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Marseille, France

Terrier B.,University Pierre and Marie Curie | Carrat F.,University Pierre and Marie Curie | Geri G.,University Pierre and Marie Curie | Piroth L.,University of Burgundy | And 4 more authors.
Journal of Hepatology | Year: 2011

Background & Aims: Recent findings in hepatitis C virus (HCV)-monoinfected patients have shown a correlation between low serum levels of 25-OH vitamin D3 [25(OH)D3 and severe liver fibrosis and low sustained virologic response to therapy. Data are lacking in HIV-HCV coinfected patients. Methods: One hundred and eighty nine HIV-HCV coinfected patients, who received ≥80% of interferon (IFN) plus ribavirin therapy, were analyzed for baseline serum 25(OH)D3 levels. Correlations between serum 25(OH)D3 levels, chronic hepatitis C features, HCV virologic response to antiviral therapy, and HIV infection characteristics were analyzed. Results: Mean serum 25(OH)D3 level was 18.5 ± 9.8 ng/ml, including 162 (85%) patients with level ≤30 ng/ml. Serum 25(OH)D3 levels were significantly correlated with the histological Metavir fibrosis score (r = -0.16; p = 0.027). Patients with severe fibrosis (Metavir F3/F4) had lower serum 25(OH)D3 levels compared to F2 and F1 patients (16.2 ± 10.0 vs. 18.9 ± 8.5 and 20.9 ± 11.1 ng/ml, respectively; p = 0.06). In multivariate analysis, low serum 25(OH)D levels were independently associated with severe liver fibrosis (p = 0.04) and cold season (p = 0.0002). Serum levels of 25(OH)D3 were also significantly correlated with liver fibrosis as assessed by FibroTest® (r = -0.22; p = 0.008) and serum α2-macroglobulin levels (r = -0.23; p = 0.006). In contrast, no correlation was found between 25(OH)D3 levels and HCV sustained virologic response to IFN-based therapy [OR 0.98 (0.95-1.01); p = 0.22. No association was found between 25(OH)D3 levels and markers of HIV-related immunodeficiency. Conclusions: In HIV-HCV coinfected patients, low serum 25(OH)D3 levels correlate with severe liver fibrosis. In contrast, serum 25(OH)D3 levels are not linked to HCV virologic response to therapy or severity of immunodeficiency. © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved. Source

Lebreton F.,Caen University Hospital Center | Depardieu F.,Institute Pasteur Paris | Bourdon N.,Caen University Hospital Center | Fines-Guyon M.,Caen University Hospital Center | And 5 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

Enterococcus faecium UCN71, isolated from a blood culture, was resistant to low levels of vancomycin (MIC, 16 μg/ml) but susceptible to teicoplanin (MIC, 0.5 μg/ml). No amplification was observed with primers specific for the previously described glycopeptide resistance ligase genes, but a PCR product corresponding to a gene called vanN was obtained using degenerate primers and was sequenced. The deduced VanN protein was related (65% identity) to the D-alanine:D-serine VanL ligase. The organization of the vanN gene cluster, determined using degenerate primers and by thermal asymmetric interlaced (TAIL)-PCR, was similar to that of the vanC operons. A single promoter upstream from the resistance operon was identified by rapid amplification of cDNA ends (RACE)-PCR. The presence of peptidoglycan precursors ending in D-serine and D,D-peptidase activities in the absence of vancomycin indicated constitutive expression of the resistance operon. VanN-type resistance was transferable by conjugation to E. faecium. This is the first report of transferable D-Ala-D-Ser-type resistance in E. faecium. Copyright © 2011, American Society for Microbiology. All Rights Reserved. Source

Maasoumy B.,Hannover Medical School | Cobb B.,Roche Molecular Systems | Bremer B.,Hannover Medical School | Luk K.,Roche Molecular Systems | And 5 more authors.
Alimentary Pharmacology and Therapeutics | Year: 2014

Background Early on-treatment virological response is one of the most important predictors for sustained virological response (SVR) to treatment of chronic hepatitis C virus (HCV) genotype 1 infection with triple therapy including HCV protease inhibitors (PI). Treatment duration (24 vs. 48 weeks) is based on HCV RNA results at weeks 4 and 12 of PI therapy when HCV RNA must be 'undetectable' to allow shorter therapy. Aim To analyse the reliability of HCV RNA measurements at key decision time points (weeks 4 and 12) and the predictive value of concordant or discordant assay results for SVR. Methods Weeks 4 and 12 samples of patients receiving telaprevir-containing triple therapy were initially tested with the AmpliPrep/COBAS-TaqMan-HCV-Test-v1.0 (limit of detection; LOD = 15IU/mL) and retested with the AmpliPrep/COBAS-TaqMan-HCV-Test- v2.0 (LOD = 15IU/mL) and the High-Pure/COBAS-TaqMan-HCV-Test-v2.0 (LOD = 20IU/mL). Results Concordance among the three test results in classifying samples as HCV RNA 'undetectable' or 'detectable' was only 55% at week 4, but 85% at week 12. Retesting of 'undetectable' week 4 samples with the respective other assays revealed positive HCV RNA results in 32-50%. In 30%, HCV RNA was 'undetectable' by all three tests at week 4 and all of these patients achieved SVR. In contrast, treatment failure occurred in 62% of patients with at least one 'detectable' result, including cases with one or two other 'undetectable' tests at week 4. Conclusions A single 'undetectable' HCV RNA result at week 4 is not always associated with achieving SVR. Repeated testing in difficult-to-treat patients may identify those at risk for treatment failure. © 2013 John Wiley & Sons Ltd. Source

Mohamed S.,Laboratoire Alphabio | Mohamed S.,French Institute of Health and Medical Research | Penaranda G.,Laboratoire Alphabio | Gonzalez D.,Advanced Biological Laboratories ABL | And 6 more authors.
AIDS | Year: 2014

Objective: Drug-resistance mutations are routinely detected using standard Sanger sequencing, which does not detect minor variants with a frequency below 20%. The impact of detecting minor variants generated by ultra-deep sequencing (UDS) on HIV drug-resistance interpretations has not yet been studied. Design: Fifty HIV-1 patients who experienced virological failure were included in this retrospective study. Methods: The HIV-1 UDS protocol allowed the detection and quantification of HIV-1 protease and reverse transcriptase variants related to genotypes A, B, C, F and G. DeepChek-HIV simplified drug-resistance interpretation software was used to compare Sanger sequencing and UDS. Results: The total time required for the UDS protocol was found to be approximately three times longer than Sanger sequencing with equivalent reagent costs. UDS detected all of the mutations found by population sequencing and identified additional resistance variants in all patients. An analysis of drug resistance revealed a total of 643 and 224 clinically relevant mutations by UDS and Sanger sequencing, respectively. Three resistance mutations with more than 20% prevalence were detected solely by UDS: A98S (23%), E138A (21%) and V179I (25%). A significant difference in the drugresistance interpretations for 19 antiretroviral drugs was observed between the UDS and Sanger sequencing methods. Y181C and T215Y were the most frequent mutations associated with interpretation differences. Conclusion: A combination of UDS and DeepChek software for the interpretation of drug resistance results would help clinicians provide suitable treatments. A cut-off of 1% allowed a better characterization of the viral population by identifying additional resistance mutations and improving the drug-resistance interpretation. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source

Potron A.,University Paris - Sud | Rondinaud E.,University Paris - Sud | Poirel L.,University Paris - Sud | Belmonte O.,CHR Felix Guyon | And 3 more authors.
International Journal of Antimicrobial Agents | Year: 2013

Three enterobacterial isolates (two Klebsiella pneumoniae and one Escherichia coli) were recovered from three patients transferred from India to France in 2011. All three isolates were resistant or of intermediate susceptibility to all β-lactams and of decreased susceptibility to carbapenems. These three isolates expressed a novel carbapenem-hydrolysing β-lactamase, OXA-232, differing from OXA-181 and OXA-48 by one and five amino acid substitutions, respectively. Compared with OXA-181, OXA-232 had a lower ability to hydrolyse carbapenems but conversely possessed higher hydrolytic activities against penicillins. The blaOXA-232 gene was located on a 6.1-kb ColE-type non-conjugative plasmid. © 2012 Elsevier B.V. and the International Society of Chemotherapy. Source

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