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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serval:BIB_0B580C87B6D8
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Institution
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.
Journal
Journal of Antimicrobial Chemotherapy
Author(s)
Cozzi-Lepri A., Noguera-Julian M., Di Giallonardo F., Schuurman R., Däumer M., Aitken S., Ceccherini-Silberstein F., D'Arminio Monforte A., Geretti A.M., Booth C.L., Kaiser R., Michalik C., Jansen K., Masquelier B., Bellecave P., Kouyos R.D., Castro E., Furrer H., Schultze A., Günthard H.F., Brun-Vezinet F., Paredes R., Metzner K.J.
Working group(s)
CHAIN Minority HIV-1 Variants Working Group
Contributor(s)
Paredes R., Metzner KJ., Cozzi-Lepri A., Schuurman R., Brun-Vezinet F., Günthard H., Ceccherini-Silberstein F., Kaiser R., Geretti AM., Brockmeyer N., Masquelier B.
ISSN
1460-2091 (Electronic)
ISSN-L
0305-7453
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
70
Number
3
Pages
930-940
Language
english
Notes
Publication types: Journal Article Publication Status: ppublish
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 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.
Pubmed
Web of science
Open Access
Yes
Create date
10/04/2015 18:17
Last modification date
20/08/2019 12:33
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