Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study-Reference-Cited by-同舟云学术

Antiretroviral Drugs and Risk of Chronic Alanine Aminotransferase Elevation in Human Immunodeficiency Virus (HIV)-Monoinfected Persons: The Data Collection on Adverse Events of Anti-HIV Drugs Study

Published:2016-01-01 Issue:1 Volume:3 Page:
ISSN:2328-8957
Container-title:Open Forum Infectious Diseases
language:en
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Author:

Kovari Helen¹,Sabin Caroline A.²,Ledergerber Bruno¹,Ryom Lene³,Reiss Peter⁴,Law Matthew⁵,Pradier Christian⁶,Dabis Francois⁷,d'Arminio Monforte Antonella⁸,Smith Colette²,de Wit Stephane⁹,Kirk Ole³,Lundgren Jens D.³,Weber Rainer¹,Powderly B.,Shortman N.,Moecklinghoff C.,Reilly G.,Franquet X.,Hatleberg C.I.,Ryom L.,Sabin C.A.,Kamara D.,Smith C.,Phillips A.,Mocroft A.,Bojesen A.,Nielsen J.,Matthews C.,Raben D.,Lundgren J.D.,Salbøl Brandt R.,Rickenbach M.,Fanti I.,Krum E.,Hillebregt M.,Geffard S.,Mourabi Jaohar,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 C.A.,Morlat P.,Moranne O.,Kesselring A.M.,Kamara D.A.,Smith C.,Lundgren J.D.,Smith C.,Ryom L.,Phillips A.,Weber R.,Morlat P.,Pradier C.,Reiss P.,Friis-Møller N.,Kowalska J.,Lundgren J.D.,Sabin C.,Law M.,d'Arminio Monforte A.,Dabis F.,Bruyand M.,Reiss P.,Smith C.,Kamara D.A.,Bower M.,Fätkenheuer G.,Grulich A.,Ryom L.,Lundgren J.D.,Reiss P.,Zaheri S.,Hillebregt M.,Gras L.,Prins J.M.,Kuijpers T.W.,Scherpbier H.J.,van der Meer J.T.M.,Wit F.W.M.N.,Godfried M.H.,Reiss P.,van der Poll T.,Nellen F.J.B.,Lange J.M.A.,Geerlings S.E.,van Vugt M.,Pajkrt D.,Bos J.C.,van der Valk M.,Grijsen M.L.,Wiersinga W.J.,Goorhuis A.,Hovius J.W.R.,Lowe S.,Lashof A. Oude,Posthouwer D.,Pronk M.J.H.,Ammerlaan H.S.M.,van der Ende M.E.,de Vries-Sluijs T.E.M.S.,Schurink C.A.M.,Nouwen J.L.,Verbon A.,Rijnders B.J.A.,van Gorp E.C.M.,van der Feltz M.,Driessen G.J.A.,van Rossum A.M.C.,Branger J.,Schippers E.F.,van Nieuwkoop C.,van Elzakker E.P.,Groeneveld P.H.P.,Bouwhuis J.W.,Soetekouw R.,ten Kate R.W.,Kroon F.P.,van Dissel J.T.,Arend S.M.,de Boer M.G.J.,Jolink H.,ter Vollaard H.J.M.,Bauer M.P.,den Hollander J.G.,Pogany K.,van Twillert G.,Kortmann W.,Cohen Stuart J.W.T.,Diederen B.M.W.,Leyten E.M.S.,Gelinck L.B.S.,Kootstra G.J.,Delsing C.E.,Brinkman K.,Blok W.L.,Frissen P.H.J.,Schouten W.E.M.,van den Berk G.E.L.,van Kasteren M.E.E.,Brouwer A.E.,Veenstra J.,Lettinga K.D.,Mulder J.W.,Vrouenraets S.M.E.,Lauw F.N.,van Eeden A.,Verhagen D.W.M.,Sprenger H.G.,Doedens R.,Scholvinck E.H.,van Assen S.,Bierman W.F.W.,Koopmans P.P.,Keuter M.,van der Ven A.J.A.M.,ter Hofstede H.J.M.,Dofferhoff A.S.M.,Warris A.,van Crevel R.,Hoepelman A.I.M.,Mudrikova T.,Schneider M.M.E.,Ellerbroek P.M.,Oosterheert J.J.,Arends J.E.,Wassenberg M.W.M.,Barth R.E.,van Agtmael M.A.,Perenboom R.M.,Claessen F.A.P.,Bomers M.,Peters E.J.G.,Geelen S.P.M.,Wolfs T.F.W.,Bont L.J.,Richter C.,van der Berg J.P.,Gisolf E.H.,van den Berge M.,Stegeman A.,van Vonderen M.G.A.,van Houte D.P.F.,Weijer S.,el Moussaoui R.,Winkel C.,Muskiet F.,Voigt R.,Bonnet F.,Dabis F.,Bonnet F.,Bouchet S.,Breilh D.,Chêne G.,Dabis F.,Dupon M.,Fleury H.,Gaborieau V.,Lacoste D.,Malvy D.,Mercié P.,Morlat P.,Neau D.,Pellegrin I.,Pellegrin JL.,Reigadas S.,Tchamgoué S.,Bruyand M.,Chêne G.,Dabis F.,Fagard C.,Lawson-Ayayi S.,Richert L.,Thiébaut R.,Wittkop L.,André K.,Bonnet F.,Bernard N.,Caunègre L.,Cazanave C.,Ceccaldi J.,Chossat I.,Courtault C.,Dauchy F.A.,De Witte S.,Dondia D.,Dupon M.,Dupont A.,Duffau P.,Dutronc H.,Farbos S.,Faure I.,Gaborieau V.,Gerard Y.,Greib C.,Hessamfar-Joseph M.,Imbert Y.,Lacoste D.,Lataste P.,Lazaro E.,Malvy D.,Marie J.,Mechain M.,Meraud JP.,Mercié P.,Monlun E.,Morlat P.,Neau D.,Ochoa A.,Pellegrin J.L.,Pillot-Debelleix M.,Pistone T.,Raymond I.,Receveur M.C.,Rispal P.,Sorin L.,Tchamgoué S.,Valette C.,Vandenhende M.A.,Vareil MO.,Viallard J.F.,Wille H.,Wirth G.,Moreau J.F.,Pellegrin I.,Fleury H.,Lafon M.E.,Reigadas S.,Trimoulet P.,Bouchet S.,Breilh D.,Haramburu F.,Miremont-Salamé G.,Blaizeau M.J.,Crespel I.,Decoin M.,Delveaux S.,Diarra F.,D'Ivernois C.,Hanappier C.,Lacoste D.,Lawson-Ayayi S.,Leleux O.,Le Marec F.,Lenaud E.,Mourali J.,Pernot E.,Pougetoux A.,Uwamaliya-Nziyumvira B.,Tsaranazy A.,Valdes A.,Conte V.,Louis I.,Palmer G.,Sapparrart V.,Touchard D.,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 M.,Nolan D.,Skett J.,Calvo G.,Torres F.,Mateu S.,Domingo P.,Sambeat M.A.,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 A.F.,Gerard M.,Kabeya K.,Konopnicki D.,Libois A.,Martin C.,Payen M.C.,Semaille P.,Van Laethem Y.,Neaton J.,Bartsch G.,El-Sadr W.M.,Krum E.,Thompson G.,Wentworth D.,Luskin-Hawk R.,Telzak E.,El-Sadr W.M.,Abrams D.I.,Cohn D.,Markowitz N.,Arduino R.,Mushatt D.,Friedland G.,Perez G.,Tedaldi E.,Fisher E.,Gordin F.,Crane L.R.,Sampson J.,Baxter J.,Lundgren J.,Kirk O.,Mocroft A.,Cozzi-Lepri A.,Grint D.,Podlekareva D.,Kjær J.,Peters L.,Reekie J.,Kowalska J.,Tverland J.,Fischer A. H.,Nielsen J.,Elias C.,Vetter N.,Zangerle R.,Karpov I.,Vassilenko A.,Mitsura V.M.,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 A-B. E.,Skinhøj P.,Pedersen C.,Ostergaard L.,Zilmer K.,Ristola M.,Katlama C.,Viard J-P.,Girard P-M.,Livrozet J.M.,Vanhems P.,Pradier C.,Dabis F.,Neau D.,Rockstroh J.,Schmidt R.,van Lunzen J.,Degen O.,Stellbrink H.J.,Staszewski S.,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.,Maria S.,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.,Sacco L.,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.,Staneková D.,Tomazic J.,González-Lahoz J.,Soriano V.,Labarga P.,Medrano J.,Moreno S.,Rodriguez J.M.,Clotet B.,Jou A.,Paredes R.,Tural C.,Puig J.,Bravo I.,Gatell J.M.,Miró J.M.,Domingo P.,Gutierrez M.,Mateo G.,Sambeat M.A.,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 A.M.,Mercey D.,Phillips A.,Johnson M.A.,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.,Castelli F.,Cauda R.,Di Perri G.,Galli M.,Iardino R.,Ippolito G.,Lazzarin A.,Perno C.F.,von Schloesser F.,Viale P.,Antinori A.,Castagna A.,Ceccherini-Silberstein F.,Cozzi-Lepri A.,Girardi E.,Lo Caputo S.,Mussini C.,Puoti M.,Andreoni M.,Ammassari A.,Antinori 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.,Rusconi S.,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.,Minardi C.,Quirino T.,Abeli C.,Manconi P.E.,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 A. P.,Galli M.,Lazzarin A.,Rizzardini G.,Puoti M.,Ridolfo A.L.,Piolini R.,Castagna A.,Salpietro S.,Carenzi L.,Moioli M.C.,Cicconi P.,Marchetti G.,Mussini C.,Puzzolante C.,Gori A.,Lapadula G.,Abrescia N.,Chirianni A.,Guida M.G.,Onofrio M.,Baldelli F.,Francisci D.,Parruti G.,Ursini T.,Magnani G.,Ursitti M.A.,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 M.S.,Madeddu G.,Caramello P.,Di Perri G.,Orofino G.C.,Bonora S.,Sciandra M.,Pellizzer G.,Manfrin V.,Pradier C.,Fontas E.,Dollet K.,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 P.M.,Aubert V.,Battegay M.,Bernasconi E.,Böni J.,Bucher HC.,Burton-Jeangros C.,Calmy A.,Cavassini M.,Dollenmaier G.,Egger M.,Elzi L.,Fehr J.,Fellay J.,Furrer H.,Fux CA.,Gorgievski M.,Günthard H.,Haerry D.,Hasse B.,Hirsch HH.,Hoffmann M.,Hösli I.,Kahlert C.,Kaiser L.,Keiser O.,Klimkait T.,Kouyos R.,Kovari H.,Ledergerber B.,Martinetti G.,Martinez de Tejada B.,Metzner K.,Müller N.,Nadal D.,Nicca D.,Pantaleo G.,Rauch A.,Regenass S.,Rickenbach M.,Rudin C.,Schöni-Affolter F.,Schmid P.,Schüpbach J.,Speck R.,Tarr P.,Telenti A.,Trkola A.,Vernazza P.,Weber R.,Yerly S.,

Affiliation:

1. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Switzerland

2. Research Department of Infection and Population Health, University College London, United Kingdom

3. CHIP, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, København, Denmark

4. Division of Infectious Diseases and Department of Global Health, Academic Medical Center, University of Amsterdam, Netherlands

5. The Kirby Institute for Infection and Immunity in Society, University of New South Wales, Sydney, Australia

6. Department of Public Health, Nice University Hospital, France

7. Université Bordeaux, ISPED, Centre INSERM U897-Epidémiologie-Biostatistique France

8. Department of Health Sciences, San Paolo University Hospital, Milan, Italy

9. Department of Infectious Diseases, St. Pierre University Hospital, Brussels, Belgium

Abstract

Abstract Background. Although human immunodeficiency virus (HIV)-positive persons on antiretroviral therapy (ART) frequently have chronic liver enzyme elevation (cLEE), the underlying cause is often unclear. Methods. Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study participants without chronic viral hepatitis were observed to the earliest of cLEE (elevated aminotransferase ≥6 months), death, last follow-up, or January 2, 2014. Antiretroviral treatment exposure was categorized as follows: no exposure and ongoing short- and long-term exposure (<2 or ≥2 years) after initiation. Association between development of cLEE and ART exposure was investigated using Poisson regression. Results. Among 21 485 participants observed for 105 413 person-years (PY), 6368 developed cLEE (incidence 6.04/100 PY; 95% confidence interval [CI], 5.89–6.19). Chronic liver enzyme elevation was associated with short-and long-term exposure to didanosine (<2 years rate ratio [RR] = 1.29, 95% CI, 1.11–1.49; >2 years RR = 1.26, 95% CI, 1.13–1.41); stavudine (<2 years RR = 1.51, 95% CI, 1.26–1.81; >2 years RR = 1.17, 95% CI, 1.03–1.32), and tenofovir disoproxil fumarate (<2 years RR = 1.55, 95% CI, 1.40–1.72; >2 years RR = 1.18, 95% CI, 1.05–1.32), but only short-term exposure to nevirapine (<2 years RR = 1.44, 95% CI, 1.29–1.61), efavirenz (<2 years RR = 1.14, 95% CI, 1.03–1.26), emtricitabine (<2 years RR = 1.18, 95% CI, 1.04–1.33), and atazanavir (<2 years RR = 1.20, 95% CI, 1.04–1.38). Chronic liver enzyme elevation was not associated with use of lamivudine, abacavir, and other protease inhibitors. Mortality did not differ between participants with and without cLEE. Conclusions. Although didanosine, stavudine, nevirapine, and efavirenz have been described to be hepatotoxic, we additionally observed a consistent association between tenofovir and cLEE emerging within the first 2 years after drug initiation. This novel tenofovir-cLEE signal should be further investigated.

Funder

Highly Active Antiretroviral Therapy Oversight Committee

AbbVie, Bristol-Myers Squibb, Gilead Sciences Inc.

ViiV Healthcare

Merck & Co Inc.

Janssen Pharmaceuticals

Danish National Research Foundation

(

Dutch Ministry of Health, Welfare and Spor

Agence

Nationale de

Recherches sur le