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10. Natural History of α-Chain Disease and the So-called Mediterranean Lymphoma

Author

Rambaud, J. C., Galian, A., Matuchansky, C., Danon, F., Preud’Homme, J. L., Brouet, J. C., Seligmann, M., Allfrey, V. G., editor, Allgöwer, M., editor, Bauer, K. H., editor, Berenblum, I., editor, Bergel, F., editor, Bernard, J., editor, Bernhard, W., editor, Blokhin, N. N., editor, Bock, H. E., editor, Braun, W., editor, Bucalossi, P., editor, Chaklin, A. V., editor, Chorazy, M., editor, Cunningham, G. J., editor, Della Porta, G., editor, Denoix, P., editor, Dulbecco, R., editor, Eagle, H., editor, Eker, R., editor, Good, R. A., editor, Grabar, P., editor, Harris, R. J. C., editor, Hecker, E., editor, Herbeuval, R., editor, Higginson, J., editor, Hueper, W. C., editor, Isliker, H., editor, Kieler, J., editor, Kirsten, W. H., editor, Klein, G., editor, Koprowski, H., editor, Koss, L. G., editor, Martz, G., editor, Mathé, G., editor, Mühlbock, O., editor, Nakahara, W., editor, Old, L. J., editor, Potter, V. R., editor, Sabin, A. B., editor, Sachs, L., editor, Saxén, E. A., editor, Schmidt, C. G., editor, Spiegelman, S., editor, Szybalski, W., editor, Tagnon, H., editor, Taylor, R. M., editor, Tissières, A., editor, Uehlinger, E., editor, Wissler, R. W., editor, Rentchnick, P., editor, Mathé, Georges, editor, Seligmann, Maxime, editor, and Tubiana, Maurice, editor

Published
1978
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11. Human T-Derived Lymphoproliferative Diseases

Author

Brouet, J. C., Preud’Homme, J. L., Flandrin, G., Seligmann, M., Allfrey, V. G., editor, Allgöwer, M., editor, Bauer, K. H., editor, Berenblum, I., editor, Bergel, F., editor, Bernard, J., editor, Bernhard, W., editor, Blokhin, N. N., editor, Bock, H. E., editor, Braun, W., editor, Bucalossi, P., editor, Chaklin, A. V., editor, Chorazy, M., editor, Cunningham, G. J., editor, Della Porta, G., editor, Denoix, P., editor, Dulbecco, R., editor, Eagle, H., editor, Eker, R., editor, Good, R. A., editor, Grabar, P., editor, Harris, R. J. C., editor, Hecker, E., editor, Herbeuval, R., editor, Higginson, J., editor, Hueper, W. C., editor, Isliker, H., editor, Kieler, J., editor, Kirsten, W. H., editor, Klein, G., editor, Koprowski, H., editor, Koss, L. G., editor, Martz, G., editor, Mathé, G., editor, Mühlbock, O., editor, Nakahara, W., editor, Old, L. J., editor, Potter, V. R., editor, Sabin, A. B., editor, Sachs, L., editor, Saxén, E. A., editor, Schmidt, C. G., editor, Spiegelman, S., editor, Szybalski, W., editor, Tagnon, H., editor, Taylor, R. M., editor, Tissières, A., editor, Uehlinger, E., editor, Wissler, R. W., editor, Rentchnick, P., editor, Mathé, Georges, editor, Seligmann, Maxime, editor, and Tubiana, Maurice, editor

Published
1978
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12. Surface Cell Markers in Human Lymphoid Malignancies

Author

Seligmann, M., Preud’homme, J. L., Brouet, J. C., Allfrey, V. G., editor, Allgöwer, M., editor, Bauer, K. H., editor, Berenblum, I., editor, Bergel, F., editor, Bernard, J., editor, Bernhard, W., editor, Blokhin, N. N., editor, Bock, H. E., editor, Braun, W., editor, Bucalossi, P., editor, Chaklin, A. V., editor, Chorazy, M., editor, Cunningham, G. J., editor, Della Porta, G., editor, Denoix, P., editor, Dulbecco, R., editor, Eagle, H., editor, Eker, R., editor, Good, R. A., editor, Grabar, P., editor, Hamperl, H., editor, Harris, R. J. C., editor, Hecker, E., editor, Herbeuval, R., editor, Higginson, J., editor, Hueper, W. C., editor, Isliker, H., editor, Kieler, J., editor, Klein, G., editor, Koprowski, H., editor, Koss, L. G., editor, Martz, G., editor, Mathé, G., editor, Mühlbock, O., editor, Nakahara, W., editor, Old, L. J., editor, Potter, V. R., editor, Sabin, A. B., editor, Sachs, L., editor, Saxén, E. A., editor, Schmidt, C. G., editor, Spiegelman, S., editor, Szybalski, W., editor, Tagnon, H., editor, Taylor, R. M., editor, Tissières, A., editor, Uehlinger, E., editor, Wissler, R. W., editor, Rentchnick, P., editor, Mathé, Georges, editor, Florentin, Irène, editor, and Simmler, Marie-Christine, editor

Published
1976
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13. Primary Immunodeficiencies: Current Findings and Concepts

Author

Seligmann, M., Melchers, Fritz, editor, Albert, E. D., editor, von Boehmer, H., editor, Dierich, M. P., editor, Du Pasquier, L., editor, Eichmann, K., editor, Gemsa, D., editor, Götze, O., editor, Kalden, J. R., editor, Kaufmann, S. H. E., editor, Kirchner, H., editor, Resch, K., editor, Riethmüller, G., editor, Schimpl, A., editor, Sorg, C., editor, Steinmetz, M., editor, Wagner, H., editor, and Zachau, H. G., editor

Published
1989
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14. Primary Antibody Deficiencies

Author

Cooper, M. D., Lawton, A. R., Preud’homme, J. L., Seligmann, M., Cooper, Max D., editor, Lawton, A. R., editor, Miescher, P. A., editor, and Mueller-Eberhard, H. J., editor

Published
1979
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15. Concorde: MRC/ANRS randomised double-blind controlled trial of immediate and deferred zidovudine in symptom-free HIV infection. Concorde Coordinating Committee

Author

SELIGMANN, M, WARRELL, D, ABOULKER, J, CARBON, C, DARBYSHIRE, J, DORMONT, J, ESCHWEGE, E, GIRLING, D, JAMES, D, LEVY, J, PETO, T, SCHWARZ, D, STONE, A, WELLER, I, WITHNALL, R, GELMON, K, LAFON, E, SWART, A, ABER, V, BABIKER, A, LHORO, S, NUNN, A, and VRAY, M

Abstract

Concorde is a double-blind randomised comparison of two policies of zidovudine treatment in symptom-free individuals infected with human immunodeficiency virus (HIV): (a) immediate zidovudine from the time of randomisation (Imm); and (b) deferred zidovudine (Def) until the onset of AIDS-related complex (ARC) or AIDS (CDC group IV disease) or the development of persistently low CD4 cell counts if the clinician judged that treatment was indicated. Between October, 1988, and October, 1991, 1749 HIV-infected individuals from centres in the UK, Ireland, and France were randomly allocated to zidovudine 250 mg four times daily (877 Imm) or matching placebo (872 Def). Follow-up was to death or Dec 31, 1992 (total 5419 person-years; median 3.3 years) and only 7% of the 1749 had not had a full clinical assessment after July 1, 1992. Of those allocated to the Def group, 418 started zidovudine at some time during the trial, 174 (42%) of them at or after they were judged by the clinician to have developed ARC or AIDS (nearly all confirmed subsequently) and most of the remainder on the basis of low CD4 cell counts. Those in the Imm group spent 81% of the time before ARC or AIDS on zidovudine compared with only 16% for those in the Def group. Despite the large difference in the amount of zidovudine between the two groups and the fact that the number of clinical endpoints (AIDS and death) in Concorde (347) outnumbers the total of those in all other published trials in symptom-free and early symptomatic infection, there was no statistically significant difference in clinical outcome between the two therapeutic policies. The 3-year estimated survival probabilities were 92% (95% CI 90-94%) in Imm and 94% (92-95%) in Def (log-rank p = 0.13), with no significant differences overall or in subgroup analyses by CD4 cell count at baseline. Similarly, there was no significant difference in progression of HIV disease: 3-year progression rates to AIDS or death were 18% in both groups, and to ARC, AIDS, or death were 29% (Imm) and 32% (Def) (p = 0.18), although there was an indication of an early but transient clinical benefit in favour of Imm in progression to ARC, AIDS, or death. However, there was a clear difference in changes in CD4 cell count over time in the two groups.(ABSTRACT TRUNCATED AT 400 WORDS)

Published
2016

16. Myeloma Workshop

Author

Heremans, J. F., Potter, Michael, Fudenberg, H. H., Wang, A-C., Pink, J. R. L., Levin, A. S., Fahey, J. L., Salmon, Sydney E., Seligmann, M., Danon, Françoise, Clauvel, J. P., Virella, G., Wachter, H., Grassmayr, K., Gutter, W., Hausen, A., Sallaberger, G., Gabl, F., Galton, D. A. G., Peto, R., Hobbs, J. R., Bergsagel, D. E., Videbaek, Aage, Osserman, Elliott F., Wiltshaw, E., and Johansson, Bo

Published
1971

17. Germany’s Ocean Greyhounds and the Royal Navy’s First Battle Cruisers: An Historiographical Problem

Author

Seligmann, M

Abstract

Recently some revisionist historians have contested the evidential basis for the argument put forward by their post-revisionist colleagues that the growth of the German mercantile marine, most particularly ships capable of being transformed into armed commerce raiders, was viewed with alarm in the British Admiralty and played a significant part in shaping British naval policy before 1914. Looking in detail at their reasoning, this assessment demonstrates that the rejection of this argument finds basis upon a faulty and incomplete understanding of the documentary record. Moreover, it is driven by a desire to defend the thesis that they have previously articulated that the expansion of German maritime power played a limited role in British defence policy before 1914. However, their objections do not withstand detailed scrutiny. Whatever might have been the British view of the long-term threat posed by Russia and France, Germany’s growing strength, including in merchant shipping, loomed large as a security problem in the decade and one-half before 1914. The wartime activities of German commerce raiders, notably the Kronprinz Wilhelm, suggest that fears of a German commerce war were entirely rational.

Published
2016

19. 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. 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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. 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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. 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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

20. 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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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. 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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

23. 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. E., Mudrikova, T., Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Barth, R. E., Wassenberg, M. W. M., van Elst-Laurijssen, D. H. M., Laan, L. M., van Oers-Hazelzet, E. E. B., Patist, J., Vervoort, S., Nieuwenhuis, H. E., Frauenfelder, R., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Peters, E. J. G., van Agtmael, M. A., Perenboom, R. M., Bomers, M., de Vocht, J., Elsenburg, L. J. M., Pettersson, A. M., Vandenbroucke-Grauls, C. M. J. E., Ang, C. W., Geelen, S. P. M., Wolfs, T. F. W., Bont, L. J., Nauta, N., Bezemer, D. O., Gras, L., van Sighem, A. I., Smit, C., Zaheri, S., Kimmel, V., Tong, Y., Lascaris, B., van den Boogaard, R., Hoekstra, P., de Lang, A., Berkhout, M., Grivell, S., Jansen, A., de Groot, L., van den Akker, M., Bergsma, D., Lodewijk, C., Meijering, R., Peeck, B., Raethke, M., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Tuijn, E., Veenenberg, L., Woudstra, T., Bakker, Y., de Jong, A., Broekhoven, M., Claessen, E., Rademaker, M. J., Munjishvili, L., Kruijne, E., Tuk, B., Bonnet, F., Dupon, M., Chene, G., Breilh, D., Fleury, H., Malvy, D., Mercie, P., Pellegrin, I., Neau, D., Bouchet, S., Gaborieau, V., Lacoste, D., Tchamgoue, S., Thiebaut, R., Lawson-Ayayi, S., Wittkop, L., Bernard, N., Hessamfar, M., Vandenhende, M. A., Dauchy, F. A., Dutronc, H., Longy-Boursier, M., Duffau, P., Roger Schmeltz, J., Pistone, T., Receveur, M. C., Cazanave, C., Ochoa, A., Vareil, M. O., Pellegrin, J. L., Viallard, J. F., Greib, C., Lazaro, E., Lafon, M. E., Reigadas, S., Trimoulet, P., Molimard, M., Titier, K., Moreau, J. F., Haramburu, F., Miremont-Salame, G., Dupont, A., Gerard, Y., Caunegre, L., Andre, K., Bonnal, F., Farbos, S., Gemain, M. C., Ceccaldi, J., De Witte, S., Courtault, C., Monlun, E., Lataste, P., Meraud, J. P., Chossat, I., Blaizeau, M. J., Conte, V., Decoin, M., Delaune, J., Delveaux, S., Diarra, F., D'Ivernois, C., Frosch, A., Hannapier, C., Lenaud, E., Leleux, O., Le Marec, F., Leray, J., Louis, I., Palmer, G., Pougetoux, A., Sicard, X., Touchard, D., Uwamaliya-Nziyumvira, B., Petoumenos, K., Bendall, C., Moore, R., Edwards, S., Watson, K., Roth, N., Nicholson, J., Bloch, M., Franic, T., Baker, D., Vale, R., Carr, A., Cooper, D., Chuah, J., Ngieng, M., Nolan, D., Skett, J., Calvo, G., Mateu, S., Domingo, P., Sambeat, M. A., Gatell, J., Del Cacho, E., Cadafalch, J., Fuster, M., Codina, C., Sirera, G., Vaque, A., Clumeck, N., Necsoi, C., Gennotte, A. F., Gerard, M., Kabeya, K., Konopnicki, D., Libois, A., Martin, C., Payen, M. C., Semaille, P., Van Laethem, Y., Neaton, J., Bartsch, G., Thompson, G., Luskin-Hawk, R., Telzak, E., Abrams, D. I., Cohn, D., Markowitz, N., Arduino, R., Mushatt, D., Friedland, G., Perez, G., Tedaldi, E., Fisher, E., Gordin, F., Crane, L. R., Sampson, J., Baxter, J., Cozzi-Lepri, A., Grint, D., Podlekareva, D., Peters, L., Reekie, J., Fischer, A. H., Losso, M., Elias, C., Vetter, N., Zangerle, R., Karpov, I., Vassilenko, A., Mitsura, V. M., Suetnov, O., Colebunders, R., Vandekerckhove, L., Hadziosmanovic, V., Kostov, K., Begovac, J., Machala, L., Jilich, D., Sedlacek, D., Kronborg, G., Benfield, T., Larsen, M., Gerstoft, J., Katzenstein, T., Hansen, A. -B. E., Skinhoj, P., Pedersen, C., Ostergaard, L., Zilmer, K., Smidt, J., Ristola, M., Katlama, C., Viard, J. -P., Girard, P. -M., Livrozet, J. M., Vanhems, P., Rockstroh, J., Schmidt, R., van Lunzen, J., Degen, O., Stellbrink, H. J., Staszewski, S., Bickel, M., Kosmidis, J., Gargalianos, P., Xylomenos, G., Perdios, J., Panos, G., Filandras, A., Karabatsaki, E., Sambatakou, H., Banhegyi, D., Mulcahy, F., Yust, I., Turner, D., Burke, M., Pollack, S., Hassoun, G., Maayan, S., Vella, S., Esposito, R., Mazeu, I., Mussini, C., Arici, C., Pristera, R., Mazzotta, F., Gabbuti, A., Vullo, V., Lichtner, M., Chirianni, A., Montesarchio, E., Gargiulo, M., Antonucci, G., Testa, A., Narciso, P., Vlassi, C., Zaccarelli, M., Lazzarin, A., Castagna, A., Gianotti, N., Galli, M., Ridolfo, A., Rozentale, B., Zeltina, I., Chaplinskas, S., Hemmer, R., Staub, T., Ormaasen, V., Maeland, A., Bruun, J., Knysz, B., Gasiorowski, J., Horban, A., Bakowska, E., Grzeszczuk, A., Flisiak, R., Boron-Kaczmarska, A., Pynka, M., Parczewski, M., Beniowski, M., Mularska, E., Trocha, H., Jablonowska, E., Malolepsza, E., Wojcik, K., Antunes, F., Doroana, M., Caldeira, L., Mansinho, K., Maltez, F., Duiculescu, D., Rakhmanova, A., Zakharova, N., Buzunova, S., Jevtovic, D., Mokras, M., Stanekova, D., Tomazic, J., Gonzalez-Lahoz, J., Soriano, V., Labarga, P., Medrano, J., Moreno, S., Rodriguez, J. M., Clotet, B., Jou, A., Paredes, R., Tural, C., Puig, J., Bravo, I., Miro, J. M., Gutierrez, M., Mateo, G., Karlsson, A., Flamholc, L., Ledergerber, B., Francioli, P., Cavassini, M., Hirschel, B., Boffi, E., Furrer, H., Battegay, M., Elzi, L., Kravchenko, E., Chentsova, N., Frolov, V., Kutsyna, G., Servitskiy, S., Krasnov, M., Barton, S., Johnson, A. M., Mercey, D., Murphy, M., Weber, J., Scullard, G., Fisher, M., Leen, C., Morfeldt, L., Thulin, G., Akerlund, B., Koppel, K., Hakangard, C., Moroni, M., Angarano, G., Antinori, A., Armignacco, O., Castelli, F., Cauda, Roberto, Di Perri, G., Iardino, R., Ippolito, G., Perno, C. F., von Schloesser, F., Viale, P., Ceccherini-Silberstein, F., Girardi, E., Lo Caputo, S., Puoti, M., Andreoni, M., Ammassari, A., Balotta, C., Bonora, S., Borderi, M., Capobianchi, R., Ceccherini- Silberstein, F., Cingolani, A., Cinque, P., De Luca, A., Di Biagio, A., Gori, A., Guaraldi, G., Lapadula, G., Madeddu, G., Maggiolo, F., Marchetti, G., Marcotullio, S., Monno, L., Quiros Roldan, E., Rusconi, S., Cicconi, P., Formenti, T., Galli, L., Lorenzini, P., Giacometti, A., Costantini, A., Santoro, C., Suardi, C., Vanino, E., Verucchi, G., Minardi, C., Quirino, T., Abeli, C., Manconi, P. E., Piano, P., Vecchiet, J., Falasca, K., Sighinolfi, L., Segala, D., Cassola, G., Viscoli, G., Alessandrini, A., Piscopo, R., Mazzarello, G., Mastroianni, C., Belvisi, V., Bonfanti, P., Caramma, I., Castelli, A. P., Rizzardini, G., Ridolfo, A. L., Piolini, R., Salpietro, S., Carenzi, L., Moioli, M. C., Puzzolante, C., Abrescia, N., Guida, M. G., Onofrio, M., Baldelli, F., Francisci, D., Parruti, G., Ursini, T., Magnani, G., Ursitti, M. A., D'Avino, A., Gallo, L., Nicastri, E., Acinapura, R., Capozzi, M., Libertone, R., Tebano, G., Cattelan, A., Mura, M. S., Caramello, P., Orofino, G. C., Sciandra, M., Pellizzer, G., Manfrin, V., Dollet, K., Caissotti, C., Dellamonica, P., Roger, P. M., Bernard, E., Cua, E., De Salvador-Guillouet, F., Durant, J., Ferrando, S., Dunais, B., Mondain-Miton, V., Perbost, I., Prouvost-Keller, B., Pugliese, P., Naqvi, A., Pillet, S., Risso, K., Aubert, V., Barth, J., Bernasconi, E., Boni, J., Bucher, H. C., Burton-Jeangros, C., Calmy, A., Egger, M., Fehr, J., Fellay, J., Gorgievski, M., Gunthard, H., Haerry, D., Hasse, B., Hirsch, H. 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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

26. Effects of intermittent IL-2 alone or with peri-cycle antiretroviral therapy in early HIV infection: The STALWART study

Author

Tavel, JA, Babiker, A, Carey, C, Fisher, M, Fox, L, Gey, D, Lopardo, GD, Lopez, JC, Markowitz, N, Munroe, D, Paton, N, Ruxrungtham, K, Standridge, B, Wentworth, D, Wyman, N, Aagaard, B, Borup, L, Grarup, J, Jansson, PO, Jensen, K, Lundgren, J, Mollerup, D, Reilev, S, Braimah, N, Darbyshire, J, Horton, J, King, E, Smith, N, Van Hooff, F, Cooper, DA, Courtney-Rodgers, D, Emery, S, Finley, E, Gordin, F, Sánchez, A, Thomas, D, Bebchuk, J, Bollenbeck, P, Denning, E, DuChene, AG, Fosdick, L, Harrison, M, Krum, E, Larson, G, Neaton, JD, Nelson, R, Quan, K, Quan, SFL, Schultz, T, Thompson, G, Collins, S, Haerry, DH, Meulbroek, M, Peavy, D, Rappoport, C, Schwarze, S, Valdez, M, Watson, J, Belloso, WH, Davey, R, Duprez, D, Gatell, JM, Hoy, J, Lifson, A, Pederson, C, Perez, G, Price, R, Prineas, R, Rhame, F, Sampson, JH, Worley, J, Modlin, JF, Beral, V, Chaisson, RE, Fleming, TR, Hill, C, Kim, KM, Murray, BE, Pick, B, Seligmann, M, Weller, I, Luzar, MA, Martinez, A, and Costas, V

Abstract

Background: The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy. Methodology: Participants not on continuous ART with ≥300 CD4+ cells/mm3 were randomized to: no treatment; IL-2 for 5 consecutive days every 8 weeks for 3 cycles; or the same IL-2 regimen with 10 days of ART administered around each IL-2 cycle. CD4 + counts, HIV RNA, and HIV progression events were collected monthly. Principal Findings: A total of 267 participants were randomized. At week 32, the mean CD4+ count was 134 cells greater in the IL-2 alone group (p

Published
2010

34. Zidovudine, didanosine, and zalcitabine in the treatment of HIV infection: meta-analyses of the randomised evidence. HIV Trialists' Collaborative Group

Author

Abrams, D, Allan, D, Antunes, F, Breckenridge, A, Bruun, J, Cameron, W, Carbon, C, Chalmers, I, Chang, H, Chodakewitz, J, Clendenin, N, Clumeck, N, Collier, A, Collins, G, Cooper, E, Cooper, D, Danner, S, D'Aquila, R, DeGruttola, V, DeMasi, R, Dee, L, Deyton, L, Dixon, D, Farthing, C, Feinberg, J, Fischl, M, Flepp, M, Gartland, M, Gatell, J, Gazzard, B, Goebel, F, Gotzsche, P, Gringeri, A, Hall, D, Hamilton, J, Hammer, S, Hartigan, P, Heath-Chiozzi, M, Henry, K, Hill, A, Hirschel, B, Ioannidis, J, Kahn, J, Katlama, C, Katzenstein, D, Killen, J, King, E, de Loes, SK, Kravcik, S, Lange, J, Leavitt, R, Leonard, J, Maeland, A, Mannucci, P, Mathiesen, L, McDade, H, Meibohn, A, Melander, H, Merigan, T, Mulder, J, Myers, M, Neaton, J, Nessling, M, Perrin, L, Pettinelli, C, Phair, J, Phillips, A, Pinching, A, Poppa, A, Power, L, Reiss, P, Richman, D, Rooney, J, Rousseau, F, Rutherford, G, Salgo, M, Sandstrom, E, Saravolatz, L, Savidge, G, Schnittman, S, Schooley, R, Seligmann, M, Simberkoff, M, Skowron, G, Slade, P, Smith, D, Smith, RP, Soriano, V, Stanley, K, Stingl, G, Stoffels, P, Struthers, L, Tierney, C, Thompson, M, Van der Broeck, R, Van Leeuven, R, Van Weverling, G, Veenstra, J, Vella, S, Volberding, P, Weber, J, Winslow, D, Yeni, P, Yeo, J, Dormont, J, Sande, M, Weller, I, Babiker, A, Collins, R, Darbyshire, J, Duncan, W, Foulkes, M, Hughes, M, Peto, R, Peto, T, Walker, S, and Grp, HIVTC

Abstract

BACKGROUND: To assess the effects of zidovudine, didanosine, and zalcitabine on HIV disease progression and survival, we undertook meta-analyses of individual patient data and tabular data from all randomised trials that compared these agents. METHODS: Individual patient data were available for 7722 participants without AIDS in the nine randomised trials of immediate versus deferred zidovudine, and 7700 participants with or without AIDS in the six trials comparing zidovudine plus didanosine, zidovudine plus zalcitabine, or zidovudine alone. The main outcomes were mortality and disease progression (new AIDS-defining event or death before any such event). FINDINGS: In the comparison of immediate versus deferred zidovudine, during a median follow-up of 50 months, 1908 individuals progressed, of whom 1351 died. In the deferred group, 61% started antiretroviral therapy (median time to therapy 28 months, which was zidovudine monotherapy in 94%). During the first year of follow-up, immediate zidovudine halved the rate of disease progression (p

Published
1999

36. Treatment of mixed cryoglobulinemia with recombinant interferon alpha and adjuvant therapies. A prospective study on 20 patients

Author

Cohen, P., Nguyen, Qt, Deny, P., Ferriere, F., Dominique ROULOT, Lortholary, O., Jarrousse, B., Danon, F., Barrier, Jh, Ceccaldi, J., Constans, J., Crickx, B., Fiessinger, Jn, Hachulla, E., Jaccard, A., Seligmann, M., Kazatchkine, M., Laroche, L., Subra, Jf, Turlure, P., and Guillevin, L.

Subjects
Aged, 80 and over, Male, Plasma Exchange, Injections, Subcutaneous, Middle Aged, Antiviral Agents, Hepatitis C, Recombinant Proteins, Cryoglobulinemia, Adrenal Cortex Hormones, Chemotherapy, Adjuvant, Recurrence, Interferon Type I, Humans, Female, Prospective Studies, Aged
Abstract

In order to evaluate the efficacy of interferon alpha (IFNa) in mixed cryoglobulinemia (MC), a prospective multicenter clinical trial was conduced in April 1992. It consisted of treating 20 clinically symptomatic MC patients with IFNa for 26 weeks. Hepatitis C virus (HCV) infection was detected in 16 patients. A complete or partial clinical remission was obtained in 12 patients (60%). Eleven of these 12 responders (91.6%) experienced a clinical relapse less than 12 months after the end of therapy. Side effects were noted in 10 patients (50%). It was concluded that subcutaneously administered IFNa does not provide long-term remission.

Published
1996

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