Background: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. Objective: To estimate the long-term risk difference for cancer with the immediate ART strategy. Design: Multinational prospective cohort study. Setting: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. Participants: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). Measurements: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts < 350 and < 500 × 109 cells/L) ART initiation strategies. Results: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. Limitation: Potential residual confounding due to observational study design. Conclusion: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. Primary Funding Source: Highly Active Antiretroviral Therapy Oversight Committee.

Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy: A multinational prospective cohort study / F. Chammartin, S. Lodi, R. Logan, L. Ryom, A. Mocroft, O. Kirk, A. D'Arminio Monforte, P. Reiss, A. Phillips, W. El-Sadr, C.I. Hatleberg, C. Pradier, F. Bonnet, M. Law, S. De Wit, C. Sabin, J.D. Lundgren, H.C. Bucher, G. Calvo, F. Dabis, L. Morfeldt, R. Weber, A. Lind-Thomsen, R. Salbol Brandt, M. Hillebreght, S. Zaheri, F.W.N.M. Wit, A. Scherrer, F. Schoni-Affolter, M. Rickenbach, A. Tavelli, I. Fanti, O. Leleux, J. Mourali, F. Le Marec, E. Boerg, E. Thulin, A. Sundstrom, G. Bartsch, G. Thompsen, C. Necsoi, M. Delforge, E. Fontas, C. Caissotti, K. Dollet, S. Mateu, F. Torres, K. Petoumenos, A. Blance, R. Huang, R. Puhr, K. Gronborg Laut, D. Kristensen, D.A. Kamara, C.J. Smith, D. Raben, C. Matthews, A. Bojesen, A.L. Grevsen, B. Powderly, N. Shortman, C. Moecklinghoff, G. Reilly, C. Smit, M. Ross, C.A. Fux, P. Morlat, N. Friis-Moller, J. Kowalska, J. Bohlius, M. Bower, G. Fatkenheuer, A. Grulich, A. Sjol, P. Meidahl, J.S. Iversen, M. Hillebregt, J.M. Prins, T.W. Kuijpers, H.J. Scherpbier, J.T.M. Van Der Meer, M.H. Godfried, T. Van Der Poll, F.J.B. Nellen, S.E. Geerlings, M. Van Vugt, D. Pajkrt, J.C. Bos, W.J. Wiersinga, M. Van Der Valk, A. Goorhuis, J.W. Hovius, J. Van Eden, A. Henderiks, A.M.H. Van Hes, M. Mutschelknauss, H.E. Nobel, F.J.J. Pijnappel, S. Jurriaans, N.K.T. Back, H.L. Zaaijer, B. Berkhout, M.T.E. Cornelissen, C.J. Schinkel, X.V. Thomas, M. Van Den Berge, A. Stegeman, S. Baas, L. Hage De Looff, D. Versteeg, M.J.H. Pronk, H.S.M. Ammerlaan, E.S. de Munnik, A.R. Jansz, J. Tjhie, M.C.A. Wegdam, B. Deiman, V. Scharnhorst, A. Van Der Plas, A.M. Weijsenfeld, M.E. Van Der Ende, T.E.M.S. de Vries-Sluijs, E.C.M. van Gorp, C.A.M. Schurink, J.L. Nouwen, A. Verbon, B.J.A. Rijnders, H.I. Bax, M. Van Der Feltz, N. Bassant, J.E.A. Van Beek, M. Vriesde, L.M. Van Zonneveld, A. De Oude-Lubbers, H.J. Van Den Berg-Cameron, F.B. Bruinsma-Broekman, J. de Groot, M. De Zeeuw-De Man, C.A.B. Boucher, M.P.G. Koopmans, J.J.A. van Kampen, S.D. Pas, G.J.A. Driessen, A.M.C. van Rossum, L.C. Van Der Knaap, E. Visser, J. Branger, A. Rijkeboer-Mes, C.J.H.M. Duijf-Van De Ven, E.F. Schippers, C. van Nieuwkoop, J.M. van IJperen, J. Geilings, G. van der Hut, P.F.H. Franck, A. Van Eeden, W. Brokking, M. Groot, L.J.M. Elsenburg, M. Damen, I.S. Kwa, P.H.P. Groeneveld, J.W. Bouwhuis, J.F. Van Den Berg, A.G.W. Van Hulzen, G.L. Van Der Bliek, P.C.J. Bor, P. Bloembergen, M.J.H.M. Wolfhagen, G.J.H.M. Ruijs, F.P. Kroon, M.G.J. De Boer, M.P. Bauer, H. Jolink, A.M. Vollaard, W. Dorama, N. Van Holten, E.C.J. Claas, E. Wessels, J.G. Den Hollander, K. Pogany, A. Roukens, M. Kastelijns, J.V. Smit, E. Smit, D. Struik-Kalkman, C. Tearno, M. Bezemer, T. van Niekerk, O. Pontesilli, S.H. Lowe, A.M.L. Oude Lashof, D. Posthouwer, R.P. Ackens, J. Schippers, R. Vergoossen, B. Weijenberg-Maes, I.H.M. van Loo, T.R.A. Havenith, E.M.S. Leyten, L.B.S. Gelinck, A. van Hartingsveld, C. Meerkerk, G.S. Wildenbeest, J.A.E.M. Mutsaers, C.L. Jansen, J.W. Mulder, S.M.E. Vrouenraets, F.N. Lauw, M.C. van Broekhuizen, H. Paap, D.J. Vlasblom, P.H.M. Smits, S. Weijer, R. El Moussaoui, A.S. Bosma, M.G.A. van Vonderen, D.P.F. van Houte, L.M. Kampschreur, K. Dijkstra, S. Faber, J. Weel, G.J. Kootstra, C.E. Delsing, M. van der Burg-Van de Plas, H. Heins, E. Lucas, W. Kortmann, G. van Twillert, J.W.T. Cohen Stuart, B.M.W. Diederen, F.A. van Truijen-Oud, W.A. van der Reijden, R. Jansen, K. Brinkman, G.E.L. van den Berk, W.L. Blok, P.H.J. Frissen, K.D. Lettinga, W.E.M. Schouten, J. Veenstra, J.C. Brouwer, F.G. Geerders, K. Hoeksema, J.M. Kleene, B.I. van der Meche, M. Spelbrink, H. Sulman, A.J.M. Toonen, S. Wijnands, D. Kwa, E. Witte, P.P. Koopmans, M. Keuter, A.J.A.M. van der Ven, H.J.M. ter Hofstede, A.S.M. Dofferhoff, R. van Crevel, M. Albers, M.E.W. Bosch, K.J.T. Grintjes-Huisman, J.B. Zomer, F.F. Stelma, J. Rahamat-Langendoen, D. Burger, C. Richter, H.E. Gisolf, J.R. Hassing, G. ter Beest, P.H.M. van Bentum, N. Langebeek, R. Tiemessen, C.M.A. Swanink, S.F.L. van Lelyveld, R. Soetekouw, N. Hulshoff, L.M.M. van der Prijt, J. van der Swaluw, N. Bermon, B.L. Herpers, D. Veenendaal, W.D.M. Verhagen, M. van Wijk, M.E.E. van Kasteren, E.A. Brouwer, B.A.F.M. de Kruijf-Van de Wiel, M. Kuipers, R.M.W.J. Santegoets, B. van der Ven, H.J. Marcelis, A.G.M. Buiting, J.P. Kabel, W.F.W. Bierman, H. Scholvinck, R.K. Wilting, Y. Stienstra, H. de Groot-De Jonge, A.P. van der Meulen, A.D. de Weerd, J. Ludwig-Roukema, H.G.M. Niesters, A. Riezebos-Brilman, C.C. van Leer-Buter, M. Knoester, A.I.M. Hoepelman, T. Mudrikova, M.P. Ellerbroek, J.J. Oosterheert, E.J. Arends, E.R. Barth, M.W.M. Wassenberg, M.E. Schadd, D.H.M. van Elst-Laurijssen, B.E. van Oers-Hazelzet, S. Vervoort, M. van Berkel, R. Schuurman, F. Verduyn-Lunel, A.M.J. Wensing, E.J.G. Peters, A.M. van Agtmael, M. Bomers, J. de Vocht, M. Heitmuller, M.L. Laan, M.A. Pettersson, C.M.J.E. Vandenbroucke-Grauls, W.C. Ang, S.P.M. Geelen, T.F.W. Wolfs, J.L. Bont, N. Nauta, O.D. Bezemer, I.A. van Sighem, S.T. Boender, A. de Jong, D. Bergsma, P. Hoekstra, A. de Lang, S. Grivell, A. Jansen, J.M. Rademaker, M. Raethke, R. Meijering, S. Schnorr, L. de Groot, M. van den Akker, Y. Bakker, E. Claessen, A. El Berkaoui, J. Koops, E. Kruijne, C. Lodewijk, L. Munjishvili, B. Peeck, C. Ree, R. Regtop, Y. Ruijs, T. Rutkens, L. van de Sande, M. Schoorl, A. Timmerman, E. Tuijn, L. Veenenberg, S. van der Vliet, A. Wisse, T. Woudstra, B. Tuk, M. Dupon, V. Gaborieau, D. Lacoste, D. Malvy, P. Mercie, D. Neau, L.J. Pellegrin, S. Tchamgoue, E. Lazaro, C. Cazanave, M. Vandenhende, O.M. Vareil, Y. Gerard, P. Blanco, S. Bouchet, D. Breilh, H. Fleury, I. Pellegrin, G. Chene, R. Thiebaut, L. Wittkop, S. Lawson-Ayayi, A. Gimbert, S. Desjardin, L. Lacaze-Buzy, V. Petrov-Sanchez, N. Andre, K. Bernard, O. Caubet, L. Caunegre, I. Chossat, C. Courtault, A.F. Dauchy, D. Dondia, P. Duffau, H. Dutronc, S. Farbos, I. Faure, H. Ferrand, C. Greib, M. Hessamfar, Y. Imbert, P. Lataste, J. Marie, M. Mechain, E. Monlun, A. Ochoa, T. Pistone, I. Raymond, C.M. Receveur, P. Rispal, L. Sorin, C. Valette, J.F. Viallard, H. Wille, G. Wirth, M. Lafon, P. Trimoulet, P. Bellecave, C. Tumiotto, F. Haramburu, G. Miremeont-Salame, J.M. Blaizeau, M. Decoin, C. Hannapier, E. Lenaud, A. Pougetoux, S. Delveaux, C. D'Ivernois, F. Diarra, B. Uwamaliya-Nziyumvira, G. Palmer, V. Conte, V. Sapparrart, R. Moore, S. Edwards, J. Hoy, K. Watson, N. Roth, H. Lau, M. Bloch, D. Baker, A. Carr, D. Cooper, M. O'Sullivan, D. Nolan, G. Guelfi, P. Domingo, A.M. Sambeat, J. Gatell, E. Del Cacho, J. Cadafalch, M. Fuster, C. Codina, G. Sirera, A. Vaque, M. Delforge, N. Clumeck, F.A. Gennotte, M. Gerard, K. Kabeya, D. Konopnicki, A. Libois, C. Martin, C.M. Payen, P. Semaille, Y. Van Laethem, J. Neaton, M.W. El-Sadr, E. Krum, G. Thompson, D. Wentworth, R. Luskin-Hawk, E. Telzak, I.D. Abrams, D. Cohn, N. Markowitz, R. Arduino, D. Mushatt, G. Friedland, G. Perez, E. Tedaldi, E. Fisher, F. Gordin, R.L. Crane, J. Sampson, J. Baxter, B. Gazzard, A. Horban, I. Karpov, C. Pedersen, M. Ristola, J. Rockstroh, L. Peters, H.A. Fischer, F.J. Larsen, D. Podlekareva, A. Cozzi-Lepri, L. Shepherd, A. Schultze, S. Amele, M. Losso, M. Kundro, B. Schmied, R. Zangerle, A. Vassilenko, M.V. Mitsura, D. Paduto, E. Florence, L. Vandekerckhove, V. Hadziosmanovic, J. Begovac, L. Machala, D. Jilich, D. Sedlacek, G. Kronborg, T. Benfield, J. Gerstoft, T. Katzenstein, F.N. Moller, L. Ostergaard, L. Wiese, N.L. Nielsen, K. Zilmer, J. Smidt, I. Aho, J.P. Viard, P.M. Girard, C. Duvivier, R. Schmidt, O. Degen, J.H. Stellbrink, C. Stefan, J. Bogner, G. Fatkenheuer, N. Chkhartishvili, P. Gargalianos, G. Xylomenos, K. Armenis, H. Sambatakou, J. Szlavik, M. Gottfredsson, F. Mulcahy, I. Yust, D. Turner, M. Burke, E. Shahar, G. Hassoun, H. Elinav, M. Haouzi, D. Elbirt, M.Z. Sthoeger, R. Esposito, I. Mazeu, C. Mussini, F. Mazzotta, A. Gabbuti, V. Vullo, M. Lichtner, M. Zaccarelli, A. Antinori, R. Acinapura, M. Plazzi, A. Lazzarin, A. Castagna, N. Gianotti, M. Galli, A. Ridolfo, B. Rozentale, V. Uzdaviniene, R. Matulionyte, T. Staub, R. Hemmer, V. Ormaasen, A. Maeland, J. Bruun, B. Knysz, J. Gasiorowski, M. Inglot, E. Bakowska, R. Flisiak, A. Grzeszczuk, M. Parczewski, K. Maciejewska, B. Aksak-Was, M. Beniowski, E. Mularska, T. Smiatacz, M. Gensing, E. Jablonowska, E. Malolepsza, K. Wojcik, I. Mozer-Lisewska, L. Caldeira, K. Mansinho, F. Maltez, R. Radoi, C. Oprea, A. Panteleev, O. Panteleev, A. Yakovlev, T. Trofimora, I. Khromova, E. Kuzovatova, E. Borodulina, E. Vdoushkina, D. Jevtovic, J. Tomazic, M.J. Miro, S. Moreno, J.M. Rodriguez, B. Clotet, A. Jou, R. Paredes, C. Tural, J. Puig, I. Bravo, M. Gutierrez, G. Mateo, M.J. Laporte, K. Falconer, A. Thalme, A. Sonnerborg, A. Blaxhult, L. Flamholc, M. Cavassini, A. Calmy, H. Furrer, M. Battegay, P. Schmid, A. Kuznetsova, G. Kyselyova, M. Sluzhynska, A.M. Johnson, E. Simons, C. Orkin, J. Weber, G. Scullard, A. Clarke, C. Leen, G. Thulin, A. Sundstrom, B. Akerlund, K. Koppel, A. Karlsson, C. Hakangard, F. Castelli, R. Cauda, G. Di Perri, R. Iardino, G. Ippolito, C.G. Marchetti, F.C. Perno, F. von Schloesser, P. Viale, A. Antinori, F. Ceccherini-Silberstein, E. Girardi, S. Lo Caputo, M. Puoti, M. Andreoni, A. Ammassari, C. Balotta, A. Bandera, P. Bonfanti, S. Bonora, M. Borderi, A. Calcagno, L. Calza, R.M. Capobianchi, A. Cingolani, P. Cinque, A. De Luca, A. Di Biagio, A. Gori, G. Guaraldi, G. Lapadula, G. Madeddu, F. Maggiolo, S. Marcotullio, L. Monno, S. Nozza, E. Quiros Roldan, R. Rossotti, S. Rusconi, M.M. Santoro, A. Saracino, L. Galli, P. Lorenzini, A. Rodano, M. Shanyinde, F. Carletti, S. Carrara, A. Di Caro, S. Graziano, F. Petrone, G. Prota, S. Quartu, S. Truffa, A. Giacometti, A. Costantini, V. Barocci, G. Angarano, C. Santoro, C. Suardi, V. Donati, G. Verucchi, C. Minardi, T. Quirino, C. Abeli, E.P. Manconi, P. Piano, B. Cacopardo, B. Celesia, J. Vecchiet, K. Falasca, A. Pan, S. Lorenzotti, L. Sighinolfi, D. Segala, F. Vichi, G. Cassola, C. Viscoli, A. Alessandrini, N. Bobbio, G. Mazzarello, C. Mastroianni, V. Belvisi, I. Caramma, A. Chiodera, P. Milini, G. Rizzardini, C.M. Moioli, R. Piolini, L.A. Ridolfo, S. Salpietro, C. Tincati, C. Puzzolante, N. Abrescia, A. Chirianni, G. Borgia, R. Orlando, G. Bonadies, F. Di Martino, I. Gentile, L. Maddaloni, M.A. Cattelan, S. Marinello, A. Cascio, C. Colomba, F. Baldelli, E. Schiaroli, G. Parruti, F. Sozio, G. Magnani, A.M. Ursitti, A. Cristaudo, G. Baldin, M. Capozzi, S. Cicalini, L. Fontanelli Sulekova, G. Iaiani, A. Latini, I. Mastrorosa, S. Savinelli, A. Vergori, M. Cecchetto, F. Viviani, P. Bagella, B. Rossetti, A. Franco, R. Fontana Del Vecchio, D. Francisci, C. Di Giuli, P. Caramello, C.G. Orofino, M. Sciandra, M. Bassetti, A. Londero, G. Pellizzer, V. Manfrin, G. Starnini, A. Ialungo, P. Dellamonica, E. Bernard, J. Courjon, E. Cua, F. De Salvador-Guillouet, J. Durant, C. Etienne, S. Ferrando, V. Mondain-Miton, A. Naqvi, I. Perbost, S. Pillet, B. Prouvost-Keller, P. Pugliese, V. Rio, K. Risso, M.P. Roger, V. Aubert, E. Bernasconi, A. Ciuffi, G. Dollenmaier, M. Egger, L. Elzi, J. Fehr, J. Fellay, F.H. Gunthard, D. Haerry, B. Hasse, H.H. Hirsch, M. Hoffmann, I. Hosli, C. Kahlert, L. Kaiser, O. Keiser, T. Klimkait, D.R. Kouyos, H. Kovari, B. Ledergerber, G. Martinetti, B. Martinez de Tejada, C. Marzolini, J.K. Metzner, N. Muller, D. Nicca, G. Pantaleo, P. Paioni, A. Rauch, C. Rudin, R. Speck, M. Stockle, P. Tarr, A. Trkola, P. Vernazza, G. Wandeler, S. Yerly. - In: ANNALS OF INTERNAL MEDICINE. - ISSN 0003-4819. - 174:6(2021 Jun), pp. 768-776. [10.7326/M20-5226]

Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy: A multinational prospective cohort study

A. D'Arminio Monforte;A. Bandera
Membro del Collaboration Group
;
A. Gori
Membro del Collaboration Group
;
S. Rusconi;C. Tincati;
2021

Abstract

Background: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. Objective: To estimate the long-term risk difference for cancer with the immediate ART strategy. Design: Multinational prospective cohort study. Setting: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. Participants: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). Measurements: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts < 350 and < 500 × 109 cells/L) ART initiation strategies. Results: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. Limitation: Potential residual confounding due to observational study design. Conclusion: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. Primary Funding Source: Highly Active Antiretroviral Therapy Oversight Committee.
Adult; Anti-HIV Agents; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Incidence; Male; Middle Aged; Neoplasms; Prospective Studies; Risk Factors; Viral Load; Time-to-Treatment
Settore MED/17 - Malattie Infettive
giu-2021
Article (author)
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