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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ورودعنوان ژورنال:
دوره 70 شماره
صفحات -
تاریخ انتشار 2015