Hamilton, C., Hassler, S., Henson, A., Hopper, S., John, M., Johnson, L., Johnson, R., Jones, R., Kahn, J., Klimas, N., Kolber, M., Koletar, S., Labriola, A., Larsen, R., Lasseter, F., Lederman, M., Ling, T., Lusch, T., Macarthur, R., Machado, C., Makohon, L., Mandelke, J., Mannheimer, S., Martinez, M., Martinez, N., Mass, M., Masur, H., Mcgregor, D., Mcintyre, D., Mckee, J., Mcmullen, D., Mettinger, M., Middleton, S., Mieras, J., Mildvan, D., Miller, P., Miller, T., Mitchell, V., Mitsuyasu, R., Moanna, A., Mogridge, C., Moran, F., Murphy, R., Nahass, R., Nixon, D., O'Brien, S., Ojeda, J., Okhuysen, P., Olson, M., Osterberger, J., Owen, W., Pablovich, S. S., Patel, S., Pierone, G., Poblete, R., Potter, A., Preston, E., Rappoport, C., Regevik, N., Reyelt, M., Riney, L., Rodriguez-Barradas, M., Rodriguez, M., Rodriguez, J., Roland, R., Rosmarin-DeStefano, C., Rossen, W., Rouff, J., Saag, M., Santiago, S., Sarria, J., Wirtz, S., Schmidt, U., Scott, C., Sheridan, A., Shin, A., Shrader, S., Slowinski, D., Smith, K., Spotkov, J., Sprague, C., States, D., Suh, C., Sullivan, J., Summers, K., Sweeton, B., Tan, V., Tanner, T., Temesgen, Z., Thomas, D., Thompson, M., Tobin, C., Toro, N., Towner, W., Upton, K., Uy, J., Valenti, S., van der Horst, C., Vita, J., Voell, J., Walker, J., Walton, T., Wason, K., Watson, V., Wellons, A., Weise, J., White, M., Whitman, T., Williams, B., Williams, N., Windham, J., Witt, M., Workowski, K., Wortmann, G., Wright, T., Zelasky, C., Zwickl, B., Finley, E., Dietz, D., Chesson, C., Vjecha, M., Schmetter, B., Grue, L., Willoughby, M., Demers, A., Dragsted, U. B., Jensen, K. B., Jansson, P. O., Jensen, B. G., Benfield, T. L., Darbyshire, J. H., Babiker, A. G., Fleck, S. L., Collaco-Moraes, Y., Wyzydrag, L., Drummond, F. M., Connor, S. A., Satchell, C. S., Gunn, S., Delfino, M. A., Merlin, K., Mcginley, C., Neaton, J. D., George, M., Grund, B., Hogan, C., Miller, C., Roediger, M. P., Thackeray, L., Campbell, C., Lahart, C., Perlman, D., Rein, M., Dersimonian, R., Brody, B. A., Daar, E. S., Dubler, N. N., Fleming, T. R., Freeman, D. J., Kahn, J. P., Kim, K. M., Medoff, G., Modlin, J. F., Moellering, R., Murray, B. E., Robb, M. L., Scharfstein, D. O., Sugarman, J., Tsiatis, A., Tuazon, C., Zoloth, L., Belloso, W. H., Losso, M. H., Benetucci, J. A., Bogdanowicz, E. P., Cahn, P. E., Casiro, A. D., Cassetti, I., Contarelli, J. M., Corral, J. A., Crinejo, A., David, D. O., Ishida, M. T., Laplume, H. E., Lasala, M. B., Lupo, S. H., Masciottra, F., Michaan, M., Ruggieri, L., Salazar, E., Allworth, A. M., Anderson, J. S. C., Armishaw, J., Barnes, K., Chiam, A., Chuah, J. C. P., Curry, M. C., Dever, R. L., Donohue, W. A., Doong, N. C., Dwyer, D. E., Dyer, J., Eu, B., Ferguson, V. W., French, M. A. H., Garsia, R. J., Hudson, J. H., Jeganathan, S., Konecny, P., Mccormack, C. L., Mcmurchie, M., Moore, R. J., Moussa, M. B., Piper, M., Read, T., Roney, J. J., Shaw, D. R., Silvers, J., Smith, D. J., Street, A. C., Vale, R. J., Wendt, N. A., Wood, H., Youds, D. W., Zillman, J., Tozeau, V., de Roo, A., Leonard, P., Lynen, L., Moutschen, M., Pereira, L. C., Souza, T. N. L., Schechter, M., Zajdenverg, R., Almeida, M. M. T. B., Araujo, F., Bahia, F., Brites, C., Caseiro, M. M., Casseb, J., Etzel, A., Falco, G. G., Filho, E. C. J., Flint, S. R., Gonzales, C. R., Madruga, J. V. R., Passos, L. N., Reuter, T., Sidi, L. C., Toscano, A. L. C., Cherban, E., Conway, B., Dufour, C., Foster, A., Haase, D., Haldane, H., Klein, M., Lessard, B., Martel, A., Martel, C., Paradis, E., Schlech, W., Schmidt, S., Thompson, B., Vezina, S., Wolff Reyes, M. J., Northland, R., Hergens, L., Loftheim, I. R., Raukas, M., Justinen, J., Landman, R., Abel, S., Abgrall, S., Amat, K., Auperin, L., Barruet, R., Benalycherif, A., Benammar, N., Bentata, M., Besnier, J. M., Blanc, M., Cabie, A., Chavannet, P., Dargere, S., de la Tribonniere, X., Debord, T., Decaux, N., Delgado, J., Frixon-Marin, V., Genet, C., Gerard, L., Gilquin, J., Jeantils, V., Kouadio, H., Leclercq, P., Lelievre, J. -D., Michon, C. P., Nau, P., Pacanowski, J., Piketty, C., Salmon, D., Schmit, J. L., Serini, M. A., Tassi, S., Touam, F., Verdon, R., Weinbreck, P., Yazdanpanah, Y., Yeni, P., Bitsch, S., Bogner, J. R., Goebel, F. D., Lehmann, C., Lennemann, T., Potthof, A., Wasmuth, J. C., Wiedemeyer, K., Hatzakis, A., Touloumi, G., Antoniadou, A., Daikos, G. L., Dimitrakaki, A., Gargalianos-Kakolyris, P., Giannaris, M., Karafoulidou, A., Katsambas, A., Katsarou, O., Kontos, A. N., Kordossis, T., Lazanas, M. K., Panagopoulos, P., Paparizos, V., Papastamopoulos, V., Petrikkos, G., Skoutelis, A., Tsogas, N., Bergin, C. J., Mooka, B., Mamorksy, M. G., Agmon-Levin, N., Karplus, R., Shahar, E., Biglino, A., De Gioanni, M., Montroni, M., Raise, E., Honda, M., Ishisaka, M., Caplinskas, S., Uzdaviniene, V., Schmit, J. C., Mills, G. D., Blackmore, T., Masters, J. A., Morgan, J., Pithie, A., Brunn, J., Ormasssen, V., La Rosa, A., Guerra, O., Espichan, M., Gutierrez, L., Mendo, F., Salazar, R., Knytz, B., Kwiatkowski, J., Castro, R. S., Horta, A., Miranda, A. C., Pinto, I. V., Vera, J., Vinogradova, E., Yakovlev, A., Wood, R., Orrel, C., Arnaiz, J. A., Carrillo, R., Dalmau, D., Jordano, Q., Knobel, H., Larrousse, M., Moreno, J. S., Oretaga, E., Pena, J. N., Spycher, R., Bottone, S., Christen, A., Franc, C., Furrer, H. J., Gayet-Ageron, A., Genne, D., Hochstrasser, S., Moens, C., Nuesch, R., Ruxrungtham, K., Pumpradit, W., Dangthongdee, S., Kiertiburanakul, S., Klinbuayaem, V., Mootsikapun, P., Nonenoy, S., Piyavong, B., Prasithsirikul, W., Raksakulkarn, P., Gazzard, B. G., Ainsworth, J. G., Angus, B. J., Barber, T. J., Brook, M. G., Care, C. D., Chadwick, D. R., Chikohora, M., Churchill, D. R., Cornforth, D., Dockrell, D. H., Easterbrook, P. J., Fox, P. A., Gomez, P. A., Gompels, M. M., Harris, G. M., Herman, S., Jackson, A. G. A., Jebakumar, S. P. R., Kinghorn, G. R., Kuldanek, K. A., Larbalestier, N., Lumsden, M., Maher, T., Mantell, J., Muromba, L., Orkin, C. M., Palfreeman, A. J., Peters, B. S., Peto, T. E. A., Portsmouth, S. D., Rajamanoharan, S., Ronan, A., Schwenk, A., Slinn, M. A., Stroud, C. J., Thomas, R. C., Wansbrough-Jones, M. H., Whiles, H. J., White, D. J., Williams, E., Williams, I. G., Acosta, E. A., Adamski, A., Antoniskis, D., Aragon, D. R., Barnett, B. J., Baroni, C., Barron, M., Baxter, J. D., Beers, D., Beilke, M., Bemenderfer, D., Bernard, A., Besch, C. L., Bessesen, M. T., Bethel, J. T., Blue, S., Blum, J. D., Boarden, S., Bolan, R. K., Borgman, J. B., Brar, I., Braxton, B. K., Bredeek, U. F., Brennan, R., Britt, D. E., Bulgin-Coleman, D., Bullock, D. E., Campbell, B., Caras, S., Carroll, J., Casey, K. K., Chiang, F., Cindrich, R. B., Clark, C., Cohen, C., Coley, J., Condoluci, D. V., Contreras, R., Corser, J., Cozzolino, J., Daley, L., Dandridge, D., D'Antuono, V., Darcourt Rizo Patron, J. G., Dehovitz, J. A., Dejesus, E., Desjardin, J., Dietrich, C., Dolce, E., Erickson, D., Faber, L. L., Falbo, J., Farrough, M. J., Farthing, C. F., Ferrell-Gonzalez, P., Flynn, H., Frank, M., Freeman, K. F., French, N., Fujita, N., Gahagan, L., Gilson, I., Goetz, M. B., Goodwin, E., Guity, C. K., Gulick, P., Gunderson, E. R., Hale, C. M., Hannah, K., Henderson, H., Hennessey, K., Henry, W. K., Higgins, D. T., Hodder, S. L., Horowitz, H. W., Howe-Pittman, M., Hubbard, J., Hudson, R., Hunter, H., Hutelmyer, C., Insignares, M. T., Jackson, L., Jenny, L., Johnson, D. L., Johnson, G., Johnson, J., Kaatz, J., Kaczmarski, J., Kagan, S., Kantor, C., Kempner, T., Kieckhaus, K., Kimmel, N., Klaus, B. M., Koeppe, J. R., Koirala, J., Kopka, J., Kostman, J. R., Kozal, M. J., Kumar, A., Lampiris, H., Lamprecht, C., Lattanzi, K. M., Lee, J., Leggett, J., Long, C., Loquere, A., Loveless, K., Lucasti, C. J., Macveigh, M., Makohon, L. H., Markowitz, N. P., Marks, C., Martorell, C., Mcfeaters, E., Mcgee, B., Mcintyre, D. M., Mcmanus, E., Melecio, L. G., Melton, D., Mercado, S., Merrifield, E., Mieras, J. A., Mogyoros, M., Moran, F. M., Murphy, K., Mutic, S., Nadeem, I., Nadler, J. P., Ognjan, A., O'Hearn, M., O'Keefe, K., Okhuysen, P. C., Oldfield, E., Olson, D., Orenstein, R., Ortiz, R., Parpart, F., Pastore-Lange, V., Paul, S., Pavlatos, A., Pearce, D. D., Pelz, R., Peterson, S., Pitrak, D., Powers, S. L., Pujet, H. C., Raaum, J. W., Ravishankar, J., Reeder, J., Reilly, N. A., Reyelt, C., Riddell, J., Rimland, D., Robinson, M. L., Rodriguez, A. E., Rodriguez-Barradas, M. C., Rodriguez Derouen, V., Rosmarin, C., Rossen, W. L., Rouff, J. R., Sampson, J. H., Sands, M., Savini, C., Schrader, S., Schulte, M. M., Scott, R., Seedhom, H., Sension, M., Sheble-Hall, A., Shuter, J., Slater, L. N., Slotten, R., Smith, M., Snap, S., States, D. M., Stringer, G., Summers, K. K., Swanson, K., Sweeton, I. B., Szabo, S., Telzak, E. E., Thompson, M. A., Thompson, S., Ting Hong Bong, C., Vaccaro, A., Vasco, L. M., Vecino, I., Verlinghieri, G. K., Visnegarwala, F., Wade, B. H., Weis, S. E., Weise, J. A., Weissman, S., Wilkin, A. M., Witter, J. H., Wojtusic, L., Wright, T. J., Yeh, V., Young, B., Zeana, C., Zeh, J., Savio, E., Vacarezza, M., and Cauda R. (ORCID:0000-0002-1498-4229)

Abstract

Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7–6.7; median follow-up 6.1 y, range 0.3–9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was −2 (interquartile range –4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0–4, 103 events) and high risk groups (risk score ≥ 5, 505 events)

Published
2015

11. Dynamics of adaptive and innate immunity in patients treated during primary human immunodeficiency virus infection: results from Maraviroc in HIV Acute Infection (MAIN) randomized clinical trial

Author

Ripa, M., primary, Pogliaghi, M., additional, Chiappetta, S., additional, Galli, L., additional, Pensieroso, S., additional, Cavarelli, M., additional, Scarlatti, G., additional, De Biasi, S., additional, Cossarizza, A., additional, De Battista, D., additional, Malnati, M., additional, Lazzarin, A., additional, Nozza, S., additional, and Tambussi, G., additional

Published
2015
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12. Efficacy and safety of an NRTI-sparing regimen in antiretroviral-naïve HIV-infected patients: once-daily maraviroc plus lopinavir/ritonavir

Author

Nozza, S., Galli, L., Di Pietro, M., Mazzotta, F., Canducci, F., Pogliaghi, M., Chiappetta, S., Galli, A., Rusconi, V., Salpietro, S., Tambussi, G., and Lazzarin, A.

Subjects
Maraviroc -- Dosage and administration -- Testing, Practice guidelines (Medicine) -- Evaluation, Lopinavir -- Dosage and administration -- Testing, Ritonavir -- Dosage and administration -- Testing, HIV infection -- Drug therapy, Health
Abstract

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Current guidelines recommend three drug combinations to treat antiretroviral naïve HIV‐infected patients; some data of novel strategies with NRTI‐sparing regimen in this setting are now available [1,2]. The study compares [...]

Published
2010
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14. Dynamics of adaptive and innate immunity inpatients treated during primary human immunodeficiency virus infection: Results from Maraviroc in HIV Acute Infection (MAIN) randomized clinical trial

Author

Simone Pensieroso, Marco Ripa, Laura Galli, D. De Battista, Mauro S. Malnati, Stefania Chiappetta, Silvia Nozza, Adriano Lazzarin, Gabriella Scarlatti, Andrea Cossarizza, Manuela Pogliaghi, Giuseppe Tambussi, S. De Biasi, Mariangela Cavarelli, Ripa, M., Pogliaghi, M., Chiappetta, S., Galli, L., Pensieroso, S., Cavarelli, M., Scarlatti, G., De Biasi, S., Cossarizza, A., De Battista, D., Malnati, M., Lazzarin, A., Nozza, S., and Tambussi, G.

Subjects
Male, Myeloid, HIV Infections, Adaptive Immunity, Dendritic cells, Maraviroc, chemistry.chemical_compound, Antiretroviral Therapy, Highly Active, Innate, HIV Infection, Prospective Studies, B cell, natural killer cells, Medicine (all), Primary human immunodeficiency virus type 1 infection, General Medicine, Acquired immune system, medicine.anatomical_structure, Infectious Diseases, Natural killer cells, Female, primary human immunodeficiency virus type 1 infection, Human, Adult, Microbiology (medical), B cells, Immune activation, Anti-HIV Agents, Cyclohexanes, Dendritic Cells, HIV, Humans, Lymphocyte Subsets, Triazoles, Immunity, Innate, Natural killer cell, Antiretroviral Therapy, chemical and pharmacologic phenomena, CD16, Biology, Dendritic Cell, immune activation, Cyclohexane, medicine, Highly Active, Innate immune system, Immunity, Anti-HIV Agent, Dendritic cell, Virology, Prospective Studie, chemistry, Lymphocyte Subset, Immunology, Triazole, CD8
Abstract

We evaluated the dynamics of innate and adaptive immunity in patients treated with combined antiretroviral therapy (cART) during primary human immunodeficiency virus infection (PHI), enrolled in a prospective randomized trial (MAIN, EUDRACT 2008-007004-29). After 48 weeks of cART, we documented a reduction in activated B cells and CD8 + T cells. Natural killer cell and dendritic cell frequencies were measured and a decrease in CD16 + CD56 dim with a reciprocal rise in CD56 high natural killer cells and an increase in myeloid and plasmacytoid dendritic cells were recorded. In conclusion, 48 weeks of cART during PHI showed significant benefits for both innate and adaptive immunity.

Published
2015

15. Durability and safety of a novel salvage therapy in R5-tropic HIV-infected patients: Maraviroc, raltegravir, etravirine

Author

Antonella Castagna, Andrea Galli, Alba Bigoloni, Silvia Nozza, Francesca Cossarini, Stefania Salpietro, Liviana Della Torre, Laura Galli, Adriano Lazzarin, Manuela Pogliaghi, Giuseppe Tambussi, Gianotti Nicola, Nozza, S., Galli, L., Bigoloni, A., Nicola, G., Pogliaghi, M., Cossarini, F., Salpietro, S., Galli, A., Torre, L. D., Tambussi, G., Lazzarin, A., and Castagna, A.

Subjects
Adult, Male, Anti-HIV Agents, Etravirine, Salvage therapy, HIV Infections, Maraviroc, chemistry.chemical_compound, Cyclohexanes, Antiretroviral Therapy, Highly Active, Raltegravir Potassium, Nitriles, Medicine, Hiv infected patients, Humans, Pharmacology (medical), Salvage Therapy, business.industry, Middle Aged, Triazoles, Viral Load, Raltegravir, Virology, Pyrrolidinones, CD4 Lymphocyte Count, Pyridazines, Infectious Diseases, Pyrimidines, Treatment Outcome, chemistry, RNA, Viral, Female, business, medicine.drug
Published
2011

16. Maraviroc 150 mg daily plus lopinavir/ritonavir, a nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimen for HIV-infected naive patients: 48-week final results of VEMAN study

Author

S, Nozza, L, Galli, A, Antinori, S, Chiappetta, F, Mazzotta, M, Zaccarelli, S, Ottou, D, De Battista, M, Pogliaghi, M, Di Pietro, M, Malnati, M, Ripa, S, Bonora, A, Lazzarin, Mauro, Zaccarelli, Nozza, S., Galli, L., Antinori, A., Chiappetta, S., Mazzotta, F., Zaccarelli, M., Ottou, S., De Battista, D., Pogliaghi, M., Di Pietro, M., Malnati, M., Ripa, M., Bonora, S., and Lazzarin, A.

Subjects
Male, Lopinavir/ritonavir, HIV Infections, Pharmacology, Gastroenterology, Lopinavir, Maraviroc, chemistry.chemical_compound, Drug Combination, Antiretroviral Therapy, Highly Active, HIV Infection, Prospective Studies, Antiretroviral therapy, Human immunodeficiency virus, Naive patients, Nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimen, Microbiology (medical), Infectious Diseases, Reverse-transcriptase inhibitor, virus diseases, General Medicine, Viral Load, Drug Combinations, Treatment Outcome, Female, Human, medicine.drug, Adult, medicine.medical_specialty, Anti-HIV Agents, Emtricitabine, Virus, Cyclohexane, Cyclohexanes, Internal medicine, medicine, Humans, Human immunodeficiency viru, Ritonavir, business.industry, Anti-HIV Agent, Triazoles, CD4 Lymphocyte Count, Prospective Studie, Regimen, chemistry, DNA, Viral, HIV-1, Triazole, Naive patient, business
Abstract

Non-conventional strategies with nucleoside/nucleotide reverse transcriptase inhibitor-sparing regimens in antiretroviral naive human immunodeficiency virus (HIV) -infected patients have been explored in clinical trials. A prospective, open-label, randomized (1:1), multicentre, proof-of-concept trial (VEMAN study, EUDRACT number 2008-006287-11) was conducted assigning HIV-infected naive patients to once-daily maraviroc plus lopinavir/ritonavir (MVC group) or to tenofovir/emtricitabine plus lopinavir/ritonavir (TDF/FTC group). Clinical and laboratory data were collected at baseline, and after 4, 12, 24, 36 and 48 weeks with the objective to evaluate the 48-week virological and immunological efficacy. HIV-1 DNA load and CD4(+) T-cell subsets were analysed on frozen peripheral blood mononuclear cells collected at baseline, 4 and 48 weeks to explore the trend in HIV reservoirs. Fifty patients were randomized and included in the analysis. During follow up, HIV-1 RNA decreased similarly in both groups and, at week 48, all patients in the MVC group and 22/24 (96%) in the TDF/FTC group had < 50 copies/ml of HIV-1 RNA. CD4(+) trend during follow up was higher in maraviroc-treated patients (MVC group: 286 (183-343) versus TDF/FTC group: 199 (125-285); Mann-Whitney U-test: p 0.033). A significant 48-week increase of CCR5(+) CD4(+) T cells and CD4(+) effector memory cells was observed among maraviroc-treated patients (Wilcoxon signed rank test: p 0.016 and p 0.007, respectively). No significant variations were found in naive and central memory CD4(+) T cells. Among naive patients with an R5 virus, treatment with maraviroc and lopinavir/ritonavir was shown to provide a virological response compared to a triple therapy and a greater immunological benefit.

Published
2015

17. Real-world experience with meropenem/vaborbactam for the treatment of infections caused by ESBL-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae.

Author

Tiseo G, Galfo V, Riccardi N, Suardi LR, Pogliaghi M, Giordano C, Leonildi A, Barnini S, and Falcone M

Abstract

Purpose: Real-world experience with meropenem/vaborbactam (M/V) is limited. Our aim is to report a clinical experience of M/V in the treatment of resistant Gram-negative bacilli., Methods: This is a prospective observational study including patients hospitalized in the University Hospital of Pisa (March 2021-Jan 2023) with infections by both extended-spectrum β-lactamases (ESBL)-producing Enterobacterales and carbapenem-resistant Klebsiella pneumoniae (Kp) treated with M/V. The primary outcome measure was clinical success, defined as a composite of survival, resolution of signs and symptoms and absence of microbiological failure at day 30 from infection onset. A multivariable regression analysis was performed to identify factors associated with clinical failure. Odds ratio (OR) with 95% confidence intervals (CI) was calculated., Results: A total of 104 patients who received M/V were included: 24/104 (23.1%) infections were caused by ESBL non-hypervirulent Enterobacterales, 17/104 (16.3%) by ESBL-producing hypervirulent Klebsiella pneumoniae (hvKp) and 63/104 (60.6%) by CRE. The most common infections were bloodstream infections, followed by urinary tract infections, hospital-acquired pneumonia, intra-abdominal infections and others. Septic shock occurred in 16/104 (15.4%) patients. Clinical success was achieved in 77% of patients, and 30-day mortality rate was 15.4%. In patients with KPC-producing Kp infections, clinical success and 30-day mortality rates were 82% and 11.5%, respectively. On multivariable analysis, SOFA score (OR 1.32, 95% CI 1.02-1.7, p=0.032) was independently associated with clinical failure, while source control (OR 0.16, 95% CI 0.03-0.89, p=0.036) was protective., Conclusions: M/V is a promising therapeutic option against infections caused by difficult-to-treat ESBL-producing Enterobacterales and CR-Kp., (© 2024. The Author(s).)

Published
2024
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18. Efficacy and Safety of Nirmatrelvir/Ritonavir, Molnupiravir, and Remdesivir in a Real-World Cohort of Outpatients with COVID-19 at High Risk of Progression: The PISA Outpatient Clinic Experience.

Author

Tiseo G, Barbieri C, Galfo V, Occhineri S, Matucci T, Almerigogna F, Kalo J, Sponga P, Cesaretti M, Marchetti G, Forniti A, Caroselli C, Ferranti S, Pogliaghi M, Polidori M, Fabiani S, Verdenelli S, Tagliaferri E, Riccardi N, Suardi LR, Carmignani C, Batini S, Puccetti L, Iapoce R, Menichetti F, and Falcone M

Abstract

Introduction: Different antivirals are available for the treatment of outpatients with COVID-19. Our aim was to describe a real-world experience of outpatient management of COVID-19 subjects at high risk of progression., Methods: This prospective observational study conducted in the University Hospital of Pisa (January 2022-July 2022) included consecutive COVID-19 outpatients with at least one risk factor for disease progression. Patients received nirmatrelvir/ritonavir, molnupiravir, or 3-day remdesivir, according to the Italian Medicines Agency (AIFA) indications. All patients were followed up until 30 days from the first positive nasopharyngeal swab. The primary endpoint was a composite of death or hospitalization. Secondary endpoints were occurrence of adverse events and a negative test within 10 days from the first positive test. Multivariable analysis was performed to identify factors associated with death or hospitalization., Results: Overall, 562 outpatients were included: 114 (20.3%) received molnupiravir, 252 (44.8%) nirmatrelvir/ritonavir, and 196 (34.9%) 3-day remdesivir. The composite endpoint occurred in 2.5% of patients and was more frequent in patients treated with remdesivir (5.1%) compared with molnupiravir (1.8%) or nirmatrelvir/ritonavir (0.8%, ANOVA among groups p = 0.012). On multivariable Cox regression analysis, presence of ≥ 3 comorbidities, hematological disease, gastrointestinal symptoms, and each-day increment from symptoms onset were factors associated with death or hospitalization, while antiviral treatment was not a predictor. Adverse events occurred more frequently in the nirmatrelvir/ritonavir group (49.2%). Nirmatrelvir/ritonavir compared with remdesivir was associated with a higher probability of having a negative test within 10 days from the first positive one., Conclusion: Death or hospitalization did not differ among high-risk COVID-19 outpatients treated with currently available antivirals. Safety and time to a negative test differed among the three drugs., (© 2022. The Author(s).)

Published
2023
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19. Hepatitis B Virus-Hepatitis D Virus mother-to-child co-transmission: A retrospective study in a developed country.

Author

Sellier PO, Maylin S, Brichler S, Berçot B, Lopes A, Chopin D, Pogliaghi M, Munier AL, Delcey V, Simoneau G, Evans J, Gordien E, Simon F, and Bergmann JF

Subjects
Adult, Child, Child, Preschool, Coinfection drug therapy, DNA, Viral blood, Developed Countries, Female, Hepatitis Antibodies blood, Hepatitis B Surface Antigens blood, Hepatitis B virus, Hepatitis B, Chronic drug therapy, Hepatitis D drug therapy, Hepatitis Delta Virus, Humans, Immunization, Passive statistics & numerical data, Infant, Male, Paris, Pregnancy, Retrospective Studies, Viral Load, Young Adult, Antiviral Agents therapeutic use, Hepatitis B, Chronic transmission, Hepatitis D transmission, Infectious Disease Transmission, Vertical prevention & control, Infectious Disease Transmission, Vertical statistics & numerical data
Abstract

Background & Aims: Hepatitis B Virus (HBV) DNA during chronic infection can reach levels at which mother-to-child (MTC) transmission frequently occurs despite passive-active immunization of newborns. Hepatitis D Virus (HDV) RNA can reach high levels, we assessed HBV/HDV MTC co-transmission., Methods: Monocentric retrospective study (registered in ClinicalTrials.gov (NCT02044055)), after informed consent in HBV/HDV co-infected women pregnant between 01/01/2004 and 01/01/2015 in Paris, France. The children were tested when 24 months of age or older., Results: Twenty-two (3%) of 742 HBV infected women, HDV co-infected, gave birth to 54 children during the study period. HBV DNA was above 5 Log 10 I.U/mL in 10 pregnancies previous any treatment, with HDV RNA of less than 2.3 Log 10 I.U/mL. HDV RNA was above 5 Log 10 I.U/mL in eight pregnancies previous any treatment, with HBV DNA of less than 1.5 Log 10 I.U/mL. Inverse patterns of HBV DNA and HDV RNA were observed in 17 of 35 (49%) pregnancies: 13 (76%) received no HBV treatment; four (24%) were treated. HBV DNA was under 5 Log 10 I.U/mL in 46 of the 50 assessed women (92%) at birth. Of the 36 assessed children, given passive-active immunization, 24 (66%) were protected, 10 (28%) were neither infected nor protected, one was chronically HBV infected, and one had a past HBV infection. HDV Ab was negative in the 36 children., Conclusions: These results suggest that HBV/HDV MTC co-transmission is exceptional. Studies are needed, mainly in developing countries., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Published
2018
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20. IgG4-related disease and ANCA positivity: an overlap syndrome?

Author

Bravais J, Pogliaghi M, Polivka M, Sène D, and Roriz M

Subjects
Adult, Biopsy, Dacryocystitis etiology, Diagnosis, Differential, Female, Granulomatosis with Polyangiitis blood, Granulomatosis with Polyangiitis complications, Humans, Lung pathology, Lymphadenopathy diagnostic imaging, Lymphadenopathy etiology, Tomography, X-Ray Computed, Antibodies, Antineutrophil Cytoplasmic blood, Granulomatosis with Polyangiitis diagnosis, Immunoglobulin G blood, Lung diagnostic imaging
Published
2017
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21. Maraviroc in addition to cART during primary HIV infection: Results from MAIN randomized clinical trial and 96-weeks follow-up.

Author

Ripa M, Pogliaghi M, Chiappetta S, Nozza S, Soria A, Coppalini G, Rovelli C, and Tambussi G

Subjects
Adult, CD4 Lymphocyte Count, Female, Follow-Up Studies, Humans, Male, Maraviroc, Middle Aged, Nerve Tissue Proteins, RNA, Viral blood, Treatment Outcome, Viral Load, Anti-Retroviral Agents therapeutic use, Antiretroviral Therapy, Highly Active methods, CCR5 Receptor Antagonists therapeutic use, Cyclohexanes therapeutic use, HIV Infections drug therapy, Triazoles therapeutic use
Abstract

Background: Multi-targeted treatment strategies including maraviroc (MVC) during Primary HIV Infection (PHI) may benefit from the immune-modulatory properties of this CCR5-inhibitor., Objectives: We conducted a proof-of-concept clinical trial aimed at assessing whether maraviroc in addition of a combination antiretroviral therapy (cART) initiated during PHI would improve immunological and virological parameters., Study Design: The MAIN (Maraviroc in HIV Acute INfection) study was a randomized open-label clinical trial (EUDRACT number: 2008-007004-29) which enrolled 29 patients with PHI. Subjects were randomly assigned to receive cART-only (cART), cART+8 weeks of MVC (ST-MVC) or cART+48 weeks of MVC (LT-MVC), regardless of predicted co-receptor usage. After 48 weeks patients in ST-MVC and LT-MVC groups discontinued MVC. Patients were evaluated at week 48 and at week 96 of follow-up to assess differences in CD4 T-cell gain and plasma HIV-RNA., Results: Twenty-nine patients were enrolled. Seven patients (24%) had a predicted CXCR4 co-receptor usage. At week 48, 27 patients (93.1%) reached HIV-RNA<50cps/mL. Median CD4 T-cell count increase was 313 cells/μL (p<0.001, Wilcoxon signed-rank test). At multivariate linear regression analysis, LT-MVC arm had the greatest CD4 T-cell increase, while patients in ST-MVC arm had the least gain in CD4 T-cells (p=0.007). At week 96, multivariate analysis showed no associations between former treatment arm and CD4 T-cell gain., Conclusions: The MAIN study showed that MVC for 48 weeks in addition to cART during PHI was able to enhance CD4 T-cell gain, regardless of co-receptor usage. After MVC discontinuation, the difference between treatment arms was lost., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Published
2016
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23. Beneficial Effects of cART Initiated during Primary and Chronic HIV-1 Infection on Immunoglobulin-Expression of Memory B-Cell Subsets.

Author

Pogliaghi M, Ripa M, Pensieroso S, Tolazzi M, Chiappetta S, Nozza S, Lazzarin A, Tambussi G, and Scarlatti G

Subjects
Adult, Female, Gene Expression Regulation drug effects, Gene Expression Regulation immunology, Humans, Immunoglobulin D immunology, Immunoglobulin M immunology, Male, Middle Aged, Time Factors, Anti-Retroviral Agents administration & dosage, B-Lymphocyte Subsets immunology, B-Lymphocyte Subsets pathology, HIV Infections drug therapy, HIV Infections immunology, HIV Infections pathology, HIV-1, Immunologic Memory drug effects, Plasma Cells immunology, Plasma Cells pathology
Abstract

Introduction: During HIV-1 infection the B-cell compartment undergoes profound changes towards terminal differentiation, which are only partially restored by antiretroviral therapy (cART)., Materials and Methods: To investigate the impact of infection as early as during primary HIV-1 infection (PHI) we assessed distribution of B-cell subsets in 19 PHI and 25 chronic HIV-1-infected (CHI) individuals before and during 48 weeks of cART as compared to healthy controls (n = 23). We also analysed Immunoglobulin-expression of memory B-cell subsets to identify alterations in Immunoglobulin-maturation., Results: Determination of B-cell subsets at baseline showed that total and Naive B-cells were decreased whereas Activated Memory (AM), Tissue-like Memory (TLM) B-cells and Plasma cells were increased in both PHI and CHI patients. After 4 weeks of cART total B-cells increased, while AM, TLM B-cells and Plasma cells decreased, although without reaching normal levels in either group of individuals. This trend was maintained until week 48, though only total B-cells normalized in both PHI and CHI. Resting Memory (RM) B-cells were preserved since baseline. This subset remained stable in CHI, while was expanded by an early initiation of cART during PHI. Untreated CHI patients showed IgM-overexpression at the expenses of switched (IgM-IgD-) phenotypes of the memory subsets. Interestingly, in PHI patients a significant alteration of Immunoglobulin-expression was evident at BL in TLM cells, and after 4 weeks, despite treatment, in AM and RM subsets. After 48 weeks of therapy, Immunoglobulin-expression of AM and RM almost normalized, but remained perturbed in TLM cells in both groups., Conclusions: In conclusion, aberrant activated and exhausted B-cell phenotypes rose already during PHI, while most of the alterations in Ig-expression seen in CHI appeared later, despite 4 weeks of effective cART. After 48 weeks of cART B-cell subsets distribution improved although without full normalization, while Immunoglobulin-expression normalized among AM and RM, remaining perturbed in TLM B-cells of PHI and CHI.

Published
2015
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24. The tyrosine kinase inhibitor Dasatinib blocks in-vitro HIV-1 production by primary CD4+ T cells from HIV-1 infected patients.

Author

Pogliaghi M, Papagno L, Lambert S, Calin R, Calvez V, Katlama C, and Autran B

Subjects
Cells, Cultured, Dasatinib, HIV Infections immunology, HIV Infections virology, Humans, Anti-HIV Agents pharmacology, CD4-Positive T-Lymphocytes drug effects, CD4-Positive T-Lymphocytes virology, HIV-1 drug effects, HIV-1 physiology, Pyrimidines pharmacology, Thiazoles pharmacology, Virus Replication drug effects
Abstract

HIV reservoirs persistence despite antiretroviral therapy (ART) might be related to persistent immune activation and residual HIV production, requiring further therapeutic strategies. We demonstrated that the tyrosine kinase inhibitor (TKI) Dasatinib, used for chronic myeloid leukaemia, significantly blocks in vitro HIV1 production by 3.4 logs in HIV1-infected primary CD4 T lymphocytes, by inhibiting cell activation and proliferation, without cell toxicity. This molecule deserves to be investigated further for HIV cure strategies to hinder persistent immune activation and residual viral production.

Published
2014
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25. Levels of soluble endothelial protein C receptor are associated with CD4+ changes in Maraviroc-treated HIV-infected patients.

Author

Nozza S, Pogliaghi M, Chiappetta S, Spagnuolo V, Fontana G, Razzari C, Tambussi G, and Faioni EM

Subjects
Adult, Aged, Antigens, CD blood, Biomarkers blood, Blood Coagulation drug effects, CD4 Lymphocyte Count, Endothelial Protein C Receptor, Endothelium, Vascular immunology, Endothelium, Vascular injuries, Endothelium, Vascular metabolism, Female, Follow-Up Studies, HIV Infections blood, Humans, Male, Maraviroc, Middle Aged, Receptors, Cell Surface blood, Antigens, CD immunology, CCR5 Receptor Antagonists administration & dosage, Cyclohexanes administration & dosage, HIV Infections drug therapy, HIV Infections immunology, Receptors, Cell Surface immunology, Triazoles administration & dosage
Abstract

Background: Inflammation is a key feature of HIV infection and is correlated with long-term negative cardiovascular outcomes. Therapy-induced increases in CD4(+) cell counts can control inflammation, as shown by decreases of coagulation and inflammation markers during efficacious therapy. Maraviroc, a CCR5-antagonist, has resulted in larger increases in CD4(+) counts both in naïve and experienced subjects compared to traditional antiretroviral therapy., Objectives and Methods: To examine if a member of the protein C anticoagulant and anti-inflammatory pathway, and marker of coagulation and inflammation, the soluble endothelial protein C receptor, is modified by infection and therapy-related variables in patients treated with Maraviroc. Endothelial protein C receptor, together with other established markers of inflammation and coagulation (CRP, IL-6, D-dimer and soluble thrombomodulin) was studied in 43 patients on traditional antiretroviral therapy and in 45 on Maraviroc during 48 weeks of follow-up., Results: Soluble endothelial protein C receptor was the only marker that could discriminate at least partially between patients with a good response to Maraviroc and patients who did not respond with an adequate increase in CD4(+) cell counts (more than 500 cells/µL by week 48)., Conclusions: Elevated levels of soluble endothelial protein C receptor, a sensitive marker of endothelial damage, indicated a low level of inflammation and coagulation activation in Maraviroc treated patients not picked up by other widely used markers. Persistent elevated levels of this marker at 48 weeks from beginning of treatment with Maraviroc were related to a poor increase in CD4(+) cells.

Published
2012
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26. Durability and safety of a novel salvage therapy in R5-tropic HIV-infected patients: maraviroc, raltegravir, etravirine.

Author

Nozza S, Galli L, Bigoloni A, Nicola G, Pogliaghi M, Cossarini F, Salpietro S, Galli A, Della Torre L, Tambussi G, Lazzarin A, and Castagna A

Subjects
Adult, Anti-HIV Agents administration & dosage, Anti-HIV Agents adverse effects, Antiretroviral Therapy, Highly Active methods, CD4 Lymphocyte Count, Cyclohexanes adverse effects, Female, Humans, Male, Maraviroc, Middle Aged, Nitriles, Pyridazines adverse effects, Pyrimidines, Pyrrolidinones adverse effects, RNA, Viral blood, Raltegravir Potassium, Salvage Therapy methods, Treatment Outcome, Triazoles adverse effects, Viral Load, Antiretroviral Therapy, Highly Active adverse effects, Cyclohexanes administration & dosage, HIV Infections drug therapy, Pyridazines administration & dosage, Pyrrolidinones administration & dosage, Salvage Therapy adverse effects, Triazoles administration & dosage
Published
2011
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