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 (University College London)
Noguera-Julian, Marc (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Di Giallonardo, Francesca (University Hospital Zurich (Suïssa))
Schuurman, Rob (Department of Virology. University Medical Centre, Utrecht)
Däumer, Martin (Institut für Immunologie und Genetik, Kaiserslautern, Germany)
Aitken, Sue (Department of Virology. University Medical Centre, Utrecht)
Ceccherini-Silberstein, Francesca (Department of Experimental Medicine and Surgery, University of Rome Tor Vergata)
D'Arminio Monforte, Antonella (Clinic of Infectious Diseases, 'San Paolo' Hospital)
Geretti, Anna Maria (Institute of Infection & Global Health, University of Liverpool)
Booth, Clare L. (Department of Virology, Royal Free London NHS Foundation Trust)
Kaiser, Rolf (Institute of Virology, University of Cologne)
Michalik, Claudia (Competence Network for HIV/AIDS, Bochum, Germany)
Jansen, Klaus (Competence Network for HIV/AIDS, Bochum, Germany)
Masquelier, Bernard (Université Bordeaux 2)
Bellecave, Pantxika (Université Bordeaux 2)
Kouyos, Roger D. (University Hospital Zurich (Suïssa))
Castro, Erika (Centre Hospitalier Universitaire Vaudois (Lausanne, Suïssa). Service of Community Psychiatry)
Furrer, Hansjakob (Bern University Hospital)
Schultze, Anna (University College London)
Günthard, Huldrych F. (University Hospital Zurich (Suïssa))
Brun-Vezinet, Francoise (Department of Virology, Bichat University Hospital, Paris)
Paredes, Roger (Institut Germans Trias i Pujol. Institut de Recerca de la Sida IrsiCaixa)
Metzner, Karin J. (University Hospital Zurich (Suïssa))
CHAIN Minority HIV-1 Variants Working Group

Data:	2014
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Minority drug-resistant HIV-1 variants ; CHAIN ; Antiretroviral therapy ; European multicentre study
Publicat a:	Journal of antimicrobial chemotherapy, Vol. 70 (october 2014) , p. 930-940, ISSN 1460-2091

DOI: 10.1093/jac/dku426
PMID: 25336166

11 p, 354.4 KB

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