Laboratoire Alphabio

Marseille, France

Laboratoire Alphabio

Marseille, France

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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.


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.


Mohamed S.,Laboratoire Alphabio | Mohamed S.,French Institute of Health and Medical Research | Penaranda G.,Laboratoire Alphabio | Gonzalez D.,Advanced Biological Laboratories ABL | And 7 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.


Halfon P.,Hopital Ambroise Pare | Halfon P.,Laboratoire Alphabio | Benmoura D.,Hopital Ambroise Pare | Khiri H.,Laboratoire Alphabio | And 4 more authors.
Journal of Clinical Virology | Year: 2010

Background: HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 66 are considered carcinogenic for human beings. DNA-chip technology, Papillocheck® HPV-screening (Greiner) and reverse dot blot, Linear Array (LA) (Roche) are tools to assess the distribution of HPV genotypes. Objectives: The aim of the study was to compare the clinical performance of Papillocheck and LA assays using a clinical cut-off of CIN2+. The secondary aim was to comparatively assess the distribution of HPV types using these two assays. Study design: The study population comprised 239 women referred for colposcopy and histology. Papillocheck, LA, and Hybrid Capture II (HCII) tests were done on all samples. Results: All tests showed good sensitivity and NPV (greater than 90%). None of the comparisons of sensitivities, specificities, PPVs, and NPVs showed statistically relevant differences between tests. High-risk HPV positivity rate was similar for all tests (Papillocheck 75%, LA 77%, and HCII 73%). Agreement between tests was good. The concordance levels between HCII and Papillocheck and between HCII and LA were 93% (k = 0.82) and 92% (k = 0.80), respectively. Papillocheck and LA tests showed a high overall concordance rate of 96% (k = 0.90). HPV16 was the most detected type (45% with Papillocheck, and 47% with LA), and HPV31 was the second most detected type (13% with Papillocheck, and 14% with LA). Conclusions: The Papillocheck HPV-screening test and LA test have a good clinical sensitivity to detect HPV types in CIN2+ patients. These assays allow, in the same experiment, to detect and determine the virus type. Our study showed that HPV types 16 and 31/33 are the most prevalent. © 2009.


Maasoumy B.,Hannover Medical School | Cobb B.,Hoffmann-La Roche | Bremer B.,Hannover Medical School | Luk K.,Hoffmann-La Roche | 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.


Ouzan D.,Institute Arnault Tzanck | Penaranda G.,Laboratoire Alphabio | Joly H.,Institute Arnault Tzanck | Khiri H.,Laboratoire Alphabio | And 2 more authors.
Journal of Clinical Virology | Year: 2013

Background and objective: The aim of this study was to prospectively evaluate whether the addition of peg-IFN to a stable NA regimen leads to loss of HBsAg in HBeAg-negative patients with chronic hepatitis and HBV DNA fully suppressed by long-term NA treatment. Study design: We analyzed HBsAg levels in 10 HBsAg-positive, HBeAg-negative patients who received peg-IFN alpha-2a in addition to a NA regimen. Treatment lasted a maximum of 96 weeks, according to changes in the HBsAg titer. Before peg-IFN therapy, HBV DNA levels had been below the limit of detection for at least three years. Results: HBsAg levels declined in nine patients. Among these nine, four became HBsAg-negative after 48 weeks of peg-IFN treatment; these patients received peg-IFN for only 48 weeks. NAs were stopped in these four patients, and these levels remained stable for at least 18 months (loss of HBsAg; HBV-DNA negative). HBs seroconversion was observed in two patients. The remaining five patients received 96 weeks of peg-IFN therapy. One patient became HBsAg-negative at the end of peg-IFN therapy; another became HBsAg-negative six months later. Three patients did not become HBsAg-negative. NAs were stopped in the two patients who became HBsAg-negative with no relapse during 12 months of follow up. Conclusions: In HBsAg-positive, HBeAg-negative patients with HBV DNA were fully suppressed by long-term NA treatment, the addition of peg-INF for a maximum of 96 weeks based on HBsAg-titer monitoring led to a loss of HBsAg and cessation of NA therapy in six out of ten patients, with no relapse for 12-18 months of follow up. HBs seroconversion was observed in two patients. © 2013 Elsevier B.V.


Halfon P.,Laboratoire Alphabio | Benmoura D.,Hopital Ambroise Pare | Agostini A.,Hopital La Conception | Khiri H.,Laboratoire Alphabio | And 3 more authors.
Journal of Clinical Virology | Year: 2010

Background: DNA- and mRNA-based assays are the main tools used for detecting human papillomavirus (HPV) nucleic acid in clinical samples. A recent tool, NucliSENS EasyQ HPV, uses a new concept to directly detect the expression of HPV oncogenic factors (E6 and E7) from the most prevalent HPV genotypes in cervical cancer (16, 18, 31, 33 and 45). Objectives: The primary aim of the study is to assess the accuracy of NucliSENS EasyQ HPV in detecting high-risk (HR) HPV in a population of atypical cells of undetermined significance/low-grade squamous intraepithelial lesion/high-grade squamous lesion (ASCUS/LSIL/HSIL) patients using a clinical cut-off of a cervical dysplasia (CIN2+) histology. The secondary aim is to compare this mRNA-based assay with the DNA-based hybrid capture II (HCII) assay. Study design: The study population comprised 140 women referred for colposcopy and histology. NucliSENS EasyQ HPV test, hybrid capture II (HCII) test and linear array (LA) test were assessed on all samples. All the tests were performed on the samples collected in PreservCyt liquid media for liquid-based cytology (ThinPrep Pap test). Results: The clinical specificity of the NucliSENS EasyQ HPV was 63% for the detection of CIN2+ or HSIL patients, significantly higher than the specificity of HCII and LA (49% and 45%, respectively, p < 0.05). Agreement between HCII and NucliSENS EasyQ HPV was fair (k = 0.49) and was good between HCII and LA (k = 0.88). HPV 16 was the most-detected type (49% with NucliSENS EasyQ HPV and 56% with LA), and HPV 31 was the second most-detected HPV type (31% with NucliSENS EasyQ HPV and 29% with LA). Conclusions: The NucliSENS EasyQ HPV assay has interesting clinical sensitivity and specificity for the detection of HPV types in CIN2+ patients and shows comparable diagnostic values with the HCII DNA assay. This assay allows simultaneous detection of HPV mRNA and determination of the type of the main prevalent oncogenic virus. © 2009 Elsevier B.V. All rights reserved.


Halfon P.,Laboratoire Alphabio | Giorgetti C.,Institute Medical Of Reproduction | Khiri H.,Laboratoire Alphabio | Penaranda G.,Laboratoire Alphabio | And 3 more authors.
PLoS ONE | Year: 2010

Background: The risk of male-to-female intravaginal HIV-1 transmission is estimated at about 1 event per 200-2000 coital acts. The aim of this study was to assess the residual risk of HIV presence in semen in patients under HAART therapy. Methods and Findings: The study took place in France from October 2001 to March 2009. 394 paired blood and semen samples were provided from 332 HIV-1 infected men. The Roche Cobas AMPLICOR Monitor HIV assay was used to quantify HIV-1 RNA in blood and in seminal plasma. Three percent of 394 HIV-1 infected men enrolled in an assisted reproductive technology program harbored detectable HIV-1 RNA in semen, although they had no other sexually transmitted disease and their blood viral load was undetectable for at least 6 months under antiretroviral treatment. Conclusion: These data suggest that undetectable plasma HIV RNA means a lower risk of viral transmission through seminal fluid on a population level, but not necessarily at the level of the individual. © 2010 Halfon et al.


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.


Halfon P.,Laboratoire Alphabio | Berger P.,Institute Paoli Calmettes | Khiri H.,Laboratoire Alphabio | Martineau A.,Laboratoire Alphabio | And 3 more authors.
Journal of Medical Virology | Year: 2011

Preemptive therapy in hematopoietic cell transplantation is initiated by a diagnostic technique at first detection of cytomegalovirus (CMV). The aim of this study was to use the viral dynamics of CMV DNA viral to start preemptive therapy, and to prospectively compare the CMV viral load kinetics to pp65 antigenemia. Two hundred sixty-three blood samples were collected prospectively from 93 patients. All clinical decisions regarding use of preemptive therapy were based on CMV antigenemia. Based on the positivity of the antigen assay and clinical CMV outcome in allotransplant patients, an optimal threshold of 3.05log10 (1,130copies/ml) was found to discriminate patients who required preemptive therapy and those who did not (sensitivity, 71%; specificity, 65%). A DNAemia level increase of 2.24log10 (174copies/ml) per day was the optimal threshold to discriminate between patients who required preemptive therapy and those who did not (sensitivity, 93%; specificity, 43%). Sensitivity of PCR assay was 92.4% compared with 39% for the antigen assay (P<0.001). A standardized real-time PCR assay is more appropriate than the antigen assay for detecting CMV. It allowed earlier diagnosis of active CMV infection and monitoring of the response to anti-CMV treatment. J. Med. Virol. 83:490-495, 2011. © 2011 Wiley-Liss, Inc.

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