Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study

Amanda Mocroft; Jens D Lundgren; Michael Ross; Christoph A Fux; Peter Reiss; Olivier Moranne; Philippe Morlat; Antonella d'Arminio Monforte; Ole Kirk; Lene Ryom; Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) Study

doi:10.1016/S2352-3018(15)00211-8

Cumulative and current exposure to potentially nephrotoxic antiretrovirals and development of chronic kidney disease in HIV-positive individuals with a normal baseline estimated glomerular filtration rate: a prospective international cohort study

Lancet HIV. 2016 Jan;3(1):e23-32. doi: 10.1016/S2352-3018(15)00211-8. Epub 2015 Nov 17.

Collaborators

Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) Study:
D Steering, B Powderly, N Shortman, C Moecklinghoff, G Reilly, X Franquet, L Ryom, C I Hatleberg, C A Sabin, D Kamara, C Smith, A Phillips, A Mocroft, A Bojesen, A L Grevsen, C Matthews, D Raben, J D Lundgren, R S Brandt, M Rickenbach, I Fanti, M Hillebreght, S Zaheri, L Gras, E Pernot, J Mourabi, A Sundström, M Delforge, E Fontas, F Torres, H McManus, S Wright, D Kristensen, A Sjøl, P Meidahl, J Helweg-Larsen, J Schmidt Iversen, L Ryom, A Mocroft, O Kirk, P Reiss, C Smit, M Ross, C A Fux, P Morlat, O Moranne, D A Kamara, C Smith, J D Lundgren, C Smith, L Ryom, A Phillips, R Weber, P Morlat, C Pradier, P Reiss, N Friis-Møller, J Kowalska, J D Lundgren, C Sabin, M Law, A d'Arminio Monforte, F Dabis, M Bruyand, F Bonnet, P Reiss, C Smith, D A Kamara, M Bower, G Fätkenheuer, A Donald, A Grulich, L Ryom, J D Lundgren, J M Prins, T W Kuijpers, H J Scherpbier, J T M van der Meer, F W M N Wit, M H Godfried, P Reiss, 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, A M Westerman, S Jurriaans, N K T Back, H L Zaaijer, B Berkhout, M T E Cornelissen, C J Schinkel, X V Thomas, Admiraal De Ruyter Ziekenhuis, M van den Berge, A Stegeman, S Baas, L Hage de Looff, D Versteeg, M J H Pronk, H S M Ammerlaan, E M H M Korsten-Vorstermans, E S de Munnik, A R Jansz, J Tjhie, M C A Wegdam, B Deiman, V Scharnhorst, Emma Kinderziekenhuis, 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, R J Hassing, 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, de Zeeuw de Man, M J Broekhoven-Kruijne, M Schutten, A D M E Osterhaus, C A B Boucher, G J A Driessen, A M C van Rossum, L C van der Knaap, E Visser, J Branger, C J H M Duijf-van de Ven, Den Haag, E F Schippers, C van Nieuwkoop, R W Brimicombe, M van IJperen, G van der Hut, P F H Franck, A van Eeden, W Brokking, M Groot, 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, Kennemer Gasthuis, S F L van Lelyveld, R Soetekouw, N Hulshoff, L M M van der Prijt, M Schoemaker, N Bermon, W A van der Reijden, R Jansen, B L Herpers, D Veenendaal, F P Kroon, S M Arend, M G J de Boer, M P Bauer, H Jolink, A M Vollaard, W Dorama, C Moons, E C J Claas, A C M Kroes, J G den Hollander, K Pogany, M Kastelijns, J V Smit, E Smit, M Bezemer, T van Niekerk, O Pontesilli, S H Lowe, A Oude Lashof, D Posthouwer, R P Ackens, J Schippers, R Vergoossen, B Weijenberg Maes, P H M Savelkoul, I H Loo, M C Zuiderzee, S Weijer, R El Moussaoui, M Heitmuller, M Heitmuller, W Kortmann, G van Twillert, J W T Cohen Stuart, B M W Diederen, D Pronk, F A van Truijen-Oud, W A van der Reijden, R Jansen, E M S Leyten, L B S Gelinck, A van Hartingsveld, C Meerkerk, G S Wildenbeest, J A E M Mutsaers, C L Jansen, M G A van Vonderen, D P F van Houte, K Dijkstra, S Faber, J Weel, G J Kootstra, C E Delsing, M van der Burgvan de Plas, H Heins, E Lucas, K Brinkman, P H J Frissen, W L Blok, W E M Schouten, A S Bosma, C J Brouwer, G F Geerders, K Hoeksema, M J Kleene, I B van der Meché, A J M Toonen, S Wijnands, M L van Ogtrop, R Jansen, 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, B J Zomer, F F Stelma, D Burger, C Richter, J P van der Berg, E H Gisolf, G ter Beest, P H M van Bentum, N Langebeek, R Tiemessen, C M A Swanink, J Veenstra, K D Lettinga, M Spelbrink, H Sulman, M Spelbrink, E Witte, M Damen, P G H Peerbooms, J W Mulder, S M E Vrouenraets, F N Lauw, M C van Broekhuizen, H Paap, D J Vlasblom, E Oudmaijer Sanders, P H M Smits, A W Rosingh, D W M Verhagen, J Geilings, M E E van Kasteren, A E Brouwer, B A F M de Kruijf-van de Wiel, M Kuipers, R M W J Santegoets, B van der Ven, J H Marcelis, A G M Buiting, P J Kabel, W F W Bierman, H G Sprenger, E H Scholvinck, S van Assen, K R Wilting, Y Stienstra, H de Groot-de Jonge, P A van der Meulen, D A de Weerd, H G M Niesters, A Riezebos-Brilman, C C van Leer-Buter, A I M Hoepelman, M M E Schneider, T Mudrikova, P M Ellerbroek, J J Oosterheert, J E Arends, R E Barth, M W M Wassenberg, D H M van Elst-Laurijssen, L M Laan, E E B van Oers-Hazelzet, J Patist, S Vervoort, H E Nieuwenhuis, R Frauenfelder, R Schuurman, F Verduyn-Lunel, A M J Wensing, E J G Peters, M A van Agtmael, R M Perenboom, M Bomers, J de Vocht, L J M Elsenburg, A M Pettersson, C M J E Vandenbroucke-Grauls, C W Ang, S P M Geelen, T F W Wolfs, L J Bont, N Nauta, P Reiss, D O Bezemer, L Gras, A I van Sighem, C Smit, S Zaheri, M Hillebregt, V Kimmel, Y Tong, B Lascaris, R van den Boogaard, P Hoekstra, A de Lang, M Berkhout, S Grivell, A Jansen, L de Groot, M van den Akker, D Bergsma, C Lodewijk, R Meijering, B Peeck, M Raethke, C Ree, R Regtop, Y Ruijs, M Schoorl, E Tuijn, L Veenenberg, T Woudstra, Y Bakker, A de Jong, M Broekhoven, E Claessen, M J Rademaker, L Munjishvili, E Kruijne, B Tuk, F Bonnet, F Dabis, F Bonnet, S Bouchet, D Breilh, G Chêne, F Dabis, M Dupon, H Fleury, V Gaborieau, D Lacoste, D Malvy, P Mercié, P Morlat, D Neau, I Pellegrin, J L Pellegrin, S Tchamgoué, M Bruyand, G Chêne, F Dabis, C Fagard, S Lawson-Ayayi, L Richert, R Thiébaut, L Wittkop, K André, F Bonnet, N Bernard, L Caunègre, C Cazanave, J Ceccaldi, I Chossat, C Courtault, F A Dauchy, S De Witte, D Dondia, M Dupon, A Dupont, P Duffau, H Dutronc, S Farbos, I Faure, V Gaborieau, Y Gerard, C Greib, M Hessamfar-Joseph, Y Imbert, D Lacoste, P Lataste, E Lazaro, D Malvy, J Marie, M Mechain, J P Meraud, P Mercié, E Monlun, P Morlat, D Neau, A Ochoa, J L Pellegrin, M Pillot-Debelleix, T Pistone, I Raymond, M C Receveur, P Rispal, L Sorin, S Tchamgoué, C Valette, M A Vandenhende, M O Vareil, J F Viallard, H Wille, G Wirth, J F Moreau, I Pellegrin, H Fleury, M E Lafon, S Reigadas, P Trimoulet, S Bouchet, D Breilh, F Haramburu, G Miremont-Salamé, M J Blaizeau, I Crespel, M Decoin, S Delveaux, F Diarra, C D'Ivernois, C Hanappier, D Lacoste, S Lawson-Ayayi, O Leleux, F Le Marec, E Lenaud, J Mourali, E Pernot, A Pougetoux, B Uwamaliya-Nziyumvira, A Tsaranazy, A Valdes, V Conte, I Louis, G Palmer, V Sapparrart, D Touchard, M Law, K Petoumenos, H McManus, S Wright, C Bendall, R Moore, S Edwards, J Hoy, K Watson, N Roth, J Nicholson, M Bloch, T Franic, D Baker, R Vale, A Carr, D Cooper, J Chuah, M Ngieng, D Nolan, J Skett, G Calvo, F Torres, S Mateu, P Domingo, M A Sambeat, J Gatell, E Del Cacho, J Cadafalch, M Fuster, C Codina, G Sirera, A Vaqué, S De Wit, N Clumeck, M Delforge, C Necsoi, N Clumeck, S De Wit, A F Gennotte, M Gerard, K Kabeya, D Konopnicki, A Libois, C Martin, M C Payen, P Semaille, Y Van, J Neaton, G Bartsch, W M El-Sadr, E Krum, 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, M Losso, M Kundro, N Vetter, R Zangerle, I Karpov, A Vassilenko, V M Mitsura, D Paduto, N Clumeck, S De Wit, M Delforge, E Florence, L Vandekerckhove, V Hadziosmanovic, K Kostov, J Begovac, L Machala, D Jilich, D Sedlacek, G Kronborg, T Benfield, J Gerstoft, T Katzenstein, A-B E Hansen, C Pedersen, N F Møller, L Ostergaard, U B Dragsted, L N Nielsen, K Zilmer, Jelena Smidt, M Ristola, I Aho, C Katlama, J-P Viard, P-M Girard, L Cotte, C Pradier, F Dabis, D Neau, C Duvivier, J Rockstroh, R Schmidt, J van Lunzen, O Degen, H J Stellbrink, C Stefan, J Bogner, G Fätkenheuer, N Chkhartishvili, J Kosmidis, P Gargalianos, G Xylomenos, P Lourida, H Sambatakou, D Banhegyi, M Gottfredsson, F Mulcahy, I Yust, D Turner, M Burke, E Shahar, G Hassoun, H Elinav, M Haouzi, Z M Sthoeger, A D'Arminio Monforte, R Esposito, I Mazeu, C Mussini, F Mazzotta, A Gabbuti, V Vullo, M Lichtner, M Zaccarelli, A Antinori, R Acinapura, G D'Offizi, A Lazzarin, A Castagna, N Gianotti, M Galli, A Ridolfo, B Rozentale, V Uzdaviniene, R Matulionyte, T Staub, R Hemmer, P Reiss, V Ormaasen, A Maeland, J Bruun, B Knysz, J Gasiorowski, M Inglot, A Horban, E Bakowska, A Grzeszczuk, R Flisiak, M Parczewski, M Pynka, K Maciejewska, M Beniowski, E Mularska, T Smiatacz, M Gensing, E Jablonowska, E Malolepsza, K Wojcik, I Mozer-Lisewska, M Doroana, L Caldeira, K Mansinho, F Maltez, R Radoi, C Oprea, A Rakhmanova, A Rakhmanova, T Trofimora, I Khromova, E Kuzovatova, D Jevtovic, A Shunnar, D Staneková, J Tomazic, S Moreno, J M Rodriguez, B Clotet, A Jou, R Paredes, C Tural, J Puig, I Bravo, J M Gatell, J M Miró, P Domingo, M Gutierrez, G Mateo, M A Sambeat, J M Laporte, A Blaxhult, L Flamholc, K Falconer, A Thalme, A Sonnerborg, B Ledergerber, R Weber, M Cavassini, A Calmy, H Furrer, M Battegay, L Elzi, P Schmid, E Kravchenko, N Chentsova, V Frolov, G Kutsyna, I Baskakov, S Servitskiy, A Kuznetsova, G Kyselyova, B Gazzard, A M Johnson, E Simons, S Edwards, A Phillips, M A Johnson, A Mocroft, C Orkin, J Weber, G Scullard, M Fisher, C Leen, J Gatell, B Gazzard, A Horban, I Karpov, B Ledergerber, M Losso, A d'Arminio Monforte, C Pedersen, A Rakhmanova, M Ristola, A Phillips, P Reiss, J Lundgren, J Rockstroh, S De Wit, J Rockstroh, S De Wit, A Mocroft, O Kirk, O Kirk, A Mocroft, J Grarup, P Reiss, A Cozzi-Lepri, R Thiebaut, J Rockstroh, D Burger, R Paredes, L Peters, O Kirk, L Peters, C Matthews, A H Fischer, A Bojesen, D Raben, D Kristensen, K Grønborg Laut, J F Larsen, D Podlekareva, A Mocroft, A Phillips, A Cozzi-Lepri, D Grint, L Shepherd, A Schultze, L Morfeldt, G Thulin, A Sundström, B Åkerlund, K Koppel, A Karlsson, L Flamholc, C Håkangård, M Moroni, G Angarano, A Antinori, O Armignacco, A d'Arminio Monforte, F Castelli, R Cauda, G Di Perri, M Galli, R Iardino, G Ippolito, A Lazzarin, C F Perno, F von Schloesser, P Viale, A d'Arminio Monforte, A Antinori, A Castagna, F Ceccherini-Silberstein, A Cozzi-Lepri, E Girardi, S Lo Caputo, C Mussini, M Puoti, M Andreoni, A Ammassari, A Antinori, A d'Arminio Monforte, C Balotta, P Bonfanti, S Bonora, M Borderi, R Capobianchi, A Castagna, F Ceccherini-Silberstein, A Cingolani, P Cinque, A Cozzi-Lepri, A De Luca, A Di Biagio, E Girardi, N Gianotti, A Gori, G Guaraldi, G Lapadula, M Lichtner, S Lo Caputo, G Madeddu, F Maggiolo, G Marchetti, S Marcotullio, L Monno, C Mussini, M Puoti, E Quiros Roldan, S Rusconi, A Cozzi-Lepri, P Cicconi, I Fanti, T Formenti, L Galli, P Lorenzini, A Giacometti, A Costantini, G Angarano, L Monno, C Santoro, F Maggiolo, C Suardi, P Viale, E Vanino, G Verucchi, F Castelli, E Quiros Roldan, C Minardi, T Quirino, C Abeli, P E Manconi, P Piano, J Vecchiet, K Falasca, L Sighinolfi, D Segala, F Mazzotta, S Lo Caputo, G Cassola, G Viscoli, A Alessandrini, R Piscopo, G Mazzarello, C Mastroianni, V Belvisi, P Bonfanti, A P Castelli, M Galli, A Lazzarin, G Rizzardini, M Puoti, A d'Arminio Monforte, A L Ridolfo, R Piolini, A Castagna, S Salpietro, L Carenzi, M C Moioli, P Cicconi, G Marchetti, C Mussini, C Puzzolante, A Gori, G Lapadula, N Abrescia, A Chirianni, M G Guida, M Onofrio, F Baldelli, D Francisci, G Parruti, T Ursini, G Magnani, M A Ursitti, R Cauda, M Andreoni, A Antinori, V Vullo, A Cingolani, A d'Avino, A Ammassari, L Gallo, E Nicastri, R Acinapura, M Capozzi, R Libertone, G Tebano, A Cattelan, M S Mura, G Madeddu, P Caramello, G Di Perri, G C Orofino, S Bonora, M Sciandra, G Pellizzer, V Manfrin, A Rakhmanova, A Rakhmanova, T Trofimora, I Khromova, E Kuzovatova, D Jevtovic, A Shunnar, D Staneková, J Tomazic, S Moreno, J M Rodriguez, B Clotet, A Jou, R Paredes, C Tural, J Puig, I Bravo, J M Gatell, J M Miró, P Domingo, M Gutierrez, G Mateo, M A Sambeat, J M Laporte, A Blaxhult, L Flamholc, K Falconer, A Thalme, A Sonnerborg, B Ledergerber, R Weber, M Cavassini, A Calmy, H Furrer, M Battegay, L Elzi, P Schmid, E Kravchenko, N Chentsova, V Frolov, G Kutsyna, I Baskakov, S Servitskiy, A Kuznetsova, B Gazzard, A M Johnson, E Simons, S Edwards, A Phillips, M A Johnson, A Mocroft, C Orkin, J Weber, G Scullard, M Fisher, C Leen, J Gatell, B Gazzard, A Horban, I Karpov, B Ledergerber, M Losso, A d'Arminio Monforte, C Pedersen, A Rakhmanova, M Ristola, A Phillips, P Reiss, J Lundgren, J Rockstroh, S De Wit, J Rockstroh, S De Wit, A Mocroft, O Kirk, O Kirk, A Mocroft, J Grarup, P Reiss, A Cozzi-Lepri, R Thiebaut, J Rockstroh, D Burger, R Paredes, L Peters, O Kirk, L Peters, C Matthews, A H Fischer, A Bojesen, D Raben, D Kristensen, K Grønborg Laut, J F Larsen, D Podlekareva, A Mocroft, A Phillips, A Cozzi-Lepri, D Grint, L Shepherd, A Schultze, L Morfeldt, G Thulin, A Sundström, K Koppel, A Karlsson, L Flamholc, C Håkangård, M Moroni, G Angarano, A Antinori, O Armignacco, A d'Arminio Monforte, F Castelli, R Cauda, G Di Perri, M Galli, R Iardino, G Ippolito, A Lazzarin, C F Perno, F von Schloesser, P Viale, A d'Arminio Monforte, A Antinori, A Castagna, F Ceccherini-Silberstein, A Cozzi-Lepri, E Girardi, S Lo Caputo, C Mussini, M Puoti, M Andreoni, A Ammassari, A Antinori, A d'Arminio Monforte, C Balotta, P Bonfanti, S Bonora, M Borderi, R Capobianchi, A Castagna, F Ceccherini-Silberstein, A Cingolani, P Cinque, A Cozzi-Lepri, A De Luca, A Di Biagio, E Girardi, N Gianotti, A Gori, G Guaraldi, G Lapadula, M Lichtner, S Lo Caputo, G Madeddu, F Maggiolo, G Marchetti, S Marcotullio, L Monno, C Mussini, M Puoti, E Quiros Roldan, S Rusconi, A Cozzi-Lepri, P Cicconi, I Fanti, T Formenti, L Galli, P Lorenzini, A Giacometti, A Costantini, G Angarano, L Monno, C Santoro, F Maggiolo, C Suardi, P Viale, E Vanino, G Verucchi, F Castelli, E Quiros Roldan, C Minardi, T Quirino, C Abeli, P E Manconi, P Piano, J Vecchiet, K Falasca, L Sighinolfi, D Segala, F Mazzotta, S Lo Caputo, G Cassola, G Viscoli, A Alessandrini, R Piscopo, G Mazzarello, C Mastroianni, V Belvisi, A P Castelli, M Galli, A Lazzarin, G Rizzardini, M Puoti, A d'Arminio Monforte, A L Ridolfo, R Piolini, A Castagna, S Salpietro, L Carenzi, M C Moioli, P Cicconi, G Marchetti, C Mussini, C Puzzolante, A Gori, G Lapadula, N Abrescia, A Chirianni, M G Guida, M Onofrio, F Baldelli, D Francisci, G Parruti, T Ursini, G Magnani, M A Ursitti, R Cauda, M Andreoni, A Antinori, V Vullo, A Cingolani, A d'Avino, A Ammassari, L Gallo, E Nicastri, R Acinapura, M Capozzi, R Libertone, G Tebano, A Cattelan, M S Mura, G Madeddu, P Caramello, G Di Perri, G C Orofino, S Bonora, M Sciandra, G Pellizzer, V Manfrin, C Pradier, E Fontas, K Dollet, C Caissotti, P Dellamonica, E Bernard, E Cua, F De Salvador-Guillouet, J Durant, S Ferrando, B Dunais, V Mondain-Miton, A Naqvi, I Perbost, B Prouvost-Keller, S Pillet, P Pugliese, K Risso, P M Roger, V Aubert, M Battegay, E Bernasconi, J Böni, H C Bucher, C Burton-Jeangros, A Calmy, M Cavassini, G Dollenmaier, M Egger, L Elzi, J Fehr, J Fellay, H Furrer, C A Fux, M Gorgievski, H Günthard, D Haerry, B Hasse, H H Hirsch, M Hoffmann, I Hösli, C Kahlert, L Kaiser, O Keiser, T Klimkait, R Kouyos, H Kovari, B Ledergerber, G Martinetti, B Martinez de Tejada, K Metzner, N Müller, D Nadal, D Nicca, G Pantaleo, A Rauch, S Regenass, M Rickenbach, C Rudin, F Schöni-Affolter, P Schmid, J Schüpbach, R Speck, P Tarr, A Telenti, A Trkola, P Vernazza, R Weber, S Yerly

Affiliations

¹ Department of Infection and Population Health, University College London, London, UK. Electronic address: [email protected].
² CHIP, Department of Infectious Diseases, Section 2100, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
³ Division of Nephrology, Icahn School of Medicine at Mount Sinai School, New York, NY, USA.
⁴ Clinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Aarau, Switzerland.
⁵ Academic Medical Center, Division of Infectious Diseases and Department of Global Health, University of Amsterdam, Amsterdam, Netherlands; Stichting HIV Monitoring, Amsterdam, Netherlands.
⁶ Nephrology Unit, Caremeau University Hospital, Nimes, France; Biostatistics, Epidemiology and Public Health, Institut Universitaire de Recherche Clinique, University of Montpellier, Montpellier, France.
⁷ Université de Bordeaux, INSERM U 897, CHU de Bordeaux, France.
⁸ Clinic of Infectious and Tropical Diseases, Department of Health Sciences, University of Milan, Milan, Italy.

PMID: 26762990
DOI: 10.1016/S2352-3018(15)00211-8

Abstract

Background: Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR).

Methods: In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir.

Findings: Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], p<0·0001), ritonavir-boosted atazanavir (1·20 [1·13-1·26], p<0·0001), and ritonavir-boosted lopinavir (1·11 [1·06-1·16], p<0·0001), but not other ritonavir-boosted protease inhibitors or abacavir.

Interpretation: In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored.

Funding: The Highly Active Antiretroviral Therapy Oversight Committee.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adolescent
Adult
Anti-HIV Agents / adverse effects*
Anti-HIV Agents / therapeutic use
Atazanavir Sulfate / adverse effects
Atazanavir Sulfate / therapeutic use
Australia
Europe
Female
Glomerular Filtration Rate / drug effects*
HIV Infections / complications*
HIV Infections / drug therapy
Humans
Male
Middle Aged
Prospective Studies
Renal Insufficiency, Chronic / etiology*
Renal Insufficiency, Chronic / physiopathology
Tenofovir / adverse effects
Tenofovir / therapeutic use
United States
Young Adult

Substances

Anti-HIV Agents
Atazanavir Sulfate
Tenofovir

Grants and funding

R01 DK108346/DK/NIDDK NIH HHS/United States