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J Acquir Immune Defic Syndr. 2015 Apr 15;68(5):568-77. doi: 10.1097/QAI.0000000000000523.

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

Collaborators (753)

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.

Abstract

BACKGROUND:

The association between combination antiretroviral therapy (cART) and cancer risk, especially regimens containing protease inhibitors (PIs) or nonnucleoside reverse transcriptase inhibitors (NNRTIs), is unclear.

METHODS:

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).

RESULTS:

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)].

CONCLUSIONS:

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.

PMID:
25763785
DOI:
10.1097/QAI.0000000000000523
[Indexed for MEDLINE]

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