Open AccessAntiretroviral 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
Author(s) -
Helen Kovari,
Caroline Sabin,
Bruno Ledergerber,
Lene Ryom,
Peter Reiss,
Matthew Law,
Christian Pradier,
François Dabis,
Antonella d’Arminio Monforte,
Colette Smith,
Stéphane De Wit,
Ole Kirk,
Jens Lundgren,
Rainer Weber,
William G. Powderly,
N. Shortman,
Christiane Moecklinghoff,
G. Reilly,
Xavier Franquet,
Camilla I. Hatleberg,
Daniella Kamara,
A. Phillips,
Amanda Mocroft,
Anders Bojesen,
Jens Nielsen,
Charles E. Matthews,
David Raben,
Rikke Salbøl Brandt,
Martin Rickenbach,
Iuri Fanti,
Eric Krum,
M Hillebregt,
S. Geffard,
Jaohar Mourabi,
Anders Sundström,
M Delforge,
Éric Fontas,
Ferrán Torres,
Hamish McManus,
Seth Wright,
Jesper Kjær,
Anette Sjøl,
P. Meidahl,
J. Helweg-Larsen,
Johan Iversen,
Michael J. Ross,
Christoph A. Fux,
P. Morlat,
Olivier Moranne,
Anouk M Kesselring,
David A Kamara,
Nina FriisMøller,
Justyna D. Kowalska,
Mathias Bruyand,
Mark Bower,
Gerd Fätkenheuer,
Andrew E. Grulich,
S Zaheri,
Luuk Gras,
Jan M. Prins,
Taco W. Kuijpers,
H. J. Scherpbier,
Jan T. M. van der Meer,
F.W.M.N. Wit,
Mieke H. Godfried,
T. van der Poll,
F.J.B. Nellen,
J Lange,
Suzanne E. Geerlings,
M. van Vugt,
Dasja Pajkrt,
J. C. Bos,
Marc van der Valk,
Marlous L. Grijsen,
W. Joost Wiersinga,
Abraham Goorhuis,
Joppe W. Hovius,
S.H. Lowe,
Astrid Oude Lashof,
Dirk Posthouwer,
M.J.H. Pronk,
Heidi S. M. Ammerlaan,
M.E. van der Ende,
T.E.M.S. de Vries-Sluijs,
Carolina A. M. Schurink,
Jan Nouwen,
Annelies Verbon,
Bart Rijnders,
Eric C. M. Van Gorp,
M. van der Feltz,
Gertjan J. A. Driessen,
Annemarie M. C. van Rossum,
Judith Branger,
Emile F. Schippers,
Cees van Nieuwkoop,
E. P. van Elzakker,
P. H. P. Groeneveld,
J.W. Bouwhuis,
Robert Soetekouw,
Reinier W. ten Kate,
Frank P. Kroon,
Jaap T. van Dissel,
Sandra M. Arend,
Mark de Boer,
H. Jolink,
Hans Vollaard,
Martijn P. Bauer,
Jan G. den Hollander,
Katalin Pogány,
G. van Twillert,
W. Kortmann,
J. W. T. Cohen Stuart,
B. M. W. Diederen,
Eliane M.S. Leyten,
L. B. S. Gelinck,
G. J. Kootstra,
Corine E. Delsing,
K. Brinkman,
Willem L. Blok,
P. H. J. Frissen,
W.E.M. Schouten,
G.E.L. van den Berk,
M.E.E. van Kasteren,
A.E. Brouwer,
Jan A. Veenstra,
Kamilla D. Lettinga,
Jan W. Mulder,
S.M.E. Vrouenraets,
Fanny N. Lauw,
Arne van Eeden,
D. W. M. Verhagen,
Herman G. Sprenger,
R. A. Doedens,
Elisabeth H. Schölvinck,
Sander van Assen,
Wouter F.W. Bierman,
P.P. Koopmans,
Monique Keuter,
André van der Ven,
H.J.M. ter Hofstede,
A. S. M. Dofferhoff,
Adilia Warris,
Reinout van Crevel,
A. I. M. Hoepelman,
Tania Mudrikova,
Michael Schneider,
Pauline M. Ellerbroek,
Jan Jelrik Oosterheert,
J.E. Arends,
M.W.M. Wassenberg,
Roos E. Barth,
Michiel A. van Agtmael,
R.M. Perenboom,
Frans A.P. Claessen,
Marije K. Bomers,
Edgar J.G. Peters,
Sibyl P. M. Geelen,
Tom F.W. Wolfs,
Louis Bont,
Claudia Richter,
J.P. van der Berg,
Elisabeth H. Gisolf,
Maarten van den Berge,
Arjan Stegeman,
Marit G. A. van Vonderen,
D P F van Houte,
Sebastiaan Weijer,
Rachida el Moussaoui,
Chris Winkel,
Faj Muskiet,
Robin M. Voigt,
Fidéline Bonnet-Serrano,
S. Bouchet,
Dominique Breilh,
Geneviève Chêne,
M. Dupon,
H. Fleury,
Valérie Gaborieau,
D. Lacoste,
Denis Malvy,
P. Mercié,
D. Neau,
Isabelle Pellegrin,
JL Pellegrin,
Sandrine Reigadas,
S. Tchamgoué,
Catherine Fagard,
S. LawsonAyayi,
Laura Richert,
Rodolphe Thiébaut,
L. Wittkop,
Keila Magalhães André,
N. Bernard,
L. Caunègre,
C. Cazanave,
J. Ceccaldi,
I. Chossat,
C Courtault,
F. Dauchy,
S Witte,
D. Dondia,
A. Dupont,
P. Duffau,
H. Dutronc,
Sophie Farbos,
I. Faure,
Y Gérard,
C. Greib,
M. Hessamfar-Joseph,
Yoannis Imbert,
P. Lataste,
Estibaliz Lazaro,
J. Marie,
M. Méchain,
JP. Meraud,
É. Monlun,
Anthony Ochoa,
M. Pillot-Debelleix,
Thierry Pistone,
Iona Raymond,
M. C. Receveur,
P Rispal,
L. Sorin,
C Valette,
M.A. Vandenhende,
MO. Vareil,
JeanFrançois Viallard,
H. Wille,
Grégory J. Wirth,
J.F. Moreau,
M.E. Lafon,
Pascale Trimoulet,
Françoise Haramburu,
G. Miremont-Salamé,
M.J. Blaizeau,
I. Crespel,
M. Decoin,
Sandrine Delveaux,
F. Diarra,
C d'Ivernois,
C. Hanappier,
Olivier Leleux,
Fabien Le Marec,
E. Lenaud,
J. Mourali,
Eileen Pernot,
A. Pougetoux,
B. Uwamaliya-Nziyumvira,
A. Tsaranazy,
Ana M. Valdes,
V. Conte,
I. Louis,
Gary A. Palmer,
Vincent Sapparrart,
Dominique Touchard,
Kathy Petoumenos,
Courtney Bendall,
Richard D. Moore,
Simon Edwards,
Jennifer Hoy,
K. Watson,
Norm Roth,
James Nicholson,
Mark Bloch,
TV Franic,
David Baker,
R. Vale,
Andrew Carr,
David A. Cooper,
J. Chuah,
M. Ngieng,
David Nolan,
J. Skett,
G. Calvo,
S Mateu,
Peré Domingo,
Ma Antònia Sambeat,
Josep M. Gatell,
Elena del Cacho,
Josep Puig i Cadafalch,
M J García Fuster,
Carles Codina,
G. Sirera,
A. Vaqué,
Nathan Clumeck,
Coca Necsoi,
Anne-Françoise Gennotte,
Marcel Gérard,
Kenji Kabeya,
Déborah Konopnicki,
Agnès Libois,
Charlotte Martin,
M.C. Payen,
Pascal Semaille,
Yves Van Laethem,
J. Neaton,
Glenn E. Bartsch,
Wafaa ElSadr,
G. Thompson,
Deborah Wentworth,
Roberta LuskinHawk,
Edward E. Telzak,
Donald I. Abrams,
Danny M. Cohn,
Norman Markowitz,
Roberto C. Arduino,
David Mushatt,
G. Friedland,
George Perez,
Ellen Tedaldi,
Edward A. Fisher,
Fred M. Gordin,
Lawrence R. Crane,
John J. Sampson,
J Baxter,
Alessandro CozziLepri,
Daniel Grint,
Daria Podlekareva,
Lars Peters,
J. Reekie,
J. Tverland,
A. H. Fischer,
Christelle Elias,
N. Vetter,
Robert Zangerle,
Igor Karpov,
Anna Vassilenko,
В. М. Мицура,
O. Suetnov,
Robert Colebunders,
Linos Vandekerckhove,
Vesnadarjan Hadziosmanovic,
Kosta Kostov,
Josip Begovać,
Ladislav Machala,
David Jilich,
Dalibor Sedláček,
Gitte Kronborg,
Thomas Benfield,
MV Larsen,
Jan Gerstoft,
Terese L. Katzenstein,
A-B. E. Hansen,
Peter Skinhøj,
C. Pedersen,
Lars Østergaard,
Kai Zilmer,
Matti Ristola,
Christine Katlama,
Viard Jp,
P-M. Girard,
J. M. Livrozet,
Philippe Vanhems,
Jürgen K. Rockstroh,
R. Schmidt,
Jan van Lunzen,
Olaf Degen,
H. J. Stellbrink,
Schlomo Staszewski,
J. Kosmidis,
Panagiotis Gargalianos,
G. Xylomenos,
J. Perdios,
G. Panos,
A. Filandras,
E. Karabatsaki,
H Sambatakou,
Dénes Bánhegyi,
F Mulcahy,
Israel Yust,
Dan Turner,
Michael Burke,
S Pollack,
Gamal Hassoun,
Shlomo Maayan,
Stefano Vella,
Roberto Esposito,
I. Mazeu,
Cristina Mussini,
Claudio Arici,
R. Pristerà,
Francesco Mazzotta,
Andrea Gabbuti,
Sconfienza Luca Maria,
Vincenzo Vullo,
Miriam Lichtner,
Antonio Chirianni,
E. Montesarchio,
Miriam Gargiulo,
G. Antonucci,
A. Testa,
Pasquale Narciso,
Chrysoula Vlassi,
Mauro Zaccarelli,
Adriano Lazzarin,
Antonella Castagna,
Nicola Gianotti,
Massimo Galli,
Anna Lisa Ridolfo,
L. Sacco,
Baiba Rozentāle,
Indra Zeltiņa,
Saulius Chaplinskas,
R Hemmer,
Thérèse Staub,
Vidar Ormaasen,
A Mæland,
Johan N. Bruun,
Brygida Knysz,
Jacek Gąsiorowski,
Andrzéj Horban,
Elżbieta Bąkowska,
Anna Grzeszczuk,
Robert Flisiak,
Anna BorońKaczmarska,
M. Pynka,
Miłosz Parczewski,
Marek Beniowski,
E. Mularska,
H Trocha,
Elżbieta Jabłonowska,
Ewa Małolepsza,
Kamila Wójcik,
Francisco Antunes,
Manuela Doroana,
L. Caldeira,
Kamal Mansinho,
Fernando Maltêz,
Dan Duiculescu,
Aza Rakhmanova,
Natalia Zakharova,
S. A. Buzunova,
Djordje Jevtović,
M Mokrás,
D Staneková,
Janez Tomažič,
Juan GonzálezLahoz,
Vincent Soriano,
Pablo Labarga,
J. Medraño,
Santiago Moreno,
J.M. Rodriguez,
Bonaventura Clotet,
A. Jou,
Roger Paredes,
Cristina Tural,
Jordi Puig,
Isabel Bravo,
JM Miró,
M. Gutierrez,
Gràcia Mateo,
Anna Karlsson,
Leo Flamholc,
P Francioli,
Matthias Cavassini,
Bernard Hirschel,
E. Boffi,
Hansjakob Furrer,
Manuel Battegay,
Luigia Elzi,
Елена Николаевна Кравченко,
Nelly Chentsova,
В М Фролов,
Galyna A Kutsyna,
S. Servitskiy,
Максим Ігорович Краснов,
Samantha Barton,
Margaret Johnson,
D Mercey,
M. A. Johnson,
M. Murphy,
Jonathan Weber,
G Scullard,
M Fisher,
Clifford Leen,
Linda Morfeldt,
Gunilla Thulin,
Börje Åkerlund,
Kadri Koppel,
C. Håkangård,
M Moroni,
Gioacchino Angarano,
Andrea Antinori,
Orlando Armignacco,
Francesco Castelli,
Roberto Cauda,
Giovanni Di Perri,
Rosaria Iardino,
Giuseppe Ippolito,
Carlo Federico Perno,
F von Schloesser,
Pierluigi Viale,
Francesca CeccheriniSilberstein,
Enrico Girardi,
Sergio Lo Caputo,
Massimo Puoti,
Massimo Andreoni,
Adriana Ammassari,
Claudia Balotta,
Paolo Bonfanti,
Stefano Bonora,
Marco Borderi,
R. Capobianchi,
Antonella Cingolani,
Paola Cinque,
Andrea De Luca,
A. Di Biagio,
Andrea Gori,
Giovanni Guaraldi,
Giuseppe Lapadula,
Giordano Madeddu,
Franco Maggiolo,
Giulia Marchetti,
S Marcotullio,
Laura Monno,
Eugenia Quirós-Roldán,
Stefano Rusconi,
Paola Cicconi,
Tiziana Formenti,
Laura Galli,
Patrizia Lorenzini,
Andrea Giacometti,
Andrea Costantini,
Carmen Rita Santoro,
Claudia Suardi,
Elisa Vanino,
Gabriella Verucchi,
C Minardi,
Tiziana Quirino,
C Abeli,
Paolo Emilio Manconi,
P Piano,
Jacopo Vecchiet,
Katia Falasca,
L Sighinolfi,
Daniela Segala,
Giovanni Cassola,
G. Viscoli,
A. Alessandrini,
R Piscopo,
Giovanni Mazzarello,
Claudio Maria Mastroianni,
Valeria Belvisi,
Ilaria Caramma,
Giuliano Rizzardini,
R. Piolini,
Stefania Salpietro,
Laura Carenzi,
M C Moioli,
Cinzia Puzzolante,
N Abrescia,
Melania Guida,
Mirella Onofrio,
Franco Baldelli,
Daniela Francisci,
Giustino Parruti,
Tamara Ursini,
G. Magnani,
M A Ursitti,
A D’Avino,
L Gallo,
Emanuele Nicastri,
R Acinapura,
M Capozzi,
Raffaella Libertone,
Gianpiero Tebano,
Anna Maria Cattelan,
M.S. Mura,
P Caramello,
Giancarlo Orofino,
Mauro Sciandra,
G. Pellizzer,
Vinicio Manfrin,
K Dollet,
C Caissotti,
P. Dellamonica,
E Bernard,
Éric Cua,
F. De Salvador-Guillouët,
J. Durant,
Sara Ferrando,
V. Mondain-Miton,
A. Naqvi,
I. Perbost,
B Prouvost-Keller,
Sylvie Pillet,
Pellegrina Pugliese,
V. Rahelinirina,
P. Roger,
Vincent Aubert,
Enos Bernasconi,
Jürg Böni,
HC. Bucher,
Claudine BurtonJeangros,
Alexandra Calmy,
G Dollenmaier,
Matthias Egger,
Jan Fehr,
Jacques Fellay,
C. A. Fux,
Meri Gorgievski,
Huldrych F. Günthard,
David Haerry,
Barbara Hasse,
Hans H. Hirsch,
Matthias Hoffmann,
Irène Hösli,
Christian R. Kahlert,
Laurent Kaiser,
Olivia Keiser,
Thomas Klimkait,
R. Kouyos,
G Martinetti,
Begoña Martínez de Tejada,
Karin J. Metzner,
N Müller,
David Nadal,
Dunja Nicca,
G Pantaleo,
Andri Rauch,
Stephan Regenass,
Charles M. Rudin,
F. Schöni-Affolter,
Patrick Schmid,
Jörg Schüpbach,
Roberto F. Speck,
Philip Tarr,
A. Telenti,
Alexandra Trkola,
P Vernazza,
Sabine Yerly
Publication year - 2016
Publication title -
open forum infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.546
H-Index - 35
ISSN - 2328-8957
DOI - 10.1093/ofid/ofw009
Subject(s) - medicine , emtricitabine , nevirapine , didanosine , efavirenz , relative risk , stavudine , adverse effect , confidence interval , immunology , viral load , human immunodeficiency virus (hiv) , antiretroviral therapy
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.SCOPUS: ar.jinfo:eu-repo/semantics/publishe
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom