Cozzi-Lepri, Alessandro, Noguera-Julian, Marc ORCID: 0000-0002-6194-1395, Di Giallonardo, Francesca ORCID: 0000-0002-8749-4095, Schuurman, Rob ORCID: 0000-0002-0060-9831, Daeumer, Martin, Aitken, Sue, Ceccherini-Silberstein, Francesca, Monforte, Antonella D'Arminio, Geretti, Anna Maria, Booth, Clare L., Kaiser, Rolf, Michalik, Claudia, Jansen, Klaus, Masquelier, Bernard, Bellecave, Pantxika, Kouyos, Roger D., Castro, Erika, Furrer, Hansjakob ORCID: 0000-0002-1375-3146, Schultze, Anna, Guenthard, Huldrych F., Brun-Vezinet, Francoise, Paredes, Roger and Metzner, Karin J. (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. J. Antimicrob. Chemother., 70 (3). S. 930 - 941. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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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 (OR = 2.75, 95% CI = 1.35-5.60, P = 0.005); similar associations were observed for at least one MV versus no NRTIMVs (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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Cozzi-Lepri, AlessandroUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Noguera-Julian, MarcUNSPECIFIEDorcid.org/0000-0002-6194-1395UNSPECIFIED
Di Giallonardo, FrancescaUNSPECIFIEDorcid.org/0000-0002-8749-4095UNSPECIFIED
Schuurman, RobUNSPECIFIEDorcid.org/0000-0002-0060-9831UNSPECIFIED
Daeumer, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Aitken, SueUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ceccherini-Silberstein, FrancescaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Monforte, Antonella D'ArminioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Geretti, Anna MariaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Booth, Clare L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiser, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michalik, ClaudiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jansen, KlausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Masquelier, BernardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bellecave, PantxikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kouyos, Roger D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Castro, ErikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Furrer, HansjakobUNSPECIFIEDorcid.org/0000-0002-1375-3146UNSPECIFIED
Schultze, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Guenthard, Huldrych F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brun-Vezinet, FrancoiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Paredes, RogerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Metzner, Karin J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-411790
DOI: 10.1093/jac/dku426
Journal or Publication Title: J. Antimicrob. Chemother.
Volume: 70
Number: 3
Page Range: S. 930 - 941
Date: 2015
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2091
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; ANTIRETROVIRAL TREATMENT; BASIC CONCEPTS; MUTATIONS; EFAVIRENZ; VARIANTS; THERAPY; POLYMORPHISMS; NEVIRAPINEMultiple languages
Infectious Diseases; Microbiology; Pharmacology & PharmacyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/41179

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