Low-frequency drug-resistant HIV-1 and risk of virological failure to first-line NNRTI-based ART: a multicohort European case–control study using centralized ultrasensitive 454 pyrosequencing

نویسندگان

  • Alessandro Cozzi-Lepri
  • Marc Noguera-Julian
  • Francesca Di Giallonardo
  • Rob Schuurman
  • Martin Däumer
  • Sue Aitken
  • Francesca Ceccherini-Silberstein
  • Antonella D'Arminio Monforte
  • Anna Maria Geretti
  • Clare L. Booth
  • Rolf Kaiser
  • Claudia Michalik
  • Klaus Jansen
  • Bernard Masquelier
  • Pantxika Bellecave
  • Roger D. Kouyos
  • Erika Castro
  • Hansjakob Furrer
  • Anna Schultze
  • Huldrych F. Günthard
  • Francoise Brun-Vezinet
  • Roger Paredes
  • Karin J. Metzner
  • Roger Paredes
  • Karin J. Metzner
  • Alessandro Cozzi-Lepri
  • Rob Schuurman
  • Francoise Brun-Vezinet
  • Huldrych Günthard
  • Francesca Ceccherini-Silberstein
  • Rolf Kaiser
  • Anna Maria Geretti
  • Norbert Brockmeyer
  • Bernard Masquelier
  • F. Dabis
  • M. Bruyand
  • G. Chêne
  • S. Lawson-Ayayi
  • R. Thiébaut
  • L. Wittkop
  • K. André
  • F. Bonnal
  • F. Bonnet
  • N. Bernard
  • L. Caunègre
  • C. Cazanave
  • J. Ceccaldi
  • I. Chossat
  • K. Courtaud
  • F. A. Dauchy
  • S. De Witte
  • M. Dupon
  • A. Dupont
  • P. Duffau
  • H. Dutronc
  • S. Farbos
  • V. Gaborieau
  • M. C. Gemain
  • Y. Gerard
  • C. Greib
  • M. Hessamfar
  • D. Lacoste
  • P. Lataste
  • E. Lazaro
  • M. Longy-Boursier
  • D. Malvy
  • J. P. Meraud
  • P. Mercié
  • E. Monlun
  • P. Morlat
  • D. Neau
  • A. Ochoa
  • J. L. Pellegrin
  • T. Pistone
  • M. C. Receveur
  • J. Roger Schmeltz
  • S. Tchamgoué
  • M. A. Vandenhende
  • M.O. Vareil
  • J. F. Viallard
  • J. F. Moreau
  • I. Pellegrin
  • H. Fleury
  • M. E. Lafon
  • B. Masquelier
  • S. Reigadas
  • P. Trimoulet
  • S. Bouchet
  • D. Breilh
  • M. Molimard
  • K. Titier
  • F. Haramburu
  • G. Miremont-Salamé.
  • M. J. Blaizeau
  • M. Decoin
  • J. Delaune
  • S. Delveaux
  • C. D'Ivernois
  • C. Hanapier
  • O. Leleux
  • E. Lenaud
  • B. Uwamaliya-Nziyumvira
  • X. Sicard
  • S. Geffard
  • F. Le Marec
  • V. Conte
  • A. Frosch
  • J. Leray
  • G. Palmer
  • D. Touchard
  • M. Losso
  • M. Kundro
  • J. M. Ramos Mejia
  • N. Vetter
  • R. Zangerle
  • I. Karpov
  • A. Vassilenko
  • V. M. Mitsura
  • O. Suetnov
  • N. Clumeck
  • S. De Wit
  • M. Delforge
  • E. Florence
  • L. Vandekerckhove
  • V. Hadziosmanovic
  • K. Kostov
  • J. Begovac
  • L. Machala
  • D. Jilich
  • D. Sedlacek
  • J. Nielsen
  • G. Kronborg
  • T. Benfield
  • M. Larsen
  • J. Gerstoft
  • T. Katzenstein
  • A.-B. E. Hansen
  • P. Skinhøj
  • C. Pedersen
  • L. Ostergaard
  • U. B. Dragsted
  • L. N. Nielsen
  • K. Zilmer
  • Jelena Smidt
  • M. Ristola
  • C. Katlama
  • J. P. Viard
  • P. M. Girard
  • P. Vanhems
  • C. Pradier
  • C. Duvivier
  • J. Rockstroh
  • R. Schmidt
  • J. van Lunzen
  • O. Degen
  • H. J. Stellbrink
  • M. Bickel
  • J. Bogner
  • G. Fätkenheuer
  • J. Kosmidis
  • P. Gargalianos
  • G. Xylomenos
  • J. Perdios
  • H. Sambatakou
  • D. Banhegyi
  • M. Gottfredsson
  • F. Mulcahy
  • I. Yust
  • D. Turner
  • M. Burke
  • S. Pollack
  • G. HassounRambam
  • H. Elinav
  • M. HaouziHadassah
  • R. EspositoI
  • F. Mazzotta
  • V. Vullo
  • M. Moroni
  • M. Andreoni
  • G. Angarano
  • A. Antinori
  • 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. Castagna
  • F. Ceccherini-Silberstein
  • A. Cozzi-Lepri
  • E. Girardi
  • S. Lo Caputo
  • C. Mussini
  • M. Puoti
  • A. Ammassari
  • C. Balotta
  • P. Bonfanti
  • S. Bonora
  • M. Borderi
  • M. R. Capobianchi
  • A. Cingolani
  • P. Cinque
  • A. De Luca
  • A. Di Biagio
  • N. Gianotti
  • A. Gori
  • G. Guaraldi
  • G. Lapadula
  • M. Lichtner
  • G. Madeddu
  • F. Maggiolo
  • G. Marchetti
  • S. Marcotullio
  • L. Monno
  • E. Quiros Roldan
  • S. Rusconi
  • P. Cicconi
  • I. Fanti
  • T. Formenti
  • L. Galli
  • P. Lorenzini
  • F. Carletti
  • S. Carrara
  • A. Castrogiovanni
  • A. Di Caro
  • F. Petrone
  • G. Prota
  • S. Quartu
  • A. Giacometti
  • A. Costantini
  • S. Mazzoccato
  • C. Santoro
  • C. Suardi
  • E. Vanino
  • G. Verucchi
  • C. Minardi
  • T. Quirino
  • C. Abeli
  • P. E. Manconi
  • P. Piano
  • J. Vecchiet
  • K. Falasca
  • L. Sighinolfi
  • D. Segala
  • G. Cassola
  • C. Viscoli
  • A. Alessandrini
  • R. Piscopo
  • G. Mazzarello
  • C. Mastroianni
  • V. Belvisi
  • I. Caramma
  • A. Chiodera
  • A. P. Castelli
  • G. Rizzardini
  • A. D'Arminio Monforte
  • A. L. Ridolfo
  • R. Piolini
  • S. Salpietro
  • L. Carenzi
  • M. C. Moioli
  • C. Tincati
  • C. Puzzolante
  • N. Abrescia
  • A. Chirianni
  • M. G. Guida
  • M. Gargiulo
  • F. Baldelli
  • D. Francisci
  • G. Parruti
  • T. Ursini
  • G. Magnani
  • M. A. Ursitti
  • A. d'Avino
  • L. Gallo
  • E. Nicastri
  • R. Acinapura
  • M. Capozzi
  • R. Libertone
  • G. Tebano
  • A. Cattelan
  • L. Sasset
  • M. S. Mura
  • B. Rossetti
  • P. Caramello
  • G. C. Orofino
  • M. Sciandra
  • M. Bassetti
  • A. Londero
  • G. Pellizzer
  • V. Manfrin
  • N. H. Brockmeyer
  • A. Skaletz-Rorowski
  • S. Dupke
  • A. Baumgarten
  • A. Carganico
  • S. Köppe
  • P. Kreckel
  • E. Lauenroth-Mai
  • M. Freiwald-Rausch
  • J. Gölz
  • A. Moll
  • M. Zeitz
  • M. Hower
  • S. Reuter
  • B. Jensen
  • T. Harrer
  • S. Esser
  • H. R. Brodt
  • A. Plettenberg
  • A. Stöhr
  • T. Buhk
  • M. Stoll
  • B. Kuhlmann
  • F. A. Mosthaf
  • A. Rieke
  • W. Becker
  • R. Volkert
  • H. Jäger
  • H. Hartl
  • A. Mutz
  • A. Ulmer
  • M. Müller
  • V. Aubert
  • J. Barth
  • M. Battegay
  • E. Bernasconi
  • J. Böni
  • H. C. Bucher
  • C. Burton-Jeangros
  • A. Calmy
  • M. Cavassini
  • M. Egger
  • L. Elzi
  • J. Fehr
  • J. Fellay
  • H. Furrer
  • C. A. Fux
  • M. Gorgievski
  • H. Günthard
  • D. Haerry
  • B. Hasse
  • H. H. Hirsch
  • I. Hösli
  • C. Kahlert
  • L. Kaiser
  • O. Keiser
  • T. Klimkait
  • H. Kovari
  • R. Kouyos
  • B. Ledergerber
  • G. Martinetti
  • B. Martinez de Tejada
  • K. Metzner
  • N. Müller
  • D. Nadal
  • G. Pantaleo
  • A. Rauch
  • S. Regenass
  • M. Rickenbach
  • C. Rudin
  • P. Schmid
  • D. Schultze
  • F. Schöni-Affolter
  • J. Schüpbach
  • R. Speck
  • C. Staehelin
  • P. Tarr
  • A. Telenti
  • A. Trkola
  • P. Vernazza
  • R. Weber
  • S. Yerly
چکیده

OBJECTIVES It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. METHODS This Europe-wide case-control study included ART-naive subjects infected with drug-susceptible HIV-1 as revealed by population sequencing, who achieved virological suppression on first-line ART including one NNRTI. Cases experienced virological failure and controls were subjects from the same cohort whose viraemia remained suppressed at a matched time since initiation of ART. Blinded, centralized 454 pyrosequencing with parallel bioinformatic analysis in two laboratories was used to identify MVs in the 1%-25% frequency range. ORs of virological failure according to MV detection were estimated by logistic regression. RESULTS Two hundred and sixty samples (76 cases and 184 controls), mostly subtype B (73.5%), were used for the analysis. Identical MVs were detected in the two laboratories. 31.6% of cases and 16.8% of controls harboured pre-existing MVs. Detection of at least one MV versus no MVs was associated with an increased risk of virological failure (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTI MVs (OR = 2.27, 95% CI = 0.76-6.77, P = 0.140) and at least one MV versus no NNRTI MVs (OR = 2.41, 95% CI = 1.12-5.18, P = 0.024). A dose-effect relationship between virological failure and mutational load was found. CONCLUSIONS Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.

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عنوان ژورنال:

دوره 70  شماره 

صفحات  -

تاریخ انتشار 2015