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Jordan J.A.,George Washington University | Plantier J.C.,Institute Of Biologie Clinique | Templeton K.,Royal Infirmary | Wu A.H.B.,San Francisco General Hospital
Journal of Clinical Virology | Year: 2016

Background: The most important reason for measuring HIV-1 viral load (VL) is to monitor the effectiveness of antiretroviral therapy (ART), both for the initial therapeutic response and sustained responses. Maintaining low or undetectable HIV-1 VL levels can reduce both the risks of progression to AIDS and transmission of infection to others. Objectives: To evaluate the diagnostic accuracy of Xpert® HIV-1 Viral Load (VL) assay compared to the Abbott RealTime HIV-1 assay, including assessing specificity by testing plasma specimens from confirmed HIV-1 negative blood donors. Study design: Subjects were enrolled from 4 participating sites, 2 in Europe and 2 in the USA. Fresh plasma samples were tested prospectively, while frozen plasma samples were collected prospectively, and tested retrospectively after selection of specimens to cover the assay's quantification range (40 cp/mL-10,000,000 cp/mL). Eligibility criteria included a clinician ordered HIV-1 VL test from a confirmed HIV-1 positive adult (≥18 years) with a known antiviral treatment status. Exclusion criteria included previous enrollment in this study or improper specimen collection. Human blood donor specimens determined to be HIV-1 negative by standard blood bank antibody and nucleic acid amplification methods were used to assess specificity. Results: Of the 764 specimens collected, 752 were eligible for inclusion but 5 were not tested by the Xpert, leaving 747 specimens tested (28.2% from females and 71.8% from males). Valid results were obtained for 724/747 (96.9%) specimens tested using the Xpert HIV-1 VL assay. The Xpert HIV-1 VL assay detected or quantified 568/724 (78.5%) specimens, while the RealTime HIV-1 assay detected or quantified 559/724 (77.2%). Of the 724 specimens tested by both assays, 390 were quantified by both assays and showed strong correlation: r = 0.9847, with an R2 = 0.9696. Bland-Altman analysis showed good agreement between the two assays (381/390; 97.7%) with a distribution within 0.5 log10 cp/mL centered around zero. Xpert yielded VLs for 393 (80%) of the 494 quantifiable samples by Abbott. VLs of those specimens quantified by one of the assays, and either detected but not quantified or not detected by the other assay were all <170 cp/mL. Specificity of the Xpert assay was found to be 100% (109/109), 95% CI: 96.7-100.0. Conclusion: Very good correlation was seen between the Xpert HIV-1 VL and Abbott RealTime HIV-1 assays, with added benefits for Xpert HIV-1 VL of: (1) lot-to-lot consistency traceable to WHO International Standard, (2) requiring both high and low level internal controls to be in range to have a valid result, (3) use of a single HIV-1 target for PCR and (4) faster turn-around-time for results, no need to wait to do batch testing of specimens. In summary, Xpert HIV-1 VL generated accurate VL results that if implemented could allow for actionable and timely treatment decisions during the same clinic visit. This scenario could reduce the loss to follow up often seen when these test results take days to weeks to become available to the clinician and patient. © 2016. Source


Caffeine, the main alkaloid in coffee, corresponds to the 1-3-7 trimethylxanthine. Its concentration is lower in tea and chocolate, where it is associated with theophylline, 1-3 dimethylxanthine, in tea and with theobromine, 3-7 dimethylxanthine, in chocolate. Paraxanthine, 1-7dimethylxanthine, for its part, is produced by the hepatic metabolism of caffeine operated by a cytochrome of 1A2 type. The effects of these methylxanthines on awaking, anxiety, neuroprotection in Alzheimer's and Parkinson's diseases, mood, schizophrenia and nociception are briefly considered. This review is concluded by indicating that these effects of methylxanthines may be modified by various associated substances, such as polyphenols displaying antioxydant properties. © 2010 Springer Verlag France. Source


Javot L.,Nancy University Hospital Center | Tala S.,Nancy University Hospital Center | Scala-Bertola J.,Nancy University Hospital Center | Massy N.,Institute Of Biologie Clinique | And 5 more authors.
Therapie | Year: 2011

Objectives. To identify and characterize the observations of sarcoidosis occurring during anti-TNF blockade collected in the French Pharmacovigilance system database and reported in the literature. Results. Seven cases were reported in the French Pharmacovigilance system database and 39 cases (37 original) have been reported internationally. Monoclonal antibodies (infliximab and adalimumab) and fusion protein (etanercept) are equally involved. Sarcoidosis have been confirmed histologically and occurred predominantly in the rheumatoid arthritis (22) and spondylarthropathy (16). Conclusion. The lack of protopathic bias suggests that these paradoxical sarcoidosis occurring during treatment with anti-TNF are a class-effect, as with psoriasis, uveitis, and IBD reported under similar conditions. Their pathogenesis remains unclear. © 2011 Société Francaise de Pharmacologie et de Thé rapeutique. Source


Leoz M.,CNR Institute of Neuroscience | Leoz M.,University of Rouen | Chaix M.-L.,University of Paris Descartes | Delaugerre C.,Laboratoire Of Virologie | And 7 more authors.
AIDS | Year: 2011

Background: HIV-1 group M is characterized by substantial genetic diversity, and includes nine subtypes, more than 45 circulating recombinant forms (CRFs), and numerous unique recombinant forms (URFs). In France, the epidemic is characterized by predominance of subtype B strains, increasing prevalence of non-B subtypes (CRF02-AG being the most prevalent) and increasing at-risk behaviour in the MSM population. The high prevalence and co-circulation of B and CRF02-AG strains in this population raise the possibility that recombinant forms might emerge and spread. Methods: Samples from seven patients (five being MSM) were selected on the basis of subtyping discordances in different regions. The pattern of each near full-length genome of the viruses was characterized. The relationships between the newly and previously described B/CRF02-AG URFs were analysed using phylogenetic networks. Single genome amplification was used to search for the parental strains and confirmation of the breakpoints. Results: Seven unique recombination patterns were identified, breakpoints being found throughout the genomes, with hotspots in pol and accessory genes. No link was observed with the previous forms, but the CRF02 regions of two new viruses indicated that they are phylogenetically associated, suggesting a common ancestral strain. No evidence of circulating parental strains was found. Conclusion: This description of seven URFs involving subtype B and CRF02-AG highlights the growing complexity of HIV molecular epidemiology in France. These multiple patterns, found mostly in MSM, and the hypothesis of a better fitness of some recombinant strains, argue for a context that could lead to the genesis of CRFB/02-AG strains in France. © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins. Source


Schneider P.,University of Rouen | Van Dreden P.,Roche Holding AG | Rousseau A.,Roche Holding AG | Marie-Cardine A.,University of Rouen | And 4 more authors.
Thrombosis Research | Year: 2011

Background: Complications of bone marrow transplantation (BMT) are usually considered to be related to the secretion of inflammatory cytokines, which generate membrane microparticles rich in procoagulant phospholipids (PPL) from different cellular origins and release of endothelial proteins such as thrombomodulin (TM). The use of soluble TM quantified by ELISA (TM:Ag) as a marker of endothelial injury is complex in children since it is age-dependent. Materials and methods: Using a functional assay which quantifies the activity of sTM activity (TMa), we performed a pilot study to analyze the ratio TMa/TM:Ag in a control group of 25 healthy children, 8 children with autologous and 16 children with allogeneic BMT. In this last group, 8 experienced BMT complications. In addition, we used a functional assay which quantifies PPL. Results: In healthy children the ratio TMa/TM:Ag was independent of age and stable in children with a favorable outcome but significantly (p < 0.05) reduced by the use of antithymocyte globulin during the conditioning regimen, and regularly decreased in children with BMT complications. Surprisingly, low plasma PPL levels were associated with a poor outcome. Conclusion: The ratio TMa/TM:Ag could constitute a marker of endothelium injury, and its follow-up could be of interest for an early discrimination of children with high risk of complications during allogeneic BMT. The decrease of PPL could be also another marker of a poor evolution and deserves further investigations. © 2011 Elsevier Ltd. Source

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