Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study.


Bruyand, M; Ryom, L; Shepherd, L; Fatkenheuer, G; Grulich, A; Reiss, P; de Wit, S; D Arminio Monforte, A; Furrer, H; Pradier, C; Lundgren, J; Sabin, C; D:A:D study group, ; , COLLABORATORS; Powderly, B; Shortman, N; Moecklinghoff, C; Reilly, G; Franquet, X; Ryom, L; Sabin, CA; Kamara, D; Smith, C; Phillips, A; Mocroft, A; Tverland, J; Mansfeld, M; Nielsen, J; Raben, D; Lundgren, JD; 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; Ryom, L; Mocroft, A; Kirk, O; Reiss, P; Ross, M; Fux, CA; Morlat, P; Moranne, O; Kesselring, AM; Kamara, DA; Smith, C; Lundgren, JD; Smith, C; Ryom, L; Phillips, A; Weber, R; Morlat, P; Pradier, C; Reiss, P; Friis-Møller, N; Kowalska, J; Lundgren, JD; Sabin, C; Law, M; d'Arminio Monforte, A; Dabis, F; Bruyand, M; Reiss, P; Smith, C; Kamara, DA; Bower, M; Fätkenheuer, G; Donald, A; Grulich, A; Ryom, L; Lundgren, JD; Reiss, P; Zaheri, S; Hillebregt, M; Gras, L; Prins, JM; Kuijpers, TW; Scherpbier, HJ; van der Meer, JT; Wit, FW; Godfried, MH; Reiss, P; van der Poll, T; Nellen, FJ; Lange, JM; Geerlings, SE; van Vugt, M; Pajkrt, D; Bos, JC; van der Valk, M; Grijsen, ML; Wiersinga, WJ; Goorhuis, A; Hovius, JW; Lowe, S; Oude Lashof, A; Posthouwer, D; Pronk, MJ; Ammerlaan, HS; van der Ende, ME; de Vries-Sluijs, TE; Schurink, CA; Nouwen, JL; Verbon, A; Rijnders, BJ; van Gorp, EC; van der Feltz, M; Driessen, GJ; van Rossum, AM; Branger, J; Schippers, EF; van Nieuwkoop, C; van Elzakker, EP; Groeneveld, PH; Bouwhuis, JW; Soetekouw, R; ten Kate, RW; Kroon, FP; van Dissel, JT; Arend, SM; de Boer, MG; Jolink, H; ter Vollaard, HJ; Bauer, MP; den Hollander, JG; Pogany, K; van Twillert, G; Kortmann, W; Cohen Stuart, JW; Diederen, BM; Leyten, EM; Gelinck, LB; Kootstra, GJ; Delsing, CE; Brinkman, K; Blok, WL; Frissen, PH; Schouten, WE; van den Berk, GE; van Kasteren, ME; Brouwer, AE; Veenstra, J; Lettinga, KD; Mulder, JW; Vrouenraets, SM; Lauw, FN; van Eeden, A; Verhagen, DW; Sprenger, HG; Doedens, R; Scholvinck, EH; van Assen, S; Bierman, WF; Koopmans, PP; Keuter, M; van der Ven, AJ; ter Hofstede, HJ; Dofferhoff, AS; Warris, A; van Crevel, R; Hoepelman, AI; Mudrikova, T; Schneider, MM; Ellerbroek, PM; Oosterheert, JJ; Arends, JE; Wassenberg, MW; Barth, RE; van Agtmael, MA; Perenboom, RM; Claessen, FA; Bomers, M; Peters, EJ; Geelen, SP; Wolfs, TF; Bont, LJ; Richter, C; van der Berg, JP; Gisolf, EH; van den Berge, M; Stegeman, A; van Vonderen, MG; van Houte, DP; Weijer, S; el Moussaoui, R; Winkel, C; Muskiet, F; Durand, ; Voigt, R; Dabis, F; Bonnet, F; Breilh, D; Dabis, F; Dupon, M; Chêne, G; Fleury, H; Malvy, D; Mercié, P; Pellegrin, I; Morlat, P; Neau, D; Pellegrin, JL; Thiébaut, R; Bouchet, S; Gaborieau, V; Lacoste, D; Tchamgoué, S; Chêne, G; Dabis, F; Thiébaut, R; Bruyand, M; Lawson-Ayayi, S; Wittkop, L; Morlat, P; Bonnet, F; Bernard, N; Hessamfar, M; Lacoste, D; Vandenhende, MA; Dupon, M; Dauchy, FA; Dutronc, H; Longy-Boursier, M; Mercié, P; Duffau, P; Schmeltz, JR; Malvy, D; Pistone, T; Receveur, MC; Neau, D; Cazanave, C; Ochoa, A; Vareil, MO; Pellegrin, JL; Viallard, JF; Greib, C; Lazaro, E; Fleury, H; Lafon, ME; Reigadas, S; Trimoulet, P; Breilh, D; Molimard, M; Bouchet, S; Titier, K; Moreau, JF; Pellegrin, I; Haramburu, F; Miremont-Salamé, G; Dupont, A; Gerard, Y; Caunègre, L; André, K; Bonnal, F; Farbos, S; Gemain, MC; Ceccaldi, J; Tchamgoué, S; De Witte, S; Courtault, C; Monlun, E; Gaborieau, V; Lataste, P; Meraud, JP; Chossat, I; Blaizeau, MJ; Bruyand, M; Conte, V; Decoin, M; Delaune, J; Delveaux, S; Diarra, F; D'Ivernois, C; Frosch, A; Geffard, S; Hanappier, C; Lawson-Ayayi, S; Lenaud, E; Leleux, U; Le Marec, F; Leray, J; Louis, I; Palmer, G; Pougetoux, A; Sicard, X; Touchard, D; Uwamaliya-Nziyumvira, B; Law, M; Petoumenos, K; McManus, H; Wright, S; Bendall, C; Moore, R; Edwards, S; Hoy, J; Watson, K; Roth, N; Nicholson, J; Bloch, M; Franic, T; Baker, D; Vale, R; Carr, A; Cooper, D; Chuah, J; Ngieng, A; Nolan, D; Skett, J; Calvo, G; Torres, F; Mateu, S; Domingo, P; Sambeat, MA; Gatell, J; Del Cacho, E; Cadafalch, J; Fuster, M; Codina, C; Sirera, G; Vaqué, A; De Wit, S; Clumeck, N; Delforge, M; Necsoi, C; Clumeck, N; De Wit, S; Gennotte, AF; Gerard, M; Kabeya, K; Konopnicki, D; Libois, A; Martin, C; Payen, MC; Semaille, P; Van Laethem, Y; Neaton, J; Bartsch, G; El-Sadr, WM; Krum, E; Thompson, G; Wentworth, D; Luskin-Hawk, R; Telzak, E; El-Sadr, WM; Abrams, DI; Cohn, D; Markowitz, N; Arduino, R; Mushatt, D; Friedland, G; Perez, G; Tedaldi, E; Fisher, E; Gordin, F; Crane, LR; Sampson, J; Baxter, J; Kirk, O; Mocroft, A; Cozzi-Lepri, A; Grint, D; Podlekareva, D; Kjær, J; Peters, L; Reekie, J; Kowalska, J; Tverland, J; Fischer, AH; Nielsen, J; Losso, M; Elias, C; Vetter, N; Zangerle, R; Karpov, I; Vassilenko, A; Mitsura, VM; Suetnov, O; Clumeck, N; De Wit, S; Delforge, M; Colebunders, R; Vandekerckhove, L; Hadziosmanovic, V; Kostov, K; Begovac, J; Machala, L; Sedlacek, D; Nielsen, J; Kronborg, G; Benfield, T; Larsen, M; Gerstoft, J; Katzenstein, T; Hansen, AB; Skinhøj, P; Pedersen, C; Ostergaard, L; Zilmer, K; Smidt, J; Ristola, M; Katlama, C; Viard, JP; Girard, PM; Livrozet, JM; Vanhems, P; Pradier, C; Dabis, F; Neau, D; Rockstroh, J; Schmidt, R; van Lunzen, J; Degen, O; Stellbrink, HJ; Staszewski, S; Bickel, M; Fätkenheuer, G; 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; d'Arminio Monforte, A; Rozentale, B; Zeltina, I; Chaplinskas, S; Hemmer, R; Staub, T; Reiss, P; 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; Mokráš, M; Tomazic, J; González-Lahoz, J; Soriano, V; Labarga, P; Medrano, J; Moreno, S; Rodriguez, JM; Clotet, B; Jou, A; Paredes, R; Tural, C; Puig, J; Bravo, I; Gatell, JM; Miró, JM; Domingo, P; Gutierrez, M; Mateo, G; Sambeat, MA; Karlsson, A; Flamholc, L; Ledergerber, B; Weber, R; 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, AM; Mercey, D; Phillips, A; Johnson, MA; Mocroft, A; Murphy, M; Weber, J; Scullard, G; Fisher, M; Leen, C; Morfeldt, L; Thulin, G; Sundström, A; Åkerlund, B; Koppel, K; Karlsson, A; Flamholc, L; Håkangård, C; Moroni, M; Angarano, G; Antinori, A; Armignacco, O; d'Arminio Monforte, A; Castelli, F; Cauda, R; Di Perri, G; Galli, M; Iardino, R; Ippolito, G; Lazzarin, A; Perno, CF; von Schloesser, F; d'Arminio Monforte, A; Antinori, A; Castagna, A; Ceccherini-Silberstein, F; Cozzi-Lepri, A; Girardi, E; Lo Caputo, S; Mussini, C; Andreoni, M; Ammassari, A; Antinori, A; d'Arminio Monforte, A; Balotta, C; Bonfanti, P; Bonora, S; Borderi, M; Capobianchi, R; Castagna, A; Ceccherini-Silberstein, F; Cingolani, A; Cinque, P; Cozzi-Lepri, A; De Luca, A; Di Biagio, A; Girardi, E; Gianotti, N; Gori, A; Guaraldi, G; Lapadula, G; Lichtner, M; Lo Caputo, S; Madeddu, G; Maggiolo, F; Marchetti, G; Marcotullio, S; Monno, L; Mussini, C; Puoti, M; Quiros Roldan, E; Cozzi-Lepri, A; Cicconi, P; Fanti, I; Formenti, T; Galli, L; Lorenzini, P; Giacometti, A; Costantini, A; Angarano, G; Monno, L; Santoro, C; Maggiolo, F; Suardi, C; Viale, P; Vanino, E; Verucchi, G; Castelli, F; Quiros Roldan, E; Minardi, C; Quirino, T; Abeli, C; Manconi, PE; Piano, P; Vecchiet, J; Falasca, K; Sighinolfi, L; Segala, D; Mazzotta, F; Lo Caputo, S; Cassola, G; Viscoli, G; Alessandrini, A; Piscopo, R; Mazzarello, G; Mastroianni, C; Belvisi, V; Bonfanti, P; Caramma, I; Castelli, AP; Galli, M; Lazzarin, A; Rizzardini, G; Puoti, M; d'Arminio Monforte, A; Ridolfo, AL; Piolini, R; Castagna, A; Salpietro, S; Carenzi, L; Moioli, MC; Cicconi, P; Marchetti, G; Mussini, C; Puzzolante, C; Gori, A; Lapadula, G; Abrescia, N; Chirianni, A; Guida, MG; Onofrio, M; Baldelli, F; Francisci, D; Parruti, G; Ursini, T; Magnani, G; Ursitti, MA; Cauda, R; Andreoni, M; Antinori, A; Vullo, V; Cingolani, A; d'Avino, A; Ammassari, A; Gallo, L; Nicastri, E; Acinapura, R; Capozzi, M; Libertone, R; Tebano, G; Cattelan, A; Mura, MS; Madeddu, G; Caramello, P; Di Perri, G; Orofino, GC; Bonora, S; Sciandra, M; Pellizzer, G; Manfrin, V; Pradier, C; Fontas, E; Caissotti, C; Dellamonica, P; Bernard, E; Cua, E; De Salvador-Guillouet, F; Durant, J; Ferrando, S; Mondain-Miton, V; Naqvi, A; Perbost, I; Prouvost-Keller, B; Pillet, S; Pugliese, P; Rahelinirina, V; Roger, PM; Dollet, K; Aubert, V; Barth, J; Battegay, M; Bernasconi, E; Böni, J; Bucher, HC; Burton-Jeangros, C; Calmy, A; Cavassini, M; Egger, M; Elzi, L; Fehr, J; Fellay, J; Furrer, H; Fux, CA; Gorgievski, M; Günthard, H; Haerry, D; Hasse, B; Hirsch, HH; Hösli, I; Kahlert, C; Kaiser, L; Keiser, O; Klimkait, T; Kovari, H; Ledergerber, B; Martinetti, G; Martinez de Tejada, B; Metzner, K; Müller, N; Nadal, D; Pantaleo, G; Rauch, A; Regenass, A; Rickenbach, M; Rudin, C; Schmid, P; Schultze, D; Schöni-Affolter, F; Schüpbach, J; Speck, R; Taffé, P; Tarr, P; Telenti, A; Trkola, A; Vernazza, P; Weber, R; Yerly, S; (2015) Cancer risk and use of protease inhibitor or nonnucleoside reverse transcriptase inhibitor-based combination antiretroviral therapy: the D: A: D study. Journal of acquired immune deficiency syndromes (1999), 68 (5). pp. 568-77. ISSN 1525-4135 DOI: https://doi.org/10.1097/QAI.0000000000000523

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Abstract

The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear. Participants were followed from the latest of D:A:D study entry or January 1, 2004, until the earliest of a first cancer diagnosis, February 1, 2012, death, or 6 months after the last visit. Multivariable Poisson regression models assessed associations between cumulative (per year) use of either any cART or PI/NNRTI, and the incidence of any cancer, non-AIDS-defining cancers (NADC), AIDS-defining cancers (ADC), and the most frequently occurring ADC (Kaposi sarcoma, non-Hodgkin lymphoma) and NADC (lung, invasive anal, head/neck cancers, and Hodgkin lymphoma). A total of 41,762 persons contributed 241,556 person-years (PY). A total of 1832 cancers were diagnosed [incidence rate: 0.76/100 PY (95% confidence interval: 0.72 to 0.79)], 718 ADC [0.30/100 PY (0.28-0.32)], and 1114 NADC [0.46/100 PY (0.43-0.49)]. Longer exposure to cART was associated with a lower ADC risk [adjusted rate ratio: 0.88/year (0.85-0.92)] but a higher NADC risk [1.02/year (1.00-1.03)]. Both PI and NNRTI use were associated with a lower ADC risk [PI: 0.96/year (0.92-1.00); NNRTI: 0.86/year (0.81-0.91)]. PI use was associated with a higher NADC risk [1.03/year (1.01-1.05)]. Although this was largely driven by an association with anal cancer [1.08/year (1.04-1.13)], the association remained after excluding anal cancers from the end point [1.02/year (1.01-1.04)]. No association was seen between NNRTI use and NADC [1.00/year (0.98-1.02)]. Cumulative use of PIs may be associated with a higher risk of anal cancer and possibly other NADC. Further investigation of biological mechanisms is warranted.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
PubMed ID: 25763785
URI: http://researchonline.lshtm.ac.uk/id/eprint/4646608

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