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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

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dc.contributor Universitat de Vic. Càtedra de la Sida i Malalties Relacionades
dc.contributor.author Cozzi-Lepri, Alessandro
dc.contributor.author Noguera-Julian, Marc
dc.contributor.author Di Giallonardo, Francesca
dc.contributor.author Schuurman, Rob
dc.contributor.author Daümer, Rob
dc.contributor.author Aitken, Sue
dc.contributor.author Ceccherini-Silberstein, Francesca
dc.contributor.author D'Arminio Monforte, Antonella
dc.contributor.author Geretti, Anna Maria
dc.contributor.author Booth, Clare L.
dc.contributor.author Kaiser, Rolf
dc.contributor.author Michalik, Claudia
dc.contributor.author Jansen, Klaus
dc.contributor.author Masquelier, Bernard
dc.contributor.author Bellecave, Pantxika
dc.contributor.author Kouyos, Roger D.
dc.contributor.author Castro, Erika
dc.contributor.author Furrer, Hansjakob
dc.contributor.author Schultze, Anna
dc.contributor.author Günthard, Huldrych F.
dc.contributor.author Brun-Vezinet, Francoise
dc.contributor.author Paredes, Roger
dc.contributor.author Metzner, Karin
dc.date.accessioned 2015-04-15T11:40:40Z
dc.date.available 2015-04-15T11:40:40Z
dc.date.created 2015
dc.date.issued 2015
dc.identifier.citation Cozzi-Lepri, A., Noguera-Julian, M., Di Giallonardo, F., Schuurman, R., Daeumer, M., Aitken, S., et al. (2015). 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. Journal of Antimicrobial Chemotherapy, 70(3), 930-940. ca_ES
dc.identifier.issn 1460-2091
dc.identifier.uri http://hdl.handle.net/10854/3989
dc.description.abstract 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 (OR¼2.75, 95% CI¼1.35–5.60, P¼0.005); similar associations were observed for at least one MV versus no NRTIMVs (OR¼2.27, 95% CI¼0.76–6.77, P¼0.140) and at least oneMV versus no NNRTIMVs (OR¼2.41, 95% CI¼1.12–5.18, P¼0.024). A dose–effect relationship between virological failure and mutational loadwas found. Conclusions: Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART. ca_ES
dc.format application/pdf
dc.format.extent 11 p. ca_ES
dc.language.iso eng ca_ES
dc.publisher Oxford University Press ca_ES
dc.rights Tots els drets reservats ca_ES
dc.rights (c) Oxford University Press
dc.subject.other Sida -- Tractament ca_ES
dc.subject.other VIH (Virus) ca_ES
dc.subject.other Antiretrovirals ca_ES
dc.title 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 ca_ES
dc.type info:eu-repo/semantics/article ca_ES
dc.identifier.doi https://doi.org/10.1093/jac/dku426
dc.relation.publisherversion http://jac.oxfordjournals.org/content/70/3/930.abstract
dc.rights.accesRights info:eu-repo/semantics/closedAccess ca_ES
dc.type.version info:eu-repo/publishedVersion ca_ES
dc.indexacio Indexat a WOS/JCR ca_ES
dc.indexacio Indexat a SCOPUS

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