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J Infect Dis. 2013 May 1;207(9):1359-69. doi: 10.1093/infdis/jit043. Epub 2013 Feb 4.

Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D study.

Collaborators (728)

Dabis F, El-Sadr W, Pradier C, Reiss P, Kirk O, Weber R, Law M, Morfeldt L, de Wit S, Calvo G, d'Arminio Monforte A, Dabis F, El-Sadr W, Pradier C, Reiss P, Kirk O, Weber R, Law M, de Wit S, d'Arminio Monforte A, Shortman N, Butcher D, Rode R, Franquet X, Powderly W, Sabin C, Phillips A, Lundgren J, Ryom L, Sabin C, Kamara D, Smith C, Phillips A, Mocroft A, Tverland J, Nielsen J, Lundgren J, 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, Kamara D, Smith C, Worm S, Reiss P, Ross M, Fux C, Morlat P, Moranne O, Lundgren J, de Wolf F, Zaheri S, Hillebregt M, Gras L, Prins JM, Kuijpers TW, Scherpbier HJ, Boer K, van der Meer JT, Wit FW, Godfried MH, Reiss P, van der Poll T, Nellen FJ, Lange JM, Geerlings SE, van Vugt M, Vrouenraets SM, Pajkrt D, van der Valk M, Schreij G, Lowe S, Oude Lashof A, Pronk MJ, Bravenboer B, van der Ende ME, de Vries-Sluijs TE, Schurink CA, van der Feltz M, Nouwen JL, Gelinck LB, Verbon A, Rijnders BJ, Slobbe L, Hartwig NG, Driessen GJ, Branger J, Kauffmann RH, Schippers EF, Groeneveld PH, Alleman MA, Bouwhuis JW, ten Kate RW, Soetekouw R, Kroon FP, van den Broek PJ, van Dissel JT, Arend SM, van Nieuwkoop C, de Boer MG, Jolink H, den Hollander JG, Pogany K, van Twillert G, Kortmann W, Vriesendorp R, Leyten EM, ten Napel CH, Kootstra GJ, Brinkman K, Blok WL, Frissen PH, Schouten WE, van den Berk GE, Juttmann JR, van Kasteren ME, Brouwer AE, Veenstra J, Lettinga KD, Mulder JW, van Gorp EC, Smit PM, Weijer S, van Eeden A, Verhagen DW, Sprenger HG, Doedens R, Scholvinck EH, van Assen S, Stek CJ, Koopmans PP, de Groot R, Keuter M, van der Ven AJ, ter Hofstede HJ, van der Flier M, Brouwer AM, Dofferhoff AS, Hoepelman AI, Mudrikova T, Schneider MM, Jaspers CA, Ellerbroek PM, Peters EJ, Maarschalk-Ellerbroek LJ, Oosterheert JJ, Arends JE, Wassenberg MW, van der Hilst JC, Danner SA, van Agtmael MA, de Vocht J, Perenboom RM, Claessen FA, Bierman WF, de Jong EV, bij de Vaate EA, Geelen SP, Wolfs TF, Richter C, van der Berg JP, Gisolf EH, van den Berge M, Stegeman A, van Houte DP, Polée MB, van Vonderen MG, Winkel C, Duits AJ, Dabis F, Bruyand M, Chêne G, Dabis F, Lawson-Ayayi S, Thiébaut R, Bonnal F, Bonnet F, Bernard N, Caunègre L, Cazanave C, Ceccaldi J, Chambon D, Chossat I, Dauchy FA, De Witte S, Dupon M, Duffau P, Dutronc H, Farbos S, Gaborieau V, Gemain MC, Gerard Y, Greib C, Hessamfar M, Lacoste D, Lataste P, Lafarie S, Lazaro E, Malvy D, Meraud JP, Mercié P, Monlun E, Morlat P, Neau D, Ochoa A, Pellegrin JL, Pistone T, Ragnaud JM, Receveur MC, Tchamgoué S, Vandenhende MA, Viallard JF, Moreau JF, Pellegrin I, Fleury H, Lafon ME, Masquelier B, Trimoulet P, Breilh D, Haramburu F, Miremont-Salamé G, Blaizeau MJ, Decoin M, Delaune J, Delveaux S, D'Ivernois C, Hanapier C, Leleux O, Uwamaliya-Nziyumvira B, Sicard X, Geffard S, Palmer G, Touchard D, Bonnet F, Dupon M, Mercié P, Morlat P, Ragnaud JM, Pellegrin JL, Dabis F, 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, Chuah M, 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, 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 W, 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, Lundgren J, Kirk O, Mocroft A, Cozzi-Lepri A, Grint D, Podlekareva D, Kjær J, Peters L, Tverland J, Fischer AH, Nielsen J, Losso M, Elias C, Ramos Mejia JM, 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, Jilich D, 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, Bickel M, Goethe JW, Bogner J, 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, Cotugno AD, Antonucci G, Testa A, Narciso P, Vlassi C, Zaccarelli M, Lazzarin A, Castagna A, Gianotti N, Galli M, Ridolfo A, Sacco L, 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, Babes V, Rakhmanova A, Zakharova n, Jevtovic D, Mokráš M, Staneková D, 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, Castelli F, Cauda R, d'Arminio Monforte A, Di Perri G, Galli M, Iardino R, Ippolito G, Lazzarin A, Perno CF, Armignacco O, Viale PL, Von Schlosser F, Andreoni M, Antinori A, Balotta C, Bonfanti P, Bonora S, Borderi M, Capobianchi MR, Castagna A, Ceccherini-Silberstein F, Cinque P, Cozzi-Lepri A, d'Arminio Monforte A, De Luca A, Gargiulo M, Gervasoni C, Girardi E, Gori A, Guaraldi G, Lichtner M, Lo Caputo S, Madeddu G, Maggiolo F, Marchetti G, Marcotullio S, Monno L, Murri R, Mussini C, Puoti M, Torti C, Cozzi-Lepri A, Cicconi P, Fanti I, Formenti T, Galli L, Lorenzini P, Giacometti A, Costantini A, Riva A, Angarano G, Monno L, Carrisa C, Maggiolo F, Lazzari G, Viale PL, Borderi M, Verucchi G, Castelli F, Torti C, 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, Chiodera A, Castelli P, Galli M, Lazzarin A, Rizzardini G, Puoti M, d'Arminio Monforte A, Ridolfo AL, Piolini R, Castagna A, Salpietro S, Galli A, Bigoloni A, Spagnuolo V, Carenzi L, Zucchi P, Moioli MC, Rossotti R, Cicconi P, Formenti T, Mussini C, Bisio L, Gori A, Lapadula G, Abrescia N, Chirianni A, Guida MG, Gargiulo M, Baldelli F, Belfiori B, Parruti G, Ursini T, Magnani G, Ursitti MA, Cauda R, Andreoni M, Antinori A, Tozzi V, Vullo V, De Luca A, d'Avino A, Zaccarelli M, Gallo L, Nicastro E, Acinapura R, Capozzi M, Libertone R, Lichtner M, Tebano G, Mura MS, Madeddu G, Caramello P, Di Perri G, Sciandra M, Orofino GC, 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, Barth J, Battegay M, Bernasconi E, Böni J, Bucher HC, Burton-Jeangros C, Calmy A, Cavassini M, Cellerai C, Dubs R, Egger M, Elzi L, Fehr J, Flepp M, Francioli P, Furrer H, Fux CA, Gorgievski M, Günthard H, Hasse B, Hirsch HH, Hirschel B, Hösli I, Kahlert C, Kaiser L, Keiser O, Kind C, Klimkait T, Kovari H, Ledergerber B, Martinetti G, Martinez de Tejada B, Müller N, Nadal D, Pantaleo G, Rauch A, Regenass S, Rickenbach M, Rudin C, Schmid P, Schultze D, Schöni-Affolter F, Schüpbach J, Speck R, Taffé P, Telenti A, Trkola A, Vernazza P, von Wyl V, Weber R, Yerly S.

Abstract

BACKGROUND:

Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)-positive persons with initially normal renal function is unknown.

METHODS:

D:A:D study participants with an estimated glomerular filtration rate (eGFR) of ≥ 90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ≤ 70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ≤ 60 mL/min (a value indicative of moderately severe chronic kidney disease [CKD]) or until the last eGFR measurement during follow-up. An eGFR was considered confirmed if it was detected at 2 consecutive measurements ≥ 3 months apart. Predictors and eGFR-related ARV discontinuations were identified using Poisson regression.

RESULTS:

Of 22 603 persons, 468 (2.1%) experienced a confirmed eGFR of ≤ 70 mL/min (incidence rate, 4.78 cases/1000 person-years of follow-up [95% confidence interval {CI}, 4.35-5.22]) and 131 (0.6%) experienced CKD (incidence rate, 1.33 cases/1000 person-years of follow-up [95% CI, 1.10-1.56]) during a median follow-up duration of 4.5 years (interquartile range [IQR], 2.7-6.1 years). A current eGFR of 60-70 mL/min caused significantly higher rates of discontinuation of tenofovir (adjusted incidence rate ratio [aIRR], 1.72 [95% CI, 1.38-2.14]) but not other ARVs compared with a current eGFR of ≥ 90 mL/min. Cumulative tenofovir use (aIRR, 1.18/year [95% CI, 1.12-1.25]) and ritonavir-boosted atazanavir use (aIRR, 1.19/year [95% CI, 1.09-1.32]) were independent predictors of a confirmed eGFR of ≤ 70 but were not significant predictors of CKD whereas ritonavir-boosted lopinavir use was a significant predictor for both end points (aIRR, 1.11/year [95% CI, 1.05-1.17] and 1.22/year [95% CI, 1.16-1.28], respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs.

CONCLUSIONS:

Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment in HIV-positive persons without preexisting renal impairment. Increased tenofovir discontinuation rates with decreasing eGFR may have prevented further deteriorations. After discontinuation, the ARV-associated incidence rates decreased.

PMID:
23382571
[PubMed - indexed for MEDLINE]
PMCID:
PMC3610424
Free PMC Article
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