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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

Cozzi-Lepri, Alessandro ; Noguera-Julian, Marc ; Di Giallonardo, Francesca ; Schuurman, Rob ; Däumer, Martin ; Aitken, Sue ; Ceccherini-Silberstein, Francesca ; D'Arminio Monforte, Antonella ; Geretti, Anna Maria ; Booth, Clare L ; Kaiser, Rolf ; Michalik, Claudia ; Jansen, Klaus ; Masquelier, Bernard ; Bellecave, Pantxika ; Kouyos, Roger D ; Castro, Erika ; Furrer, Hansjakob ; Schultze, Anna ; Günthard, Huldrych F ; Brun-Vezinet, Francoise ; Paredes, Roger ; Metzner, Karin J

Journal of antimicrobial chemotherapy, 2015-03, Vol.70 (3), p.930-940 [Periódico revisado por pares]

England: Oxford Publishing Limited (England)

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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
Autor: Cozzi-Lepri, Alessandro ; Noguera-Julian, Marc ; Di Giallonardo, Francesca ; Schuurman, Rob ; Däumer, Martin ; Aitken, Sue ; Ceccherini-Silberstein, Francesca ; D'Arminio Monforte, Antonella ; Geretti, Anna Maria ; Booth, Clare L ; Kaiser, Rolf ; Michalik, Claudia ; Jansen, Klaus ; Masquelier, Bernard ; Bellecave, Pantxika ; Kouyos, Roger D ; Castro, Erika ; Furrer, Hansjakob ; Schultze, Anna ; Günthard, Huldrych F ; Brun-Vezinet, Francoise ; Paredes, Roger ; Metzner, Karin J
Assuntos: Adult ; Antiretroviral drugs ; Antiretroviral Therapy, Highly Active - methods ; Case-Control Studies ; Cohort Studies ; Computational Biology ; Drug resistance ; Drug Resistance, Viral ; Europe ; Female ; Genotype ; High-Throughput Nucleotide Sequencing ; HIV ; HIV Infections - drug therapy ; HIV Infections - virology ; HIV-1 - drug effects ; HIV-1 - genetics ; HIV-1 - isolation & purification ; Human immunodeficiency virus ; Humans ; Male ; Original Research ; Regression analysis ; Reverse Transcriptase Inhibitors - therapeutic use ; Risk Assessment ; Sequence Analysis, DNA ; Treatment Failure ; Young Adult
É parte de: Journal of antimicrobial chemotherapy, 2015-03, Vol.70 (3), p.930-940
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
A.C.-L. and M. N.-J. contributed equally to this work, as did R. P. and K. J. M.
Members are listed in the Acknowledgements section.
Descrição: It is still debated if pre-existing minority drug-resistant HIV-1 variants (MVs) affect the virological outcomes of first-line NNRTI-containing ART. 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. 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. Pre-existing MVs more than double the risk of virological failure to first-line NNRTI-based ART.
Editor: England: Oxford Publishing Limited (England)
Idioma: Inglês

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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

England: Oxford Publishing Limited (England)

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