Non-AIDS defining cancers in the D:A:D Study - time trends and predictors of survival: A cohort study

Signe W. Worm, Mark Bower, Peter Reiss, Fabrice Bonnet, Matthew Law, Gerd Fätkenheuer, Antonella d'Arminio Monforte, Donald I. Abrams, Andrew Grulich, Eric Fontas, Ole Kirk, Hansjakob Furrer, Stephane D. Wit, Andrew Phillips, Jens D. Lundgren, Caroline A. Sabin, D. Butcher, M. Delforge, I. Fanti, E. FontasX. Franquet, S. Geffard, L. Gras, J. Helweg-Larsen, M. Hillebregt, D. Kamara, J. Kjær, E. Krum, J. D. Lundgren, H. McManus, P. Meidahl, A. Mocroft, J. Nielsen, A. Phillips, W. Powderl, M. Rickenbach, R. Rode, L. Ryom, C. A. Sabin, R. Salbøl Brandt, J. Schmidt Iversen, N. Shortman, A. Sjøl, C. Smith, F. Torres, J. Tverland, S. Wright, S. Zaheri, F. de Wolf, J. Smidt, M. Ristola, C. Katlama, J. P. Viard, P. M. Girard, J. M. Livrozet, P. Vanhems, C. Pradier, F. Dabis, D. Neau, J. Rockstroh, R. Schmidt, O. Degen, J. van Lunzen, H. J. Stellbrink, S. Staszewski, J. Bogner, G. Fätkenheuer, P. Gargalianos, J. Kosmidis, J. Perdios, G. Xylomenos, A. Filandras, E. Karabatsaki, G. Panos, H. Sambatakou, D. Banhegyi, F. Mulcahy, M. Burke, D. Turner, I. Yust, G. Hassoun, S. Pollack, S. Maayan, S. Vella, R. Esposito, I. Mazeu, C. Mussini, C. Arici, R. Pristera, A. Gabbuti, F. Mazzotta, M. Lichtner, V. Vullo, K. Boer, S. E. Geerlings, M. H. Godfried, T. W. Kuijpers, J. M A Lange, F. J B Nellen, D. Pajkrt, J. M. Prins, P. Reiss, H. J. Scherpbier, S. M E Vrouenraets, F. W M N Wit, M. van Vugt, J. T M van der Meer, T. van der Poll, M. van der Valk, A. Chirianni, M. Gargiulo, E. Montesarchio, G. Antonucci, P. Narciso, A. Testa, C. Vlassi, M. Zaccarelli, A. Castagna, N. Gianotti, A. Lazzarin, M. Galli, A. Ridolfo, A. d'Arminio Monforte, B. Rozentale, I. Zeltina, S. Chaplinskas, R. Hemmer, T. Staub, P. Reiss, J. Bruun, A. Maeland, V. Ormaasen, S. Lowe, A. Oude Lashof, G. Schreij, J. Gasiorowski, B. Knysz, E. Bakowska, A. Horban, R. Flisiak, A. Grzeszczuk, A. Boron-Kaczmarska, M. Parczewski, M. Pynka, M. Beniowski, E. Mularska, H. Trocha, E. Jablonowska, E. Malolepsza, K. Wojcik, F. Antunes, L. Caldeira, M. Doroana, K. Mansinho, F. Maltez, B. Bravenboer, M. J H Pronk, D. Duiculescu, A. Rakhmanova, N. Zakharova, S. Buzunova, D. Jevtovic, M. Mokráš, D. Staneková, J. Tomazic, J. González-Lahoz, P. Labarga, J. Medrano, V. Soriano, S. Moreno, J. M. Rodriguez, I. Bravo, B. Clotet, A. Jou, R. Paredes, J. Puig, C. Tural, L. B S Gelinck, J. L. Nouwen, B. J A Rijnders, C. A M Schurink, L. Slobbe, A. Verbon, T. E M S de Vries-Sluijs, M. E. van der Ende, M. van der Feltz, J. M. Gatell, J. M. Miró, P. Domingo, M. Gutierrez, G. Mateo, M. A. Sambeat, A. Karlsson, L. Flamholc, B. Ledergerber, R. Weber, M. Cavassini, P. Francioli, E. Boffi, B. Hirschel, H. Furrer, M. Battegay, L. Elzi, N. Chentsova, E. Kravchenko, G. J A Driessen, N. G. Hartwig, V. Frolov, G. Kutsyna, S. Servitskiy, M. Krasnov, S. Barton, A. M. Johnson, D. Mercey, M. A. Johnson, A. Mocroft, A. Phillips, M. Murphy, G. Scullard, J. Weber, M. Fisher, C. Leen, J. Branger, B. Åkerlund, L. Morfeldt, A. Sundström., G. Thulin, A. Karlsson, K. Koppel, L. Flamholc, C. Ho̊kangård, G. Angarano, A. Antinori, O. Armignacco, F. Castelli, R. Cauda, G. Di Perri, M. Galli, R. Iardino, G. Ippolito, A. Lazzarin, M. Moroni, C. F. Perno, P. L. Viale, F. Von Schlosser, A. Ammassari, M. Andreoni, A. Antinori, C. Balotta, P. Bonfanti, S. Bonora, M. Borderi, M. R. Capobianchi, A. Castagna, F. Ceccherini-Silberstein, P. Cinque, A. Cozzi-Lepri, A. De Luca, M. Gargiulo, C. Gervasoni, E. Girardi, A. Gori, G. Guaraldi, M. Lichtner, S. Lo Caputo, G. Madeddu, F. Maggiolo, G. Marchetti, S. Marcotullio, L. Monno, R. Murri, C. Mussini, M. Puoti, C. Torti, A. d'Arminio Monforte, P. Cicconi, A. Cozzi-Lepri, I. Fanti, T. Formenti, L. Galli, P. Lorenzini, A. Costantini, A. Giacometti, A. Riva, G. Angarano, C. Carrisa, L. Monno, G. Lazzari, F. Maggiolo, M. Borderi, G. Verucchi, P. L. Viale, R. H. Kauffmann, E. F. Schippers, F. Castelli, C. Minardi, C. Torti, C. Abeli, T. Quirino, P. E. Manconi, P. Piano, K. Falasca, J. Vecchiet, D. Segala, L. Sighinolfi, S. Lo Caputo, F. Mazzotta, A. Alessandrini, G. Cassola, G. Mazzarello, R. Piscopo, G. Viscoli, V. Belvisi, C. Mastroianni, P. Bonfanti, I. Caramma, P. Castelli, A. Chiodera, M. A. Alleman, J. W. Bouwhuis, P. H P Groeneveld, A. Bigoloni, L. Carenzi, A. Castagna, P. Cicconi, T. Formenti, A. Galli, M. Galli, A. Lazzarin, M. C. Moioli, R. Piolini, M. Puoti, A. L. Ridolfo, G. Rizzardini, R. Rossotti, S. Salpietro, V. Spagnuolo, P. Zucchi, A. d'Arminio Monforte, L. Bisio, C. Mussini, A. Gori, G. Lapadula, N. Abrescia, A. Chirianni, M. Gargiulo, M. G. Guida, F. Baldelli, B. Belfiori, G. Parruti, T. Ursini, G. Magnani, M. A. Ursitti, R. Acinapura, M. Andreoni, A. Antinori, M. Capozzi, R. Cauda, A. De Luca, L. Gallo, R. Libertone, M. Lichtner, E. Nicastro, G. Tebano, V. Tozzi, V. Vullo, M. Zaccarelli, A. d'Avino, G. Madeddu, M. S. Mura, P. Caramello, G. Di Perri, G. C. Orofino, M. Sciandra, R. Soetekouw, R. W. ten Kate, V. Manfrin, G. Pellizzer, E. Bernard, C. Caissotti, E. Cua, F. De Salvador-Guillouet, P. Dellamonica, K. Dollet, J. Durant, S. Ferrando, E. Fontas, V. Mondain-Miton, A. Naqvi, I. Perbost, S. Pillet, C. Pradier, B. Prouvost-Keller, P. Pugliese, V. Rahelinirina, P. M. Roger, J. Barth, M. Battegay, E. Bernasconi, J. Böni, H. C. Bucher, C. Burton-Jeangros, A. Calmy, M. Cavassini, C. Cellerai, R. Dubs, M. Egger, L. Elzi, J. Fehr, M. Flepp, P. Francioli, H. Furrer, C. A. Fux, M. Gorgievski, H. Günthard, B. Hasse, H. H. Hirsch, B. Hirschel, I. Hösli, C. Kahlert, L. Kaiser, O. Keiser, C. Kind, T. Klimkait, H. Kovari, B. Ledergerber, G. Martinetti, B. Martinez de Tejada, N. Müller, D. Nadal, G. Pantaleo, A. Rauch, S. Regenass, M. Rickenbach, C. Rudin, P. Schmid, F. Schöni-Affolter, J. Schüpbach, D. Schultze, R. Speck, P. Taffé, A. Telenti, A. Trkola, P. Vernazza, R. Weber, S. Yerly, V. von Wyl, S. M. Arend, H. Jolink, F. P. Kroon, M. G J de Boer, J. T. van Dissel, C. van Nieuwkoop, P. J. van den Broek, K. Pogany, J. G. den Hollander, W. Kortmann, G. van Twillert, E. M S Leyten, R. Vriesendorp, G. J. Kootstra, C. H H ten Napel, W. L. Blok, K. Brinkman, P. H J Frissen, W. E M Schouten, G. E L van den Berk, A. E. Brouwer, J. R. Juttmann, M. E E van Kasteren, K. D. Lettinga, J. Veenstra, J. W. Mulder, P. M. Smit, S. Weijer, E. C M van Gorp, D. W M Verhagen, A. van Eeden, R. Doedens, E. H. Scholvinck, H. G. Sprenger, C. J. Stek, S. van Assen, A. M. Brouwer, A. S M Dofferhoff, M. Keuter, P. P. Koopmans, R. de Groot, H. J M ter Hofstede, M. van der Flier, A. J A M van der Ven, J. E. Arends, P. M. Ellerbroek, A. I M Hoepelman, C. A J J Jaspers, L. J. Maarschalk-Ellerbroek, T. Mudrikova, J. J. Oosterheert, E. J G Peters, M. M E Schneider, M. W M Wassenberg, J. C H van der Hilst, W. F W Bierman, F. A P Claessen, S. A. Danner, R. M. Perenboom, E. A. bij de Vaate, E. V. de Jong, J. de Vocht, M. A. van Agtmael, S. P M Geelen, T. F W Wolfs, E. H. Gisolf, J. P. Richter, C. van der Berg, A. Stegeman, M. van den Berge, M. B. Polée, D. P F van Houte, M. G A van Vonderen, A. J. Duits, C. Winkel, F. Dabis, F. Bonnet, G. Chêne, F. Dabis, M. Dupon, H. Fleury, D. Lacoste, D. Malvy, P. Mercié, P. Morlat, D. Neau, I. Pellegrin, J. L. Pellegrin, R. Thiébaut, K. Titier, M. Bruyand, G. Chêne, F. Dabis, S. Lawson-Ayayi, R. Thiébaut, L. Wittkop, N. Bernard, F. Bonnal, F. Bonnet, L. Caunègre, C. Cazanave, J. Ceccaldi, D. Chambon, I. Chossat, K. Courtaud, F. A. Dauchy, S. De Witte, P. Duffau, M. Dupon, A. Dupont, H. Dutronc, S. Farbos, V. Gaboriau, M. C. Gemain, Y. Gerard, C. Greib, M. Hessamfar, D. Lacoste, S. Lafarie-Castet, P. Lataste, E. Lazaro, M. Longy-Boursier, D. Malvy, J. P. Meraud, P. Mercié, E. Monlun, P. Morlat, D. Neau, A. Ochoa, J. L. Pellegrin, T. Pistone, J. M. Ragnaud, M. C. Receveur, J. Roger-Schmeltz, S. Tchamgoué, P. Thibaut, M. A. Vandenhende, J. F. Viallard, J. F. Moreau, I. Pellegrin., H. Fleury, M. E. Lafon, B. Masquelier, P. Trimoulet, D. Breilh, K. Titier, F. Haramburu, G. Miremont-Salamé, M. J. Blaizeau, C. D'Ivernois, M. Decoin, J. Delaune, S. Delveaux, C. Hanappier, O. Leleux, X. Sicard, B. Uwamaliya-Nziyumvira, S. Geffard, J. Leray, G. Palmer, D. Touchard, D. Baker, C. Bendall, M. Bloch, A. Carr, D. Cooper, T. Franic, M. Law, H. McManus, K. Petoumenos, R. Vale, S. Wright, S. Edwards, J. Hoy, R. Moore, J. Nicholson, N. Roth, K. Watson, J. Chuah, M. Ngieng, D. Nolan, J. Skett, J. Cadafalch, G. Calvo, C. Codina, E. Del Cacho, P. Domingo, M. Fuster, J. Gatell, S. Mateu, M. A. Sambeat, G. Sirera, F. Torres, A. Vaqué, N. Clumeck, S. De Wit, M. Delforge, A. F. Gennotte, M. Gerard, K. Kabeya, D. Konopnicki, A. Libois, C. Martin, C. Necsoi, M. C. Payen, P. Semaille, Y. Van Laethem, G. Bartsch, W. M. El-Sadr, E. Krum, J. Neaton, G. Thompson, D. Wentworth, R. Luskin-Hawk, E. Telzak, W. M. El-Sadr, D. I. Abrams, D. Cohn, N. Markowitz, R. Arduino, D. Mushatt, G. Friedland, G. Perez, E. Tedaldi, E. Fisher, F. Gordin, L. R. Crane, J. Sampson, J. Baxter, A. Cozzi-Lepri, A. H. Fischer, D. Grint, O. Kirk, J. Kjaer, J. Kowalska, J. Lundgren, A. Mocroft, J. Nielsen, L. Peters, D. Podlekareva, J. Reekie, J. Tverland, C. Elias, M. Losso, N. Vetter, R. Zangerle, N. Vetter, R. Zangerle, I. Karpov, A. Vassilenko, V. M. Mitsura, O. Suetnov, N. Clumeck, S. De Wit, M. Delforge, R. Colebunders, L. Vandekerckhove, V. Hadziosmanovic, K. Kostov, J. Begovac, D. Jilich, L. Machala, D. Sedlacek, T. Benfield, G. Kronborg, M. Larsen, J. Nielsen, J. Gerstoft, A. B E Hansen, T. Katzenstein, P. Skinhøj, C. Pedersen, L. Ostergaard, K. Zilmer

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

Abstract

Background: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.Methods: Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.Results: Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.Conclusions: The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC.

Original languageEnglish (US)
Article number471
JournalBMC infectious diseases
Volume13
Issue number1
DOIs
StatePublished - Oct 9 2013

Bibliographical note

Funding Information:
This work was supported by the Highly Active Antiretroviral Therapy Oversight Committee (HAART-OC), a collaborative committee with representation from academic institutions, the European Agency for the Evaluation of Medicinal Products, the United States Food and Drug Administration, the patient community, and all pharmaceutical companies with licensed anti-HIV drugs in the European Union: Abbott Laboratories, Boehringer Ingelheim Pharmaceuticals Inc., Bristol-Myers Squibb, Gilead Sciences Inc., Viiv Healthcare, Merck & Co Inc., Pfizer Inc, F. Hoffman-LaRoche Ltd and Janssen Pharmaceuticals. Supported by a grant [grant number CURE/97-46486] from the Health Insurance Fund Council, Amstelveen, the Netherlands, to the AIDS Therapy Evaluation Project Netherlands (ATHENA); by a grant from the Agence Nationale de Recherches sur le SIDA [grant number Action Coordonnée no.7, Cohortes], to the Aquitaine Cohort; The Australian HIV Observational Database (AHOD) is funded as part of the Asia Pacific HIV Observational Database, a program of The Foundation for AIDS Research, amfAR, and is supported in part by a grant from the U.S. National Institutes of Health’s National Institute of Allergy and Infectious Diseases (NIAID) [grant number U01-AI069907] and by unconditional grants from Merck Sharp & Dohme; Gilead Sciences; Bristol-Myers Squibb; Boehringer Ingelheim Pharmaceuticals Inc.; Roche; Pfizer; GlaxoSmithKline; Janssen Pharmaceuticals. The Kirby Institute is funded by The Australian Government Department of Health and Ageing, and is affiliated with the Faculty of Medicine, The University of New South Wales. By grants from the Fondo de Investigación Sanitaria [grant number FIS 99/0887] and Fundación para la Investigación y la Prevención del SIDA en Espanã [grant number FIPSE 3171/00], to the Barcelona Antiretroviral Surveillance Study (BASS); by the National Institute of Allergy and Infectious Diseases, National Institutes of Health [grants number 5U01AI042170-10 , 5U01AI046362-03], to the Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA); by grants from the BIOMED 1 [grant number CT94-1637] and BIOMED 2 [grant number CT97-2713] programs and the fifth framework program [grant number QLK2-2000-00773] of the European Commission and grants from Bristol-Myers Squibb, GlaxoSmithKline, Boehringer Ingelheim Pharmaceuticals Inc., and Roche, to the EuroSIDA study; by unrestricted educational grants of Abbott Laboratories, Bristol-Myers Squibb, Gilead Sciences Inc., GlaxoSmithKline, Pfizer Inc., Janssen Pharmaceuticals to the Italian Cohort Naive to Antiretrovirals (The ICONA Foundation); and by a grant from the Swiss National Science Foundation, to the Swiss HIV Cohort Study (SHCS). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of any of the institutions mentioned above.

Funding Information:
SWW was supported by the Danish Research Council. Grant number 09–070575. Part of the data included in this manuscript has been presented as an oral presentation at EACS, Belgrade, Serbia October 2011.

Keywords

  • HIV
  • Incidence
  • Non-AIDS defining cancers
  • Prognosis
  • Trends

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