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157. In vitrostudies reveal that different modes of initiation on HIV-1 mRNA have different levels of requirement for eukaryotic initiation factor 4F

Author

Sylvain de Breyne, Mary-Anne Trabaud, Bruno Sargueil, Nathalie Chamond, Théophile Ohlmann, Didier Decimo, and Patrice Andre

Subjects
Genetics, 0303 health sciences, Five prime untranslated region, EIF4G, 030302 biochemistry & molecular biology, Cell Biology, Biology, Biochemistry, 3. Good health, 03 medical and health sciences, chemistry.chemical_compound, Eukaryotic initiation factor 4F, Internal ribosome entry site, Eukaryotic translation, chemistry, Eukaryotic initiation factor, Translational regulation, Initiation factor, Molecular Biology, 030304 developmental biology
Abstract

Expression of the two isoforms p55 and p40 of HIV-1 Gag proteins relies on distinct translation initiation mechanisms, a cap-dependent initiation and two internal ribosome entry sites (IRESs). The regulation of these processes is complex and remains poorly understood. This study was focused on the influence of the 5'-UTR and on the requirement for the eukaryotic initiation factor (eIF)4F complex components. By using an in vitro system, we showed substantial involvement of the 5'-UTR in the control of p55 expression. This highly structured 5'-UTR requires the eIF4F complex, especially RNA helicase eIF4A, which mediates initiation at the authentic AUG codon. In addition, the 5'-UTR regulates expression in an RNA concentration-dependent manner, with a high concentration of RNA triggering specific reduction of full-length Gag p55 production. HIV-1 genomic RNA also has the ability to use a strong IRES element located in the gag coding region. We show that this mechanism is particularly efficient, and that activity of this IRES is only poorly dependent on RNA helicase eIF4A when the viral 5'-UTR is removed. HIV-1 genomic mRNA exhibits in vitro translational features that allow the expression of Gag p55 protein by different mechanisms that involve different requirements for eIF4E, eIF4G, and eIF4A. This suggests that HIV-1 could adapt to its mode of translation according to the availability of the initiation factors in the infected cell.

Published
2012
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158. Different effects of the TAR structure on HIV-1 and HIV-2 genomic RNA translation

Author

Taran Limousin, Théophile Ohlmann, Ricardo Soto-Rifo, Didier Decimo, Emiliano P. Ricci, Olivier Moncorgé, Andrea Cimarelli, Mary-Anne Trabaud, Paulina S. Rubilar, Patrice Andre, Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunité infection vaccination (I2V), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospices Civils de Lyon (HCL), Université de Lyon, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Aptanomics, and CIMARELLI, Andrea

Subjects
Five prime untranslated region, [SDV]Life Sciences [q-bio], viruses, medicine.disease_cause, gag Gene Products, Human Immunodeficiency Virus, Ribosome, MESH: HIV-1, MESH: Proviruses, Proviruses, MESH: HIV-2, Protein biosynthesis, MESH: Animals, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Genetics, 0303 health sciences, MESH: HIV Long Terminal Repeat, 030302 biochemistry & molecular biology, MESH: gag Gene Products, Human Immunodeficiency Virus, 3. Good health, MESH: RNA, Viral, MESH: Protein Biosynthesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, MESH: 5' Untranslated Regions, MESH: Genome, Viral, HIV Long Terminal Repeat, Viral protein, Genome, Viral, Biology, Cell Line, 03 medical and health sciences, medicine, Animals, Humans, Post-transcriptional regulation, 030304 developmental biology, MESH: Humans, RNA, Virology, MESH: Cell Line, Viral replication, Protein Biosynthesis, HIV-2, HIV-1, 5' Untranslated Regions, Ribosomes, MESH: Ribosomes
Abstract

International audience; The 5′-untranslated region (5′-UTR) of the genomic RNA of human immunodeficiency viruses type-1 (HIV-1) and type-2 (HIV-2) is composed of highly structured RNA motifs essential for viral replication that are expected to interfere with Gag and Gag-Pol translation. Here, we have analyzed and compared the properties by which the viral 5′-UTR drives translation from the genomic RNA of both human immunodeficiency viruses. Our results showed that translation from the HIV-2 gRNA was very poor compared to that of HIV-1. This was rather due to the intrinsic structural motifs in their respective 5′-UTR without involvement of any viral protein. Further investigation pointed to a different role of TAR RNA, which was much inhibitory for HIV-2 translation. Altogether, these data highlight important structural and functional differences between these two human pathogens.

Published
2011
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159. Proficiency of transient elastography compared to liver biopsy for the assessment of fibrosis in HIV/HBV-coinfected patients

Author

J. Bottero, André Boibieux, Fabien Zoulim, Karine Lacombe, Laurent Cotte, M. Chevallier, Mary-Anne Trabaud, Patrick Miailhes, François Bailly, Pierre Pradat, and C. Trepo

Subjects
medicine.medical_specialty, Pathology, Cirrhosis, medicine.disease_cause, Gastroenterology, 03 medical and health sciences, Liver disease, 0302 clinical medicine, Fibrosis, Virology, Internal medicine, medicine, 030212 general & internal medicine, Hepatitis B virus, Hepatology, medicine.diagnostic_test, FibroTest, business.industry, medicine.disease, 3. Good health, Infectious Diseases, Liver biopsy, Coinfection, 030211 gastroenterology & hepatology, Transient elastography, business
Abstract

Transient elastography (TE) is a noninvasive technique to evaluate liver fibrosis. We compared the performance of TE with liver biopsy (LB) in patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection. Patients prospectively underwent TE and LB. The diagnosis accuracy of TE was calculated using receiver operating characteristic (ROC) curves for different stages of fibrosis, and optimal cut-off values were defined. A sequential algorithm combining TE with biochemical score (Fibrotest) is proposed. Fifty-seven patients had both TE and LB (median time: 3 days) and two with proven cirrhosis, only TE. Forty-six (78%) were under antiretroviral therapy with anti-HBV drugs in 98%, and 19 (32%) had elevated alanine aminotransferase (ALT). A significant correlation was observed between liver stiffness measurement (LSM) and METAVIR fibrosis stages (P < 0.0001). Patients with elevated ALT tended to have higher LSM than those with normal ALT. The areas under the ROC curves were 0.85 for significant fibrosis (≥ F2), 0.92 for advanced fibrosis (≥ F3) and 0.96 for cirrhosis. Using a cut-off of 5.9 kPa for F ≥ 2 and 7.6 kPa for F ≥ 3, the diagnosis accuracy was 83% and 86%, respectively. With an algorithm combining TE and Fibrotest, 97% of patients were well classified for significant fibrosis. Using this algorithm, the need for LB can be reduced by 67%. In HIV/HBV-coinfected patients, most of them with normal ALT under antiretroviral treatment including HBV active drugs, TE was proficient in discriminating moderate to severe fibrosis from minimal liver disease.

Published
2010
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160. Increasing prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-infected patients from 2001 to 2006/2007 in France

Author

Jacques Izopet, Jacqueline Cottalorda, Vincent Calvez, Charlotte Charpentier, Henia Saoudin, Georges Dos Santos, Mary-Anne Trabaud, Francis Barin, V. Calvez, Cécile Henquell, Delphine Desbois, C. Delaugerre, Slim Fourati, D. Bettinger, Thomas Bourlet, Anne Krivine, Bernard Masquelier, S. Vallet, M. Bouvier-Alias, Catherine Tamalet, B. Masquelier, S. Rogez, Coralie Pallier, J. C. Plantier, C. Charpentier, F. Barin, J. Cottalorda, A. Maillard, Alexandre Storto, G. DosSantos, Chakib Alloui, B. Montes, Marie-Laure Chaix, A. G. Marcelin, Anne Signori-Schmuck, D. Desbois, Anne-Geneviève Marcelin, Marie Laure Chaix, C. Tamalet, F. Brun-Vézinet, Françoise Brun-Vézinet, J. Izopet, Philippe Flandre, G. Anies, Anne Maillard, Diane Descamps, Patrice Andre, Jean-Claude Tardy, Dominique Costagliola, Brigitte Montes, Laurence Morand-Joubert, Annick Ruffault, Jean-Christophe Plantier, Sophie Pakianather, L. Morand-Joubert, and Constance Delaugerre

Subjects
Male, Microbiology (medical), Anti-HIV Agents, HIV Infections, Drug resistance, Nucleoside Reverse Transcriptase Inhibitor, 03 medical and health sciences, 0302 clinical medicine, HIV Protease, Drug Resistance, Viral, HIV Seropositivity, Prevalence, medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, Pharmacology, 0303 health sciences, Reverse-transcriptase inhibitor, biology, 030306 microbiology, Proteolytic enzymes, biology.organism_classification, Virology, HIV Reverse Transcriptase, Reverse transcriptase, 3. Good health, Infectious Diseases, Chronic Disease, Mutation, Immunology, Lentivirus, HIV-1, Reverse Transcriptase Inhibitors, Female, France, Viral disease, Viral load, medicine.drug
Abstract

Objectives: To estimate the prevalence of transmitted drug resistance mutations and non-B subtype circulation in antiretroviral-naive chronically HIV-1-infected patients in France. Methods: Resistance mutations were sought in samples from 530 newly diagnosed HIV-1-infected patients from October 2006 to March 2007. Protease and reverse transcriptase mutations were identified from the 2007 Stanford Resistance Surveillance list. Results: Reverse transcriptase and protease resistance mutations were determined in 466 patients with duration of seropositivity

Published
2010
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161. Evaluation of the Genotypic Prediction of HIV-1 Coreceptor Use versus a Phenotypic Assay and Correlation with the Virological Response to Maraviroc: the ANRS GenoTropism Study

Author

Recordon-Pinson, Patricia, Soulié, Cathia, Flandre, Philippe, Descamps, Diane, Lazrek, Mouna, Charpentier, Charlotte, Montes, Brigitte, Trabaud, Mary-Anne, Cottalorda, Jacqueline, Schneider, Véronique, Morand-Joubert, Laurence, Tamalet, Catherine, Desbois, Delphine, Macé, Muriel, Ferré, Virginie, Vabret, Astrid, Ruffault, Annick, Pallier, Coralie, Raymond, Stéphanie, Izopet, Jacques, Reynes, Jacques, Marcelin, Anne-Geneviève, Masquelier, Bernard, Renseigné, Non, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de microbiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Virology Laboratory, Hôpital Rothchild, Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Virology, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Human and Molecular Virology, Georges Clémenceau Universitary Hospital, Unité de Rétrovirologie, Hôpital Pontchaillou, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire de Virologie, Institut Fédératif de Biologie de Purpan, Variabilité génomique des virus, Université Bordeaux Segalen - Bordeaux 2-IFR66, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Microbiologie Fondamentale et Pathogénicité (MFP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)

Subjects
Male, Oncology, MESH: Sequence Analysis, DNA, Multivariate analysis, HIV Infections, HIV Envelope Protein gp120, MESH: Receptors, CCR5, Maraviroc, MESH: Genotype, MESH: HIV-1, Correlation, MESH: HIV Envelope Protein gp120, chemistry.chemical_compound, HIV Protease, HIV Fusion Inhibitors, Genotype, MESH: Receptors, HIV, Pharmacology (medical), MESH: Treatment Outcome, 0303 health sciences, MESH: Middle Aged, MESH: Tropism, MESH: HIV Infections, Middle Aged, MESH: Cyclohexanes, HIV Reverse Transcriptase, 3. Good health, Phenotype, Treatment Outcome, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, CCR5 Receptor Antagonists, Lentivirus, Female, Viral load, Adult, medicine.medical_specialty, Receptors, CCR5, MESH: HIV Reverse Transcriptase, Molecular Sequence Data, CCR5 receptor antagonist, Biology, MESH: Phenotype, Antiviral Agents, Sensitivity and Specificity, Tropism, MESH: HIV Protease, 03 medical and health sciences, Receptors, HIV, Cyclohexanes, Internal medicine, medicine, Humans, MESH: HIV Fusion Inhibitors, 030304 developmental biology, Pharmacology, MESH: Humans, MESH: Molecular Sequence Data, 030306 microbiology, MESH: Adult, Sequence Analysis, DNA, Triazoles, biology.organism_classification, Virology, MESH: Male, MESH: Sensitivity and Specificity, MESH: Triazoles, chemistry, Expanded access, HIV-1, MESH: Female
Abstract

Genotypic algorithms for prediction of HIV-1 coreceptor usage need to be evaluated in a clinical setting. We aimed at studying (i) the correlation of genotypic prediction of coreceptor use in comparison with a phenotypic assay and (ii) the relationship between genotypic prediction of coreceptor use at baseline and the virological response (VR) to a therapy including maraviroc (MVC). Antiretroviral-experienced patients were included in the MVC Expanded Access Program if they had an R5 screening result with Trofile (Monogram Biosciences). V3 loop sequences were determined at screening, and coreceptor use was predicted using 13 genotypic algorithms or combinations of algorithms. Genotypic predictions were compared to Trofile; dual or mixed (D/M) variants were considered as X4 variants. Both genotypic and phenotypic results were obtained for 189 patients at screening, with 54 isolates scored as X4 or D/M and 135 scored as R5 with Trofile. The highest sensitivity (59.3%) for detection of X4 was obtained with the Geno2pheno algorithm, with a false-positive rate set up at 10% (Geno2pheno10). In the 112 patients receiving MVC, a plasma viral RNA load of

Published
2010
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162. Factors Associated with Virological Response to Etravirine in Nonnucleoside Reverse Transcriptase Inhibitor-Experienced HIV-1-Infected Patients

Author

Charlotte Charpentier, Bernard Masquelier, Philippe Flandre, Dominique Bettinger, Cécile Henquell, Vincent Calvez, Annick Ruffault, Georges Dos Santos, Henia Saoudin, Sophie Vallet, Francis Barin, Jacques Izopet, Sylvie Rogez, Diane Descamps, Chakib Alloui, Catherine Tamalet, Anne Signori-Schmuck, Mary-Anne Trabaud, Jacqueline Cottalorda, Constance Delaugerre, Anne-Geneviève Marcelin, Magali Bouvier-Alias, and Laurence Morand-Joubert

Subjects
Male, Oncology, medicine.medical_specialty, Enfuvirtide, Genotype, Anti-HIV Agents, Etravirine, HIV Infections, Biology, Antiviral Agents, Nucleoside Reverse Transcriptase Inhibitor, 03 medical and health sciences, Interquartile range, Internal medicine, Drug Resistance, Viral, Nitriles, medicine, Humans, Pharmacology (medical), Phylogeny, Darunavir, 030304 developmental biology, Pharmacology, 0303 health sciences, Reverse-transcriptase inhibitor, Reverse Transcriptase Polymerase Chain Reaction, 030306 microbiology, virus diseases, Raltegravir, Virology, HIV Reverse Transcriptase, Reverse transcriptase, 3. Good health, Pyridazines, Pyrimidines, Treatment Outcome, Infectious Diseases, Mutation, HIV-1, RNA, Viral, Reverse Transcriptase Inhibitors, Female, medicine.drug
Abstract

To identify factors associated with virological response (VR) to an etravirine (ETR)-based regimen, 243 patients previously treated with nonnucleoside reverse transcriptase inhibitors (NNRTIs) were studied. The impact of baseline HIV-1 RNA, CD4 cell count, past NNRTIs used, 57 NNRTI resistance mutations, genotypic sensitivity score (GSS) for nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs), and the number of new drugs used with ETR for the first time on the VR to an ETR regimen were investigated. Among the 243 patients, the median baseline HIV-1 RNA level was 4.4 log10copies/ml (interquartile range [IQR], 3.7 to 4.9) and the median CD4 count was 175 cells/mm3(IQR, 69 to 312). Patients had been previously exposed to a median of 6 NRTIs, 1, NNRTI, and 5 PIs. Overall, 82% of patients achieved a VR at month 2, as defined by a decrease of at least 1.5 log10copies/ml and/or HIV-1 RNA level of

Published
2010
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163. Sexually transmitted HCV infection and reinfection in HIV-infected homosexual men

Author

I. Schlienger, Mary-Anne Trabaud, Laurent Cotte, Corinne Brochier, Fabien Zoulim, P. Chevallier Queyron, and Patrice Andre

Subjects
Male, Sexually transmitted disease, Sexual transmission, Genotype, HIV Infections, Interferon alpha-2, Antiviral Agents, Polyethylene Glycols, chemistry.chemical_compound, Acquired immunodeficiency syndrome (AIDS), Recurrence, Ribavirin, medicine, Humans, Homosexuality, Male, Risk factor, Unsafe Sex, business.industry, Gastroenterology, Interferon-alpha, virus diseases, General Medicine, Hepatitis C, medicine.disease, Virology, Recombinant Proteins, digestive system diseases, Serosorting, chemistry, Viral disease, business
Abstract

Summary Multiple, concomitant or successive hepatitis C virus (HCV) infections have been described in injection drug users and following organ transplantation and blood transfusion. However, data on sexual HCV reinfection is scarce. We report sexual HCV reinfection following viral eradication of a first HCV infection in two homosexual HIV-infected men. The first patient acquired HCV genotype 4 infection after resolution of an initial acute HCV genotype 1a infection. The second patient was infected with genotype 1a HCV following remission of an initial acute HCV genotype 4c/d infection. The two subjects were successfully treated with peginterferon alpha-2a and ribavirin for their first and second infection and achieved a sustained virological response on both occasions. Unprotected anal intercourse with multiple partners known to be HIV-positive (serosorting) was the only risk factor for HCV transmission reported by both patients. Therefore, sexual HCV reinfection can occur in homosexual men having unprotected sex and “serosorting” should be considered a risk factor for the sexual transmission of HCV.

Published
2009
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164. Investigations into the cross-reactivity of rabbit antibodies raised against nonhomologous pairs of synthetic peptides derived from HIV-1 gp120 proteins

Author

M. Sikorska-Walker, Velibor Krsmanovic, C. Desgranges, James F. Whitfield, M.-A. Trabaud, J.-M. Biquard, Milton T.W. Hearn, Jon P. Durkin, Irena Cosic, and Ammar Achour

Subjects
chemistry.chemical_classification, Protein family, Peptide, Cross Reactions, HIV Antibodies, HIV Envelope Protein gp120, Biology, Biochemistry, Epitope, Amino acid, chemistry.chemical_compound, Endocrinology, chemistry, Peptide synthesis, Animals, Humans, Rabbits, Peptides, Structural motif, Glycoprotein, Binding domain
Abstract

The immunological cross-reactivity of several peptides with specific pattern-property characteristics related to the epitopes of human immunodeficiency virus type 1 (HIV-1) gp160/ 120 envelope proteins has been investigated. Proteins with similar primary structures can be expected to show functional or topographic similarities, such as specific epitopes which may cross-react with antibodies derived from the immunisation of animals with other members of the same protein family. These structure-function characteristics may be revealed as periodicities derived from presentations based on the discrete Fourier transformation of the distributions of various physico-chemical amino acid descriptors, constituting the polypeptide backbone and amino acid side-chains of the protein molecule. Such approaches, for example, have permitted prediction of periodicities corresponding to secondary structural motifs, including amphipathic alpha-helices and beta-sheets, within protein sequences, and have helped to clarify potential binding sites for ligands, substrates or cofactors with interacting macromolecules. Based on this approach, characteristic periodicities have been identified which represent common Fourier transform spectral properties of the envelope (ENV) gp160/120 glycoproteins from a range of HIV-1 isolates. In addition, similar periodicities have been detected as components of the discrete Fourier transform representation of the corresponding amino acid descriptors of the CD4 binding domain of gp120. Accordingly, we have synthesised several peptides having periodic characteristics in their discrete Fourier transform representations similar to these HIV-1 proteins. These nonhomologous synthetic peptides induced cross-reactive antibodies in New Zealand White rabbits. Polyclonal antibodies raised to one of these peptides reacted with HIV-1 ENV gp120-related proteins, as determined by enzyme-linked immunosorbent assay and Western blotting techniques. These findings provide further evidence for a role of immunological cross-reactivity and molecular biomimicry in the development of peptide-based vaccines directed against viral or bacterial pathogens.

Published
2009
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165. Transactivation of the Hepatitis B Virus Core Promoter by the Nuclear Receptor FXRα

Author

Laure Perrin-Cocon, Olivier Diaz, Patrice Andre, Caroline Scholtes, Vincent Lotteau, C. Ramière, Vinca Icard, and Mary-Anne Trabaud

Subjects
Transcriptional Activation, Hepatitis B virus, Molecular Sequence Data, Immunology, Receptors, Cytoplasmic and Nuclear, Electrophoretic Mobility Shift Assay, Biology, medicine.disease_cause, Microbiology, Cell Line, Bile Acids and Salts, Transactivation, Genes, Reporter, Virology, Consensus Sequence, medicine, Humans, Luciferases, Promoter Regions, Genetic, Enhancer, Transcription factor, Repetitive Sequences, Nucleic Acid, Binding Sites, Retinoid X Receptor alpha, Base Sequence, Retinoid X receptor alpha, Promoter, Hepatitis B Core Antigens, Molecular biology, Artificial Gene Fusion, Genome Replication and Regulation of Viral Gene Expression, DNA-Binding Proteins, Nuclear receptor, Insect Science, DNA, Viral, Farnesoid X receptor, Dimerization, Protein Binding, Transcription Factors
Abstract

Hepatitis B virus (HBV) core promoter activity is positively and negatively regulated by nuclear receptors, a superfamily of ligand-activated transcription factors, via cis -acting sequences located in the viral genome. In this study, we investigated the role of farnesoid X receptor alpha (FXRα) in modulating transcription from the HBV core promoter. FXRα is a liver-enriched nuclear receptor activated by bile acids recognizing hormone response elements by forming heterodimers with retinoid X receptor alpha (RXRα). Electrophoretic mobility shift assays demonstrated that FXRα-RXRα heterodimers can bind two motifs on the HBV enhancer II and core promoter regions, presenting high homology to the consensus (AGGTCA) inverted repeat FXRα response elements. In transient transfection of the human hepatoma cell line Huh-7, bile acids enhanced the activity of a luciferase reporter containing the HBV enhancer II and core promoter sequences through FXRα. Moreover, using a greater-than-genome-length HBV construct, we showed that FXRα also increased synthesis of the viral pregenomic RNA and DNA replication intermediates. The data strongly suggest that FXRα is another member of the nuclear receptor superfamily implicated in the regulation of HBV core promoter activity and that bile acids could play an important role in the natural history of HBV infection.

Published
2008
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166. Hepatitis E virus mutations associated with ribavirin treatment failure result in altered viral fitness and ribavirin sensitivity

Author

Géraldine Piorkowski, Yannick Debing, Johan Neyts, Christophe Ramière, Magali Roche, Fanny Lebossé, Kai Dallmeier, Mary-Anne Trabaud, Xavier de Lamballerie, Caroline Scholtes, Patrice Andre, Catherine Legras-Lachuer, Department of Microbiology and Immunology, Rega Institute for Medical Research, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Biologie cellulaire des infections virales – Cell biology of viral infection, Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [HCL-Hôpital de la Croix Rousse], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Emergence des Pathologies Virales (EPV), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Viroscan3D SAS [Lyon, France], Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Research Foundation - Flanders (FWO), ANRS (Agence Nationale de Recherche sur le Sida et les Hepatites) [1AO2015], BELVIR consortium (IAP, phase VII) of the Belgian Science Policy Office (BELSPO), IWT SBO project HILIM-3D, École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Centre de Recherche en Cancérologie de Lyon (CRCL), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Institut Hospitalier Universitaire Méditerranée Infection (IHU AMU), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, viruses, Resistance, Drug Resistance, RNA-dependent RNA polymerase, Chronic hepatitis E, Biology, medicine.disease_cause, Virus Replication, Antiviral Agents, Virus, 03 medical and health sciences, chemistry.chemical_compound, Hepatitis E virus, Drug Resistance, Viral, Gene duplication, Ribavirin, medicine, Humans, Treatment Failure, Viral, Mutation, Hepatology, G1634R, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Hypervariable region, 030104 developmental biology, Viral replication, chemistry, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Fidelity, [SDV.IMM]Life Sciences [q-bio]/Immunology
Abstract

International audience; BACKGROUND & AIMS: Ribavirin monotherapy is the preferred treatment for chronic hepatitis E, although occasional treatment failure occurs. We present a patient with chronic hepatitis E experiencing ribavirin treatment failure with a completely resistant phenotype. We aimed to identify viral mutations associated with treatment failure and explore the underlying mechanisms. METHODS: Viral genomes were deep-sequenced at different time points and the role of identified mutations was assessed in vitro using mutant replicons, antiviral assays, cell culture of patient-derived virus and deep-sequencing. RESULTS: Ribavirin resistance was associated with Y1320H, K1383N and G1634R mutations in the viral polymerase, but also an insertion in the hypervariable region comprising a duplication and a polymerase-derived fragment. Analysis of these genome alterations in vitro revealed replication-increasing roles for Y1320H and G1634R mutations and the hypervariable region insertion. In contrast, the K1383N mutation in the polymerase F1-motif suppressed viral replication and increased the in vitro sensitivity to ribavirin, contrary to the clinical phenotype. Analysis of the replication of mutant full-length virus and in vitro culturing of patient-derived virus confirmed that sensitivity to ribavirin was retained. Finally, deep-sequencing of hepatitis E virus genomes revealed that ribavirin is mutagenic to viral replication in vitro and in vivo. CONCLUSIONS: Mutations Y1320H, G1634R and the hypervariable region insertion compensated for K1383N-associated replication defects. The specific role of the K1383N mutation remains enigmatic, but it appears to be of importance for the ribavirin resistant phenotype in this patient. LAY SUMMARY: Ribavirin is the most common treatment for chronic hepatitis E and is mostly effective, although some cases of ribavirin treatment failure have been described. Here, we report on a particular case of ribavirin resistance and investigate the underlying causes of treatment failure. Mutations in the viral polymerase, an essential enzyme for viral replication, appear to be responsible.

Published
2016
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167. Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma

Author

Soulie, Cathia, primary, Grudé, Maxime, additional, Descamps, Diane, additional, Amiel, Corinne, additional, Morand-Joubert, Laurence, additional, Raymond, Stéphanie, additional, Pallier, Coralie, additional, Bellecave, Pantxika, additional, Reigadas, Sandrine, additional, Trabaud, Mary-Anne, additional, Delaugerre, Constance, additional, Montes, Brigitte, additional, Barin, Francis, additional, Ferré, Virginie, additional, Jeulin, Hélène, additional, Alloui, Chakib, additional, Yerly, Sabine, additional, Signori-Schmuck, Anne, additional, Guigon, Aurélie, additional, Fafi-Kremer, Samira, additional, Haïm-Boukobza, Stéphanie, additional, Mirand, Audrey, additional, Maillard, Anne, additional, Vallet, Sophie, additional, Roussel, Catherine, additional, Assoumou, Lambert, additional, Calvez, Vincent, additional, Flandre, Philippe, additional, and Marcelin, Anne-Geneviève, additional

Published
2017
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168. Impact of Highly Active Antiretroviral Therapy (HAART) on the Natural History of Hepatitis B Virus (HBV) and HIV Coinfection: Relationship between Prolonged Efficacy of HAART and HBV Surface and Early Antigen Seroconversion

Author

Pierre Pradat, Bertrand Lebouché, Miché le Chevallier, Fabien Zoulim, Patrick Miailhes, Philippe Chevallier, Christian Trepo, and Mary-Anne Trabaud

Subjects
Microbiology (medical), Hepatitis B virus, HBsAg, biology, business.industry, virus diseases, Lamivudine, Hepatitis B, medicine.disease, medicine.disease_cause, biology.organism_classification, Virology, digestive system diseases, Infectious Diseases, HBeAg, Orthohepadnavirus, Immunology, Coinfection, medicine, Seroconversion, business, medicine.drug
Abstract

Background. Coinfection with hepatitis B virus (HBV) in human immunodeficiency virus (HIV)-infected patients is common. However, little is known about the natural history of chronic hepatitis B in HIV-infected populations, especially the impact of highly active antiretroviral therapy (HAART) on the outcome of HBV early antigen (HBeAg) and HBV surface antigen (HBsAg) status. Methods. The characteristics of 92 patients coinfected with HIV and HBV were retrospectively assessed before and after HAART and lamivudine treatment to determine the impact of treatment on chronic hepatitis B and factors associated with HBeAg and/or HBsAg seroconversion. Results. During follow-up, 82 patients received antiretroviral therapy, 79 of whom received HAART. Twenty-eight of the 76 patients who were administered lamivudine therapy developed lamivudine resistance mutations. While receiving antiretroviral therapy, 10 of 59 HBeAg-positive patients developed antibody to HBeAg, 3 of 10 cleared HBsAg, and 2 of 3 developed antibody to HBsAg. Two of 23 HBeAg-negative patients cleared HBsAg and developed antibody to HBsAg. HBeAg and/or HBsAg seroconversion combined with an undetectable HBV DNA level (i.e., an HBV response) correlated with a sustained HIV response (P = .001), shorter duration of antiretroviral therapy (P = .058), and more-severe disease, as evaluated by Centers for Disease Control and Prevention staging (for stage B vs. stage A, P = .029; for stage C vs. stage A, P = .069). For patients with elevated baseline alanine aminotransferase levels, the HBV response correlated significantly with a greater increase in CD4 cell count while receiving HAART. Conclusions. In HIV-HBV-coinfected patients, HBV response correlated with a sustained HIV response to antiretroviral therapy, usually HAART including lamivudine.

Published
2007
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169. Increased Regulatory T-Cell Percentage Contributes to Poor CD4(+) Lymphocytes Recovery: A 2-Year Prospective Study After Introduction of Antiretroviral Therapy

Author

Saison, Julien, Maucort Boulch, Delphine, Chidiac, Christian, Demaret, Julie, Malcus, Christophe, Cotte, Laurent, Poitevin-Later, Francoise, Miailhes, Patrick, Venet, Fabienne, Trabaud, Mary Anne, Monneret, Guillaume, Ferry, Tristan, Study, Lyon HIV Cohort, Pathogénie des Staphylocoques – Staphylococcal Pathogenesis (StaPath), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Immunologie, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie, Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Service de Biostatistiques [Lyon]

Subjects
medicine.medical_specialty, Regulatory T cell, Lymphocyte, chemical and pharmacologic phenomena, immunological failure, Gastroenterology, immune response, Major Articles, T-regulatory cells, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, Immune system, Internal medicine, medicine, 030212 general & internal medicine, IL-2 receptor, Poisson regression, Interleukin-7 receptor, Prospective cohort study, 030304 developmental biology, 0303 health sciences, business.industry, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Infectious Diseases, medicine.anatomical_structure, Oncology, Immunology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, symbols, [SDV.IMM]Life Sciences [q-bio]/Immunology, nadir CD4, business, Nadir (topography), ART
Abstract

Background. The primary aim of this study was to determine the impact of regulatory T cells (Tregs) percentage on immune recovery in human immunodeficiency virus (HIV)-infected patients after antiretroviral therapy introduction. Methods. A 2-year prospective study was conducted in HIV-1 chronically infected naive patients with CD4 count Results. Fifty-eight patients were included (median CD4 = 293/mm3, median Treg percentage = 6.1%). Percentage of Treg at baseline and CD4 nadir were independently related to the evolution of CD4 absolute value according to time: (1) at any given nadir CD4 count, 1% increase of initial Treg was associated with a 1.9% lower CD4 absolute value at month 24; (2) at any given Treg percentage at baseline, 10 cell/mm3 increase of CD4 nadir was associated with a 2.4% increase of CD4 at month 24; and (3) both effects did not attenuate with time. The effect of Treg at baseline on CD4 evolution was as low as the CD4 nadir was high. Conclusions. Regulatory T-cell percentage at baseline is a strong independent prognostic factor of immune recovery, particularly among patients with low CD4 nadir.

Published
2015
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170. Surveillance of HIV-1 primary infections in France from 2014 to 2016: toward stable resistance, but higher diversity, clustering and virulence?

Author

Visseaux, Benoit, Assoumou, Lambert, Mahjoub, Nadia, Grude, Maxime, Trabaud, Mary-Anne, Raymond, Stéphanie, Wirden, Marc, Morand-Joubert, Laurence, Roussel, Catherine, Montes, Brigitte, Bocket, Laurence, Fafi-Kremer, Samira, Amiel, Corinne, Monte, Anne De, Stefic, Karl, Pallier, Coralie, Tumiotto, Camille, Maillard, Anne, Vallet, Sophie, and Ferre, Virginie

Subjects
INFECTION, HIV, NON-nucleoside reverse transcriptase inhibitors, VIRAL load, NUCLEOSIDE reverse transcriptase inhibitors, HIV infection epidemiology, ANTI-HIV agents, HIV infections, RESEARCH, GENETICS, BIOLOGICAL evolution, SEQUENCE analysis, GENETIC mutation, RESEARCH methodology, EPIDEMIOLOGY, MEDICAL cooperation, EVALUATION research, COMPARATIVE studies, GENOTYPES, DRUG resistance in microorganisms, MICROBIAL virulence, PHARMACODYNAMICS
Abstract

Objectives: Patients with primary HIV-1 infection (PHI) are a particular population, giving important insight about ongoing evolution of transmitted drug resistance-associated mutation (TDRAM) prevalence, HIV diversity and clustering patterns. We describe these evolutions of PHI patients diagnosed in France from 2014 to 2016.Methods: A total of 1121 PHI patients were included. TDRAMs were characterized using the 2009 Stanford list and the French ANRS algorithm. Viral subtypes and recent transmission clusters (RTCs) were also determined.Results: Patients were mainly MSM (70%) living in the Paris area (42%). TDRAMs were identified among 10.8% of patients and rose to 18.6% when including etravirine and rilpivirine TDRAMs. Prevalences of PI-, NRTI-, first-generation NNRTI-, second-generation NNRTI- and integrase inhibitor-associated TDRAMs were 2.9%, 5.0%, 4.0%, 9.4% and 5.4%, respectively. In a multivariable analysis, age >40 years and non-R5 tropic viruses were associated with a >2-fold increased risk of TDRAMs. Regarding HIV diversity, subtype B and CRF02_AG (where CRF stands for circulating recombinant form) were the two main lineages (56% and 20%, respectively). CRF02_AG was associated with higher viral load than subtype B (5.83 versus 5.40 log10 copies/mL, P=0.004). We identified 138 RTCs ranging from 2 to 14 patients and including overall 41% from the global population. Patients in RTCs were younger, more frequently born in France and more frequently MSM.Conclusions: Since 2007, the proportion of TDRAMs has been stable among French PHI patients. Non-B lineages are increasing and may be associated with more virulent CRF02_AG strains. The presence of large RTCs highlights the need for real-time cluster identification to trigger specific prevention action to achieve better control of the epidemic. [ABSTRACT FROM AUTHOR]

Published
2020
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171. Stable prevalence of transmitted drug resistance mutations and increased circulation of non-B subtypes in antiretroviral-naive chronically HIV-infected patients in 2015/2016 in France.

Author

Assoumou, Lambert, Bocket, Laurence, Pallier, Coralie, Grude, Maxime, Ait-Namane, Rachid, Izopet, Jacques, Raymond, Stéphanie, Charpentier, Charlotte, Visseaux, Benoit, Wirden, Marc, Trabaud, Mary-Anne, Guillou-Guillemette, Hélène Le, Allaoui, Chakib, Henquell, Cécile, Krivine, Anne, Santos, Georges Dos, Delamare, Catherine, Bouvier-Alias, Magali, Montes, Brigitte, and Ferre, Virginie

Subjects
DRUG resistance, ANTIRETROVIRAL agents, HIV infections, INTEGRASE inhibitors, SAFE sex
Abstract

Objectives: We estimated the prevalence of transmitted-drug-resistance-associated mutations (TDRAMs) in antiretroviral-naive chronically HIV-1-infected patients.Patients and Methods: TDRAMs were sought in samples from 660 diagnosed HIV-1-infected individuals in 2015/2016 in 33 HIV clinical centres. Weighted analyses, considering the number of patients followed in each centre, were used to derive representative estimates of the percentage of individuals with TDRAMs. Results were compared with those of the 2010/2011 survey (n = 661) using the same methodology.Results: At inclusion, median CD4 cell counts and plasma HIV-1 RNA were 394 and 350/mm3 (P = 0.056) and 4.6 and 4.6 log10 copies/mL (P = 0.360) in the 2010/2011 survey and the 2015/2016 survey, respectively. The frequency of non-B subtypes increased from 42.9% in 2010/2011 to 54.8% in 2015/2016 (P < 0.001), including 23.4% and 30.6% of CRF02_AG (P = 0.004). The prevalence of virus with protease or reverse-transcriptase TDRAMs was 9.0% (95% CI = 6.8-11.2) in 2010/2011 and 10.8% (95% CI = 8.4-13.2) in 2015/2016 (P = 0.269). No significant increase was observed in integrase inhibitor TDRAMs (6.7% versus 9.2%, P = 0.146). Multivariable analysis showed that men infected with the B subtype were the group with the highest risk of being infected with a resistant virus compared with others (adjusted OR = 2.2, 95% CI = 1.3-3.9).Conclusions: In France in 2015/2016, the overall prevalence of TDRAMs was 10.8% and stable compared with 9.0% in the 2010/2011 survey. Non-B subtypes dramatically increased after 2010. Men infected with B subtype were the group with the highest risk of being infected with a resistant virus, highlighting the need to re-emphasize safe sex messages. [ABSTRACT FROM AUTHOR]

Published
2019
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172. Resistance to integrase inhibitors: a national study in HIV-1-infected treatment-naive and -experienced patients.

Author

Marcelin, Anne-Genevieve, Grude, Maxime, Charpentier, Charlotte, Bellecave, Pantxika, Guen, Laura Le, Pallier, Coralie, Raymond, Stéphanie, Mirand, Audrey, Bocket, Laurence, Fofana, Djeneba Bocar, Delaugerre, Constance, Nguyen, Thuy, Montès, Brigitte, Jeulin, Hélène, Mourez, Thomas, Fafi-Kremer, Samira, Amiel, Corinne, Roussel, Catherine, Dina, Julia, and Trabaud, Mary-Anne

Subjects
INTEGRASE inhibitors, ANTIRETROVIRAL agents, GENOTYPES, INTEGRASES
Abstract

Objectives: To describe integrase strand transfer inhibitor (INSTI) resistance profiles and factors associated with resistance in antiretroviral-naive and -experienced patients failing an INSTI-based regimen in clinical practice.Methods: Data were collected from patients failing an INSTI-containing regimen in a multicentre French study between 2014 and 2017. Failure was defined as two consecutive plasma viral loads (VL) >50 copies/mL. Reverse transcriptase, protease and integrase coding regions were sequenced at baseline and failure. INSTI resistance-associated mutations (RAMs) included in the Agence Nationale de Recherches sur le SIDA genotypic algorithm were investigated.Results: Among the 674 patients, 359 were failing on raltegravir, 154 on elvitegravir and 161 on dolutegravir therapy. Overall, 90% were experienced patients and 389 (58%) patients showed no INSTI RAMs at failure. The strongest factors associated with emergence of at least one INSTI mutation were high VL at failure (OR = 1.2 per 1 log10 copies/mL increase) and low genotypic sensitivity score (GSS) (OR = 0.08 for GSS ≥3 versus GSS = 0-0.5). Patients failing dolutegravir also had significantly fewer INSTI RAMs at failure than patients failing raltegravir (OR = 0.57, P = 0.02) or elvitegravir (OR = 0.45, P = 0.005). Among the 68 patients failing a first-line regimen, 11/41 (27%) patients on raltegravir, 7/18 (39%) on elvitegravir and 0/9 on dolutegravir had viruses with emergent INSTI RAMs at failure.Conclusions: These results confirmed the robustness of dolutegravir regarding resistance selection in integrase in the case of virological failure in routine clinical care. [ABSTRACT FROM AUTHOR]

Published
2019
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175. The risk of hospital-acquired GB virus C infection: a pilot case–control study

Author

D. Yzèbe, C. Del Signore, J. Fabry, M.A. Trabaud, Nicolas Voirin, C. Trepo, Corinne Régis, and Philippe Vanhems

Subjects
Adult, Male, Risk, Microbiology (medical), medicine.medical_specialty, Hepatitis, Viral, Human, Hepatitis C virus, GB virus C, Pilot Projects, medicine.disease_cause, Virus, Flaviviridae, Internal medicine, Bronchoscopy, medicine, Humans, Risk factor, Substance Abuse, Intravenous, Aged, Cross Infection, biology, business.industry, Case-control study, General Medicine, Odds ratio, Flaviviridae Infections, Middle Aged, biology.organism_classification, Infectious Diseases, Case-Control Studies, Cohort, Immunology, Female, business
Abstract

The risk of hospital-acquired infection with GB virus C (GBV-C) was explored among 42 patients. The factors independently associated with detection of GBV-C RNA in serum were bronchoscopic examination [adjusted odds ratio (OR)=18.1 (95% confidence interval 1.3-255.3), P=0.03] and a history of illicit drug use [OR=14.5 (1.0-218.7), P=0.05]. In this cohort of patients, invasive procedures appear to be associated with GBV-C infection but not with hepatitis C virus (HCV) infection.

Published
2003
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176. Standardized One-Step Real-Time Reverse Transcription-PCR Assay for Universal Detection and Quantification of Hepatitis Delta Virus from Clinical Samples in the Presence of a Heterologous Internal-Control RNA

Author

Christophe Ramière, Majid Amiri, Philippe Chevallier-Queyron, Fabien Zoulim, Paul Dény, Caroline Scholtes, Patrice Andre, Vinca Icard, and Mary-Anne Trabaud

Subjects
Microbiology (medical), viruses, Reproducibility of Results, RNA, Heterologous, Repeatability, Reference Standards, Viral Load, Biology, Real-Time Polymerase Chain Reaction, medicine.disease, Sensitivity and Specificity, Hepatitis D, Virology, Molecular biology, Virus, Reverse transcription polymerase chain reaction, Real-time polymerase chain reaction, medicine, Humans, Hepatitis Delta Virus, Viral load
Abstract

As for other chronic viral diseases, quantification of hepatitis delta virus (HDV) loads may be useful for patient management. We describe a one-step quantitative reverse transcription-PCR assay that is reliable and automatable and meets the regulatory authorities' standards for accurate quantification of the major HDV genotypes. It includes an internal control and uses in vitro -transcribed RNAs as standards. Its linearity range is 500 to 1.7 × 10 11 copies/ml, its sensitivity is around 150 copies/ml, its repeatability is around 15%, and its reproducibility is below 0.25 log 10 copies/ml.

Published
2012
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177. Antiretroviral-naive and -treated HIV-1 patients can harbour more resistant viruses in CSF than in plasma

Author

Soulié, Cathia, Descamps, Diane, Ronique Schneider, Vé, Trabaud, Mary-Anne, Morand-Joubert, Laurence, Delaugerre, Constance, Montes, Brigitte, Barin, Francis, Ferré, Virginie, Maillard, Anne, Vallet, Sophie, Roussel, Catherine, Assoumou, Lambert, Calvez, Vincent, Flandre, Philippe, Ve, Anne-Geneviè, Jeulin, H., Guigon, A., Lagier, E., Le Guillou, H., Alloui, C., Bettinger, D., Pallier, C., Fleury, H., Reigadas, S., Bellecave, P., Recordon-Pinson, P., Payan, C., Vabret, A., Henquell, C., Mirand, A., Bouvier-Alias, M., de Rougemont, Alexis, dos Santos, G., Morand, P., Signori-Schmuck, A., Bocket, L., Rogez, S., Andre, P., Tardy, J., Tamalet, C., Delamare, C., Schvoerer, E., André-Garnier, E., Cottalorda, J., Guinard, J., Guiguon, A., Brun-Vezinet, F., Charpentier, C., Visseaux, B., Peytavin, G., Krivine, A., Si-Mohamed, A., Avettand-Fenoel, V., Marcelin, A.-G., Lambert-Niclot, S., Wirden, M., Chaix, M., Amiel, C., Schneider, V., Giraudeau, G., Brodard, V., Plantier, J., Chaplain, C., Bourlet, T., Fafi-Kremer, S., Stoll-Keller, F., Schmitt, M., Barth, H., Yerly, S., Poggi, C., Izopet, Jacques, Raymond, S., Chaillon, A., Marque-Juillet, S., Roque-Afonso, A., Haim-Boukobza, S., Grude, Maxime, Costagliola, D., Allegre, T., Schmit, J., Chennebault, J., Bouchaud, O., Magy-Bertrand, N., Delfraissy, J., Dupon, M., Morlat, P., Neau, D., Ansart, S., Jaffuel, S., Verdon, R., Jacomet, C., Levy, Y., Dominguez, S., Chavanet, P., Piroth, L., Cabié, A., Leclercq, P., Ajana, F., Cheret, A., Weinbreck, P., Cotte, L., Poizot-Martin, I., Ravaud, I., Christian, B., Truchetet, F., Grandidier, M., Reynes, J., May, T., Goehringer, F., Raffi, F., Dellamonica, P., Prazuck, T., Hocqueloux, L., Yeni, P., Landman, R., Launay, O., Weiss, L., Viard, J., Katlama, C., Simon, A., Girard, Pascal, Meynard, J., Molina, J., Pialoux, G., Hoen, B., Goeger-Sow, M., Lamaury, I., Beaucaire, G., Jaussaud, R., Rouger, C., Michelet, C., Borsa-Lebas, F., Caron, F., Khuong, M., Lucht, F., Rey, D., Calmy, A., Marchou, B., Gras, G., Greder-Belan, A., Vittecoq, D., Teicher, E., Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de bactériologie-virologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Génétique et Ecologie des Virus, Génétique des Virus et Pathogénèse des Maladies Virales, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre national de référence du VIH INSERM U966, Université de Tours (UT), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Pontchaillou [Rennes], Laboratoire de Parasitologie et Mycologiede [CHRU Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Modélisation mathématique, calcul scientifique (MMCS), Institut Camille Jordan [Villeurbanne] (ICJ), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet [Saint-Étienne] (UJM)-Centre National de la Recherche Scientifique (CNRS), Service de Virologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Neuroimagerie cognitive (LCogn), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire de Virologie Humaine et Moléculaire [Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Faculté de médecine et pharmacie, CHU Clermont-Ferrand, Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), UFR des Sciences de Santé (Université de Bourgogne), Université de Bourgogne (UB), Centre National de Référence des virus entériques [CHU de Dijon] (CNR virus entériques), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de sérologie-virologie (CHU de Dijon), Procédés Alimentaires et Microbiologiques [Dijon] (PAM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Biologie structurale des interactions entre virus et cellule hôte (UVHCI), Université Joseph Fourier - Grenoble 1 (UJF)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Laboratoire d'Informatique de Nantes Atlantique (LINA), Mines Nantes (Mines Nantes)-Université de Nantes (UN)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'électronique, optoélectronique et microsystèmes (LEOM), Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Hôtel-Dieu de Nantes, Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Equipe de Recherche en Physico-Chimie et Biotechnologie (ERPCB), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Interactions et dynamique des environnements de surface (IDES), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [Strasbourg], Interaction virus-hôte et maladies du foie, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Environment and Sustainable Development Programme, European Commission - DG Research and Innovation, Centre Hospitalier Intercommunal de Toulon - La Seyne-sur-Mer, Laboratoire de Virologie [Toulouse], CHU Toulouse [Toulouse], Magnétisme et Diffusion Neutronique (MDN), Modélisation et Exploration des Matériaux (MEM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier du Pays d'Aix, CHU Bordeaux [Bordeaux], Fédération des Maladies Infectieuses [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Service de médecine interne 2 et maladies infectieuses, Unité de Maladies Infectieuses et Tropicales [CHU Caen], Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Dijon, Département d'infectiologie (CHU de Dijon), Centre d'Investigation Clinique Antilles-Guyane (CIC - Antilles Guyane), Université des Antilles et de la Guyane (UAG)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Bell Labs (BELL), Lucent Technologies, Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Service des maladies infectieuses et tropicales [CHU Nantes], CIC - Biotherapie - AP-HP (cochin - Pasteur), Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut d’Electronique et des Systèmes (IES), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Médecine interne, Maladies Infectieuses et Immunologie Clinique [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Institut supérieur de l'électronique et du numérique (ISEN)-Université de Valenciennes et du Hainaut-Cambrésis (UVHC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF), CHU Saint-Etienne, CHU Strasbourg, Geneva University Hospital (HUG), Service de Maladies Infectieuses et Tropicales [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, CHU Besançon, Université de Franche-Comté (UFC), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Laboratoire Universitaire de Biodiversité et Ecologie Microbienne (LUBEM), Université de Brest (UBO), Laboratoire Microorganismes : Génome et Environnement - Clermont Auvergne (LMGE), Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie structurale des interactions entre virus et cellule hôte, Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), CHU Orléans, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Pitié-Salpêtrière [APHP], Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7), University of Applied Sciences Kaiserslautern, Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Hopital l'Archet, Centre d'Information et de Soins de I'Immunodéficience Humaine (CISIH). Hôpital l'Archet 1, Hôpital l'Archet, REseau national d'Investigation clinique en VACcinologie (REIVAC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Hôtel-Dieu-Groupe hospitalier Broca-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de Gestion des Essais de Produits de Santé (CeNGEPS), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Estación Experimental de Pastos y Forrajes 'Indio Hatuey', Société Ragt 2N, Service des maladies infectieuses et tropicales [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), University Hospital and University Jean Monnet, Laboratoire d'Ecologie Alpine (LECA), Centre National de la Recherche Scientifique (CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Université Joseph Fourier - Grenoble 1 (UJF)-Université Grenoble Alpes (UGA), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Camille Jordan (ICJ), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Université de Tours, Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, European Molecular Biology Laboratory [Grenoble] (EMBL)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), CHU de Fort de France-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-CHU Pointe-à-Pitre/Abymes [Guadeloupe] -Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles et de la Guyane (UAG), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Centre National de la Recherche Scientifique (CNRS)-Mines Nantes (Mines Nantes)-Université de Nantes (UN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Laboratoire de virologie, Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Jean Monnet [Saint-Étienne] (UJM)-École Centrale de Lyon (ECL), Université de Lyon, Université Grenoble Alpes (UGA), Station de recherches sur la vache laitière, Institut National de la Recherche Agronomique (INRA), Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Hôpital Arnaud de Villeneuve, T2, Laboratoire Matériaux Optiques, Photonique et Systèmes (LMOPS), CentraleSupélec-Université de Lorraine (UL)-CentraleSupélec-Université de Lorraine (UL), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Institut d’Électronique, de Microélectronique et de Nanotechnologie (IEMN) - UMR 8520 (IEMN), Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Université Polytechnique Hauts-de-France (UPHF)-Ecole Centrale de Lille-Université Polytechnique Hauts-de-France (UPHF)-Institut supérieur de l'électronique et du numérique (ISEN), and de ROUGEMONT, Alexis

Subjects
Male, Drug Resistance, HIV Infections, medicine.disease_cause, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Antiretroviral Therapy, Highly Active, Genotype, Pharmacology (medical), 030212 general & internal medicine, Viral, ComputingMilieux_MISCELLANEOUS, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, ddc:616, 0303 health sciences, Mutation, medicine.diagnostic_test, Proteolytic enzymes, virus diseases, Pharmacology and Pharmaceutical Sciences, Viral Load, Middle Aged, 3. Good health, ANRS Resistance AC11 Group, Infectious Diseases, Medical Microbiology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV/AIDS, ARV, Female, Infection, Viral load, Microbiology (medical), Adult, Anti-HIV Agents, Antiretroviral Therapy, CSF, Microbial Sensitivity Tests, Biology, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, Microbiology, Virus, resistance, 03 medical and health sciences, Clinical Research, Drug Resistance, Viral, medicine, Genetics, Humans, Highly Active, Gene, Pharmacology, 030306 microbiology, Lumbar puncture, Neurosciences, HIV, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Reverse transcriptase, Immunology, HIV-1, Antimicrobial Resistance, Nervous System Diseases
Abstract

International audience; Objectives: The neurological disorders in HIV-1-infected patients remain prevalent. The HIV-1 resistance in plasma and CSF was compared in patients with neurological disorders in a multicentre study. Methods: Blood and CSF samples were collected at time of neurological disorders for 244 patients. The viral loads were .50 copies/mL in both compartments and bulk genotypic tests were realized. Results: On 244 patients, 89 and 155 were antiretroviral (ARV) naive and ARV treated, respectively. In ARV-naive patients, detection of mutations in CSF and not in plasma were reported for the reverse transcriptase (RT) gene in 2/89 patients (2.2%) and for the protease gene in 1/89 patients (1.1%). In ARV-treated patients, 19/152 (12.5%) patients had HIV-1 mutations only in the CSF for the RT gene and 30/151 (19.8%) for the protease gene. Two mutations appeared statistically more prevalent in the CSF than in plasma: M41L (P ¼ 0.0455) and T215Y (P ¼0.0455). Conclusions: In most cases, resistance mutations were present and similar in both studied compartments. However, in 3.4% of ARV-naive and 8.8% of ARV-treated patients, the virus was more resistant in CSF than in plasma. These results support the need for genotypic resistance testing when lumbar puncture is performed.

Published
2015
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178. Persistent production of an integrase-deleted HIV-1 variant with no resistance mutation and wild-type proviral DNA in a treated patient

Author

Christophe Ramière, Patrice Andre, Fabienne Venet, Mary-Anne Trabaud, Laurent Cotte, Corinne Ronfort, Guillaume Monneret, Jean-Claude Tardy, J. Saison, Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Rétrovirus et Pathologie Comparée (RPC), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL), Hospices Civils de Lyon [D50624], École pratique des hautes études (EPHE), and Université de Lyon-Université de Lyon-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)

Subjects
Viral/genetics, [SDV]Life Sciences [q-bio], Mutant, HIV Infections, Defective virus, Lopinavir, Proviruses, Leukocytes, Polymerase, Sequence Deletion, 0303 health sciences, biology, Defective Viruses, Viral Load, Resistance mutation, Mononuclear/virology, 3. Good health, Integrase, Infectious Diseases, Lamivudine, Combination, Drug Therapy, Combination, Zidovudine, Sequence Analysis, Anti-HIV Agents, HIV Infections/*drug therapy/genetics, Zidovudine/therapeutic use, Immunology, Molecular Sequence Data, Defective Viruses/genetics/*pathogenicity, Integrases/*genetics, HIV-1/*genetics, Virus, 03 medical and health sciences, Drug Therapy, Virology, Humans, Lamivudine/therapeutic use, Gene, Proviruses/genetics, 030304 developmental biology, Immune Evasion, Lopinavir/therapeutic use, Immune Evasion/genetics, Integrases, Base Sequence, 030306 microbiology, Wild type, Sequence Analysis, DNA, DNA, Molecular biology, Viral Load/drug effects, DNA, Viral, biology.protein, HIV-1, Leukocytes, Mononuclear, Anti-HIV Agents/*therapeutic use
Abstract

Supplementary Data; International audience; An HIV-infected patient presenting an unexpected viral escape under combined antiretroviral treatment is described. The virus isolated from plasma contained a large deletion in the HIV-1 integrase gene but no known resistance mutation. Nested polymerase chain reactions (PCRs) with patient virus integrase-specific primers and probes were developed and used to detect the mutant from plasma, blood, rectal biopsies, and sperm. The variant progressively emerged during a period of therapy-induced virosuppression, and persisted at a low but detectable level for at least 5 years. Surprisingly, proviral DNA from lymphocytes, rectal cells, and sperm cells was, and remained, mainly wild type. Cellular HIV RNA with the deletion was detected only once from the rectum. The origin and mechanisms underlying this so far not described production at a detectable level are largely hypothetical. This observation raised concern about the ability of defective viruses to spread.

Published
2015
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179. Recent evidence of underestimated circulation of hepatitis C virus intergenotypic recombinant strain RF2k/1b in the Rhône-Alpes region, France, January to August 2014: implications for antiviral treatment

Author

Patrice Morand, Mary-Anne Trabaud, Jean Nana, P Tremeaux, Pascal André, M.A. Thelu, Fanny Lebossé, François Bailly, C. Ramière, Vincent Leroy, Sylvie Larrat, A Caporossi, Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), and Thomas, Frank

Subjects
MESH: Antiviral Agents, Genotype, Epidemiology, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Hepatitis C virus, Genome, Viral, Hepacivirus, Biology, Viral Nonstructural Proteins, MESH: Base Sequence, medicine.disease_cause, Antiviral Agents, law.invention, MESH: Genotype, law, Virology, medicine, Humans, MESH: Hepacivirus, Antiviral treatment, MESH: Phylogeny, Genotyping, Phylogeny, MESH: Treatment Outcome, Recombination, Genetic, MESH: Hepatitis C, MESH: Humans, Base Sequence, Strain (biology), Public Health, Environmental and Occupational Health, Hepatitis C, MESH: France, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Treatment Outcome, MESH: RNA, Viral, Recombinant DNA, RNA, Viral, MESH: Viral Nonstructural Proteins, MESH: Recombination, Genetic, France, MESH: Genome, Viral
Abstract

International audience; Since the beginning of 2014, hepatitis C virus (HCV) recombinant forms RF2k/1b have been detected in the Rhône-Alpes French region in 10 patients originating from the Caucasus area. Circulation of this particular HCV strain is very likely to be underestimated. It is also prone to be misgenotyped when using genotyping methods based on the 5' region of the viral genome, which may lead to suboptimal treatment.

Published
2014

180. Virological failure of patients on maraviroc-based antiretroviral therapy

Author

Stéphanie, Raymond, Anne, Maillard, Corinne, Amiel, Gilles, Peytavin, Mary Anne, Trabaud, Delphine, Desbois, Pantxika, Bellecave, Constance, Delaugerre, Cathia, Soulie, Anne Geneviève, Marcelin, Diane, Descamps, Jacques, Izopet, J, Izopet, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT), Laboratoire Virologie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacocinétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de microbiologie [Saint-Louis], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées, Laboratoire de Virologie, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Tenon [APHP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
Microbiology (medical), Adult, Male, resistance to maraviroc, viruses, [SDV]Life Sciences [q-bio], Population, Drug Resistance, Antiretroviral Therapy, HIV Infections, Drug resistance, Biology, Maraviroc, chemistry.chemical_compound, Cyclohexanes, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, HIV tropism, Humans, Pharmacology (medical), Highly Active, Viral, Treatment Failure, education, Genotyping, Tropism, Aged, Retrospective Studies, Pharmacology, CXCR4, education.field_of_study, HIV-1 tropism determination, phenotypic assay, Middle Aged, Triazoles, Viral Load, Virology, 3. Good health, Viral Tropism, Infectious Diseases, chemistry, Anti-Retroviral Agents, Immunology, Tissue tropism, HIV-1, entry, Female, Viral load
Abstract

Objectives Virological failure (VF) in patients on maraviroc-based treatment has been associated with altered HIV tropism and resistance to maraviroc. This multicentre study aimed to characterize VF in patients treated with maraviroc. Methods We analysed 27 patients whose treatment failed between 2008 and 2011. They had been screened for HIV tropism before maraviroc initiation using population-based V3 genotyping. HIV-1 tropism and resistance of R5 viruses to maraviroc at VF and at baseline were determined retrospectively using an ultrasensitive recombinant virus assay (RVA). Results Viruses from 27 patients given maraviroc on the basis of the R5 genotype were characterized at the time of treatment failure. The RVA indicated that 12 patients harboured CXCR4-using viruses and 15 (56%) had pure R5 viruses at failure. One-third of those harbouring CXCR4-using viruses (4/12) were infected with R5X4/X4 viruses according to the RVA before maraviroc initiation. We analysed the phenotypic resistance to maraviroc of four patients harbouring R5 viruses at failure; two harboured viruses whose maximum percentage inhibition was reduced by 65%–90%, while the other two were infected with susceptible viruses. All patients had effective concentrations of drugs. Conclusions Half of the maraviroc-treated patients who experienced VF harboured CXCR4-using viruses at failure, one-third of them were detected by a phenotypic method before maraviroc initiation. Phenotypic assessment of R5 virus resistance to CCR5 antagonists at failure could help optimize antiretroviral therapy.

Published
2014
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181. Persistent production of an integrase-deleted HIV-1 variant with no resistance mutation and wild-type proviral DNA in a treated patient

Author

C Ronfort, Christophe Ramière, Mary-Anne Trabaud, P. André, J. C. Tardy, Laurent Cotte, and J. Saison

Subjects
medicine.medical_specialty, Pathology, Protease, medicine.medical_treatment, Wild type, virus diseases, Viremia, Biology, medicine.disease, Resistance mutation, Virology, Reverse transcriptase, Integrase, Infectious Diseases, Medical microbiology, medicine, biology.protein, Oral Presentation, Gene
Abstract

An HIV-1-infected patient with suppressed viremia for several years, in whom a variant carrying a deleted integrase (IN) gene, without reverse transcriptase (RT) or protease (PR) resistance mutations, emerged in the plasma and persisted is described.

Published
2014
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182. DO LIGHT AND LITTER INFLUENCE THE RECRUITMENT OF CISTUS SPP. STANDS?

Author

Louis Trabaud and Philippe Renard

Subjects
education.field_of_study, Population, Plant Science, Soil surface, Biology, Plant litter, biology.organism_classification, Vegetation cover, Agronomy, Disturbance (ecology), Germination, Botany, Cistus, Litter, education, Agronomy and Crop Science, Ecology, Evolution, Behavior and Systematics
Abstract

After a major disturbance (such as fire or soil upsetting), large numbers ofCistusspp. seedlings may appear and ensure population recruitment, but in the absence of such disturbances seedlings are rare or nonexistent in matureCistusstands. What are the causes? Two factors, little studied until now, have been examined: the influence of litter and of light reaching the soil surface. In two types of stands, one dominated by C.monspeliensisand the other byC. albidus, an experiment was undertaken by removing the vegetation cover and by the presence or absence of litter to examine the establishment of seedlings. The seed bank in the soil was also studied to determine its size. Seeds were also subjected to a temperature of 52 °C to simulate exposure to full sunlight in summer and determine whether this had any affect on their germination rate.Light and litter had no effect on the germination, irrespective of the quality or intensity of light reaching the soil or the presence or absence of litter; there were always few seedlings and there was no significant difference in numbers between treatments. There was a large seed bank in the soil and these seeds were capable of germinating following experimental conditions: the heat stress applied proved to be too slight to break seed dormancy, although they were viable because they germinated after scarification. In existingCistusspp. stands,Cistusspp. seeds germinate with difficulty, and lack of recruitment could lead to disappearance of local communities unless they are subjected to disturbances.

Published
1999
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183. Maraviroc/raltegravir simplification strategy following 6 months of quadruple therapy with tenofovir/emtricitabine/maraviroc/raltegravir in treatment-naive HIV patients

Author

Pradat, Pierre, primary, Durant, Jacques, additional, Brochier, Corinne, additional, Trabaud, Mary-Anne, additional, Cottalorda-Dufayard, Jacqueline, additional, Izopet, Jacques, additional, Raffi, François, additional, Lucht, Frédéric, additional, Gagnieu, Marie-Claude, additional, Gatey, Caroline, additional, Jacomet, Christine, additional, Vassallo, Matteo, additional, Dellamonica, Pierre, additional, and Cotte, Laurent, additional

Published
2016
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185. In Vivo Tropism of Hepatitis C Virus Genomic Sequences in Hematopoietic Cells: Influence of Viral Load, Viral Genotype, and Cell Phenotype

Author

Christian Trepo, Françoise Berby, Sylvie Rumin, François Habersetzer, Mary-Anne Trabaud, Geneviève Inchauspe, and Hervé Lerat

Subjects
Adult, Male, Genotype, Neutrophils, Hepacivirus, Hepatitis C virus, T-Lymphocytes, Immunology, medicine.disease_cause, Virus Replication, Polymerase Chain Reaction, Sensitivity and Specificity, Biochemistry, Virus, Monocytes, Cohort Studies, Phagocytosis, medicine, Humans, Viremia, Aged, Hepatitis, Chronic, B-Lymphocytes, biology, Macrophages, RNA, Cell Biology, Hematology, Middle Aged, biology.organism_classification, Virology, Hepatitis C, Phenotype, Viral replication, Carrier State, RNA, Viral, Female, Viral disease, Viral load
Abstract

Extrahepatic sites capable of supporting hepatitis C virus (HCV) replication have been suggested. We analyzed the influence of virological factors such as viral genotype and viral load, and cellular factors such as cell phenotype, on the detection rate of HCV sequences in hematopoietic cells of infected patients. Thirty-eight chronically infected patients were included in the study: 19 infected by genotype 1 isolates (1a and 1b), 13 by nongenotype 1 isolates (including genotypes 2 a/c, 3a, and 4), and 6 coinfected by genotype 1 and 6 isolates. Polymerase chain reaction (PCR) detection efficiency of viral genomic sequences, both the positive and negative strand RNA, was evaluated using RNA transcripts derived from genotype 1, 2, 3, and 4 cloned sequences and found to be equivalent within one log unit. The serum viral load, ranging from less than 2 × 105 Eq/mL to 161 × 105 Eq/mL, did not influence the detection rate of either strand of RNA in patients' peripheral blood mononuclear cells (PBMCs). Positive and negative strand RNA were found in PBMCs of all 3 cohorts of patients with a detection rate ranging from 15% to 100% and from 8% to 83.3% for the positive and negative strand RNA, respectively. Coinfected patients showed a detection rate in all cases greater than 80%. Patients infected with genotype 1 isolates showed a higher detection rate of either strands of RNA when compared with patients infected with other genotypes (P < .001 andP < .04). Both strands were found restricted to polymorphonuclear leukocytes, monocytes/macrophages, and B (but not T) lymphocytes. These data show that HCV genomic sequences, possibly reflecting viral replication, can be detected in PBMCs of chronically infected patients independent of the viral load and that specific associated cell subsets are implicated in the harboring of such sequences.

Published
1998
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186. Synthesis of New Tetrakis N-Substituted Tetra-Azamacrocycles

Author

Michel Camplo, Jean Dessolin, C. Trabaud, and L. J. Kraus

Subjects
chemistry.chemical_classification, chemistry, biology, Organic Chemistry, Tetra, Reaction type, biology.organism_classification, Medicinal chemistry, Alkyl
Abstract

The synthesis of new tetra-kis N- substituted tetra-azamacrocyles was achieved. In the case of tetra amido analogues the best yields were obtained through the use of Schotten - Bauman reaction type in a biphasic system. In the case of tetra-N- ω alkyl carboxylic esters, optimal experimental conditions leading to the desired tetra N-substituted derivatives are described.

Published
1998
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187. Historique de la création de la Réserve Naturelle de Roque-Haute et sa végétation

Author

Louis Trabaud

Subjects
Geographic distribution, historique, dynamique, Roque-Haute, mares temporaires, Isoetes, Geography, Ecology, historical account, temporary pounds, dynamics, Forestry, Vegetation dynamics, Mediterranean vegetation, Ecology, Evolution, Behavior and Systematics
Abstract

During the sixties and the development of the littoral Languedoc-Roussillon, the establishment of areas of protected biological interest (to be included in the development plan) were asked of the Mission Interministérielle pour l’Aménagement du Littoral Languedoc-Roussillon. Thus, fifteen sites to be protected were selected including the plateau of Roque-Haute and its ponds. A first working phase allowed identification of the areas and their scientific interest. The second phase was the mapping of plant communities at the cadastral level in order to establish what were the species to be protected. The final report delivered to the Mission for establishing the conservation documents, included the cartography, the cadastral survey and the owners names, and also the scientific arguments for allowing the preservation orders. Between the visits and surveys in the years 1964/65 (to obtain the scientific criteria for establishment of the conservation documents), a vegetation mapping, and a visit at the beginning of summer 1 997, many changes have occurred in the terrestrial vegetation. At that time, the plateau was mainly covered by a low garrigue dominated by Cistus monspeliensis and Brachypodium retusum, kept in check by fire and grazing ; human action was quite strong. The ponds were used by livestock for drinking and grazing. Now, the vegetation of the plateau constitutes a low garrigue in which Quercus ilex and Phillyrea angustifolia are dominant. Cistus is disappearing. Woody vegetation seems to be denser. The ponds which are not permanently full are encroached by trees of Ulmus campestris, Fraxinus angustifolia subsp. oxycarpa, Tamarix gallica (these two last tree species were not observed in 1964/65). The ponds with water in summer (deeper) are invaded by Typha angustifolia., Au cours des années soixante, lors de l’aménagement du littoral du Languedoc-Roussillon, la protection et la mise en réserve de zones d’intérêt biologique à conserver furent demandées dans le cadre des actions de la Mission Interministérielle pour l’Aménagement du Littoral Languedoc-Roussillon. Ainsi une quinzaine de sites à protéger furent proposés, dont le plateau de Roque-Haute et ses mares. Une première étape permit d’identifier les zones et de préciser leur intérêt scientifique. Une deuxième étape fut la cartographie de la végétation au niveau parcellaire (cadastre), afin de délimiter réellement les unités à protéger. Dans le rapport final, remis à la Mission pour dresser le dossier de classement, figuraient cette cartographie, l’état parcellaire des zones et des propriétaires, ainsi que les arguments scientifiques permettant le classement. Entre les visites des années 1964-1965 (pour établir les critères scientifiques de classement du site), une cartographie réalisée en 1992, et la visite effectuée en juin 1997, d’importants changements sont apparus dans la végétation terrestre. A l’époque, le plateau était principalement recouvert par une garrigue basse à Cistus monspeliensis et Brachypodium retusum, maintenue en l’état par le feu et le pâturage ; l’action de l’homme y était encore assez forte. Les mares étaient utilisées par le bétail pour boire ou pâturer. Actuellement, la végétation du plateau est constituée par une garrigue basse, dominée par Quercus ilex et Phillyrea angustifolia. Les cistes sont en voie de disparition. La végétation arbustive semble s’être densifiée. Les mares qui ne sont pas en permanence en eau sont envahies par des individus de Ulmus campestris, Fraxinus angustifolia subsp. oxycarpa, Tamarix gallica (ces deux dernières espèces d’arbres n’avaient pas étaient notées en 1964-1965). Les mares qui conservent leur eau jusqu’en été (mares profondes) sont envahies par Typha angustifolia., Trabaud Louis. Historique de la création de la Réserve Naturelle de Roque-Haute et sa végétation. In: Ecologia mediterranea, tome 24 n°2, 1998. pp. 173-177.

Published
1998
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188. Végétation épigée et banque de semences du sol: leur contribution à la stabilité cyclique des pinèdes mixtes de Pinus halepensis et P. pinaster

Author

Pablo Ferrandis, Juan J. Martínez-Sánchez, Louis Trabaud, José M. Herranz, and Ana I. González-Ochoa

Subjects
Soil test, Perennial plant, Soil seed bank, Pine forest, Botany, food and beverages, Mediterranean area, Plant Science, Vegetation, Trifolium glomeratum, Biology, biology.organism_classification, Floristics
Abstract

After fire (a frequent phenomenon in the Mediterranean area), numerous seedlings appear from seeds of the soil seed bank that would not appear would there be no fire. Why this sudden advent? To which species do they belong? Vegetation records were made in a 12-year-old mixed pine forest of Pinus halepensis and P. pinaster. At the same time, soil samples were collected (5 cm deep). The direct method (identification with binocular lens of all encountered seeds after soil screening) was used to identify seeds to species. Seeds of species encountered in large quantity were subjected to viability tests. The seeds of two therophytes (Trifolium glomeratum, T. campestre) were subjected to thermal treatments. The soil seed bank was only partially reflecting the floristic composition of the pine forest. Three groups of plants were distinguished: (i) species observed both in aboveground vegetation and in the soil seed bank (21.9%); all were perennials, (ii) species encountered only in the vegetation (58.5%); those preferentially regenerated by vegetative means, and (iii) species observed only in the soil seed bank (19.5%); most reproduced only from seeds. The number of seeds in the soil was high and their distribution very variable. The higher the number of plots in which seeds of a species appeared, the more numerous were the total seeds of that species recorded. Thus, Cistus ladanifer was present in great quantity in all samples. In seeds of species subjected to thermal treatments, low temperatures (50–90 °C) did not increase germination rates, but exposure to high temperatures (130–150 °C) for long duration (10 min) killed the embryo. In conclusion, numerous seeds are present in a dormant stage in the soil. When a disturbance such as fire eliminates temporarily the aboveground vegetation, these seeds germinate. Thus, after a fire, the seedlings of these species proliferate, then these species disappear with representation by seeds in latent form in the soil when perennial aboveground vegetation has reoccupied burned areas. Key words: seeds, soil seed bank, fire, thermal treatments.

Published
1997
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189. INFLUENCE OF FIRE ON PLANT REGENERATION IN A STIPA TENACISSIMA L. COMMUNITY IN THE SIERRA LARGA MOUNTAIN RANGE (SE SPAIN)

Author

Juan J. Martínez-Sánchez, José María Herranz, Louis Trabaud, and Juan Guerra

Subjects
Juniperus phoenicea, biology, Ecology, ved/biology, Range (biology), ved/biology.organism_classification_rank.species, Plant Science, biology.organism_classification, Floristics, Geography, Plant cover, Species richness, Endemism, Agronomy and Crop Science, Ecology, Evolution, Behavior and Systematics, Cistus clusii, Stipa tenacissima
Abstract

The range of communities dominated byStipa tenacissimaextends from Ukraine to North Africa. They contain several endemic species in Spain. The post-fire response of a community ofS. tenacissimain semiarid SE Spain was studied by following the dynamics of the floristic richness and plant cover during the first four years. The importance ofS. tenacissimawas noticed during recolonization of these zones, where, three years after a fire, the high degree of cover was similar to that of unburned areas.The prolonged drought during the study period was the probable cause of difficulties in recolonization of the burned area by the three obligate seeder species (Pinus halepensis, Rosmarinus officinalis, andCistus clusii) which were widespread in the unburned community.Juniperus phoeniceadid not sprout after the fire, and four years later no seedlings were encountered in the burned area. According to the results, the endemic plants living in theS. tenacissimacommunity were not negatively affected by fire; the twelve endemic species found in this community were all capable of responding to the fire either through new shoots or by reproduction through seeds.

Published
1997
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190. Modelisation, Synthesis and Anti-HIV activities of N,N,N′,N″,N‴-pentakistetraazamacrocycles salts derivatives

Author

M. Bouygues, Michel Camplo, Patrick Vlieghe, C. Trabaud, Jean-Louis Kraus, Jean Dessolin, and Jean-Claude Chermann

Subjects
Molecular model, Chemistry, Stereochemistry, Anti hiv, Organic Chemistry, Clinical Biochemistry, Human immunodeficiency virus (HIV), Pharmaceutical Science, chemistry.chemical_element, Zinc, medicine.disease_cause, Biochemistry, Chemical synthesis, Drug Discovery, medicine, Molecular Medicine, Chelation, Molecular Biology
Abstract

The syntheses and the anti-HIV activities of new N,N,N′,N″,N‴-pentakistetraazamacrocyles salts analogues are described. From computer modeling studies, it was found that zinc coordination capacity of these pentakis derivatives was larger than the one of the corresponding tetrakis analogues. This suggest that a metal chelation energy could be a criteria to design novel anti-HIV polyazamacrocyles. © 1997 Elsevier Science Ltd.

Published
1997
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191. Urea cyclisation reaction studies

Author

V. Niddam, M. Medou, Michel Camplo, Jean-Louis Kraus, Jean Dessolin, and C. Trabaud

Subjects
chemistry.chemical_compound, chemistry, Organic Chemistry, Condensation, Urea, Organic chemistry, Urea derivatives, Glyoxylic acid, Catalysis
Abstract

Synthetic approaches of N-α-hydroxyalkyl amides or urea derivatives are described. In particularly, a new 1,4,6-oxadiazocine-2,5,8-trione was obtained by condensation of glyoxylic acid on urea derivatives in acidic catalysis condition.

Published
1997
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193. HIV-1 integrase variability and relationship with drug resistance in antiretroviral-naive and -experienced patients with different HIV-1 subtypes

Author

S, Reigadas, A G, Marcelin, A, Houssaïni, S, Yerly, D, Descamps, J C, Plantier, A, Ruffault, C, Amiel, M A, Trabaud, Philippe, Flandre, H, Fleury, B, Masquelier, S, Marque-Juillet, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Epidémiologie, stratégies thérapeutiques et virologie cliniques dans l'infection à VIH, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de virologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Unité de Rétrovirologie, Hôpital Pontchaillou, Infectious Diseases Department, Université Montpellier 1 (UM1), Virology Laboratory, Bordeaux University Hospital, Bordeaux, France, Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Service de virologie [CHU Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Département de microbiologie : Bactério, Virologie, Parasito, Hygiène-Hôpital Charles Nicolle [Rouen]-CHU Rouen

Subjects
Microbiology (medical), Anti-HIV Agents, HIV Integrase/genetics, Molecular Sequence Data, Human immunodeficiency virus (HIV), Mutation, Missense, HIV Infections, Drug resistance, HIV Integrase, Bioinformatics, medicine.disease_cause, 03 medical and health sciences, Anti-HIV Agents/pharmacology, Drug Resistance, Viral, medicine, Antiretroviral naive, Humans, Pharmacology (medical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, ddc:616, HIV-1/drug effects/genetics/isolation & purification, Pharmacology, 0303 health sciences, biology, Group study, 030306 microbiology, Genetic Variation, Sequence Analysis, DNA, Hiv subtype, Virology, 3. Good health, Integrase, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Hiv 1 integrase, biology.protein, HIV-1, HIV Infections/virology
Abstract

H-932. American Society for Microbiology, Washington, DC, USA. 10 Nouhin J, Donchai T, Hoang KT et al. Natural polymorphisms of HIV-1 CRF01_AE integrase coding region in ARV-naive individuals in Cambodia, Thailand and Vietnam: an ANRS AC12 working group study. Infect Genet Evol 2011; 11: 38–43. 11 Wainberg MA, Brenner BG. Role of HIV subtype diversity in the development of resistance to antiviral drugs. Viruses 2010; 2: 2493–508. Research letter

Published
2013

194. Modelisation, synthesis and antiviral evaluation of new 2,3-disubstituted thiazolidinone nucleoside analogues

Author

Jean-Louis Kraus, Jean Dessolin, Fabien Zoulim, JC Graciet, Christelle Borel, Nicolas Mourier, Jean-Claude Chermann, C. Trabaud, Michel Camplo, M. Medou, M. Gamberoni, Olivier Hantz, and V. Niddam

Subjects
Molecular model, Chemistry, Stereochemistry, Organic Chemistry, Clinical Biochemistry, Drug Discovery, Synthon, Pharmaceutical Science, Molecular Medicine, Molecular Biology, Biochemistry, Nucleoside, Combinatorial chemistry
Abstract

The syntheses, anti-HIV and anti-HBV in vitro evaluations of new thiazolidinone nucleoside analogues are described. Preliminary molecular modeling studies demonstrated that these new analogues conserved the essential elements of the hypothesized biological active synthon.

Published
1996
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195. Synthesis and Anti-HIV Evaluation of New 5-Substituted-2′,3′-Dideoxy-3′-thiauridine Nucleosides

Author

V. Niddam, Jean-Louis Kraus, Nicolas Mourier, C. Trabaud, Jean-Claude Chermann, Michel Camplo, and J. C. Graciet

Subjects
chemistry.chemical_compound, Trimethylsilyl, chemistry, Molecular model, medicine.drug_class, Anti hiv, Genetics, medicine, Carboxamide, Biochemistry, Trifluoromethanesulfonate, Combinatorial chemistry, Reverse transcriptase
Abstract

On the basis of molecular modeling calculations using Gen Mol software, new 5-substituted-2′,3′-dideoxy-3′-thiauridine were designed as possible anti-HIV reverse transcriptase inhibitors. The synthesis of the key intermediate 5-carboxy-2′,3′-dideoxy-3′-thiauridine was achieved through the condensation of the fully silylated 5-carboxyuracil on 2-benzoyl methyl-5-acetoxy-1,3-oxathiolane using trimethylsilyl triflate (TMSOTf). This latter compound was condensed with 2-(N-tert-Butoxycarbonyl)-1 -aminoethane in the presence of N, N-diisopropylethylamine (DIEA). The subsequent carboxamide deprotection led to the final compounds. These new analogues were evaluated for their anti-HIV-1 activities on infected MT4 cells but no significant protection was observed. Electronic and structural parameters considered in this model were not sufficient to predict any active anti-HIV molecular structures.

Published
1996
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196. Synthesis and antiviral activity of N-4′-dihydropyridinyl and dihydroquinolinylcarbonyl-2-hydroxymethyl-5-[cytosin-1′-yl]-1,3-oxathiolane derivatives against human immunodeficiency virus and duck hepatitis B virus

Author

C. Trabaud, Olivier Hantz, Jean-Claude Chermann, V. Niddam, Nicolas Mourier, Fabrice Turin, Jean-Louis Kraus, Michel Camplo, Christelle Borel, JC Graciet, and A. S. Charvet‐Faury

Subjects
Pharmacology, biology, Chemistry, Stereochemistry, Organic Chemistry, Niflumic acid, Dihydropyridine, Duck hepatitis B virus, General Medicine, Prodrug, biology.organism_classification, Duck hepatitis virus, Chemical synthesis, chemistry.chemical_compound, Drug Discovery, Lipophilicity, medicine, Hydroxymethyl, medicine.drug
Abstract

Summary Dihydropyridine and dihydroquinoline derivatives of 2-hydroxymethyl-5-[cytosin-1′-yl]- 1,3-oxathiolane ((±)-3TC) have been prepared. The N--4-nicotinate or the N--4-quinoline-carboxylate amides were obtained by reacting nicotinic or quinolinecarboxylic acids with (±)-3TC in the presence of DCC and HOBT. These derivatives were converted into their corresponding N--methylpyridinium and N--methyl quinolinium salts by treatment with MeI in acetone. Reduction of the latter with Na2SS2OO4 gave dihydropyridine and dihydroquinoline compounds. The N--4-trifluorotoluidinonicotinate derivative was obtained from the coupling of niflumic acid and (±)-3TC using BOP and DIEA. The anti-HIV-1 activities of seven derivatives were determined in MT-4 infected cell cultures. Of these compounds, the IC0 v values ranged from 0.1–100 μM, while the IC0 f for (±)-3TC was 0.1 μM. The anti-HBV activities were determined in infected duck hepatocytes. Anti-HBV activities of the (±)-3TC derivatives were half that of the parent drug (±)-3TC. The lipophilicity (partition coefficients) of these compounds were determined. The dihydroquinoline prodrugs had greater lipophilicity than the dihydropyridine analogues.

Published
1996
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197. Natural recolonization of Pinus halepensis Mill, and Pinus pinaster Aitón in burnt forests of the Sierra de Al caraz-Segura mountain system (SE Spain)

Author

Jose-Maria Herranz, Juan J. Martínez-Sánchez, Juan Guerra, and Louis Trabaud

Subjects
Ecology, biology, Forestry, Vegetation dynamics, biology.organism_classification, Mediterranean vegetation, %22">Pinus , Forêts de Pinus halepensis et Pinus pinaster, recolonisation, feux sauvages, Geography, Wild Fires, Pinus pinaster, Pinus halepensis and Pinus pinaster forests, recolonization, wild fires, Ecology, Evolution, Behavior and Systematics
Abstract

The natural recolonization by Pinus halepensis Miller and Pinus pinaster Aiton after several fires between 1975 and 1985 has been studied, recording the density and cover of pines in relation to the cover of other species occurring in permanent plots. A comparison of burnt and unburnt plots showed poor recolonization of the pine groves owing to competition with other plants, except in a few sunny places where P. halepensis grew well and some shaded places where P. pinaster did well. Regeneration by pines was good only when fast growing species profusely resprouting or others producing many seeds were absent or infrequent., Recolonisation naturelle de Pinus halepensis Mill, et de Pinus pinaster Alton dans les forêts incendiées de la région des Sierras de Alcaraz-Segura (SE de l’Espagne). La recolonisation naturelle de Pinus halepensis Miller et Pinus pinaster Aiton après plusieurs incendies survenus entre 1975 et 1985 a été étudiée sur des parcelles permanentes en observant la densité et le recouvrement des pins en relation avec le recouvrement des autres espèces se régénérant. La comparaison des parcelles incendiées avec les parcelles non-incendiées a montré une faible recolonisation des pins due à la concurrence des autres végétaux ; toutefois , P. halepensis s ’est assez bien régénéré dans les endroits ensoleillés, tandis que P. pinaster réussissait mieux dans les sites ombragés. Une bonne régénération des pins n’apparaît que lorsque les autres espèces croissant rapidement et abondamment, soit par rejets soit par semences, sont absentes ou peu fréquentes., Martinez-Sanchez Juan Jose, Herranz Jose-Maria, Guerra Juan, Trabaud Louis. Natural recolonization of Pinus halepensis Mill, and Pinus pinaster Aitón in burnt forests of the Sierra de Al caraz-Segura mountain system (SE Spain). In: Ecologia mediterranea, tome 22 n°1-2, 1996. pp. 17-24.

Published
1996
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198. Failure and success of HIV tests for the prevention of HIV-1 transmission by blood and tissue donations

Author

Fatiha Najioullah, Marie-Anne Trabaud, Cathy Guitton, Jean-Claude Tardy, Patrice Andre, Nicole Coudurier, Valérie Barlet, Dominique Peyramond, Guérin Jc, Philippe Renaudier, and Philippe Crova

Subjects
Blood transfusion, medicine.medical_treatment, fungi, Biology, medicine.disease, biology.organism_classification, Virology, Residual risk, Infectious Diseases, Acquired immunodeficiency syndrome (AIDS), Tissue Donation, Nat, Immunology, Lentivirus, HIV p24 Antigen, medicine, Viral disease
Abstract

French blood banks recently implemented nucleic acid testing (NAT) of all blood donations to reduce the risk of HIV transmission during the pre-seroconversion period. For tissue donation, HIV infection screening relies on HIV p24 antigen and anti-HIV1 and 2 antibody detection. In this report, two related cases of infectious donations are described from a cornea donor during the preseroconversion window who was infected by an HIV antibody and NAT negative blood donor. After investigation, the blood donor was found to be herself in the preseroconversion window. Two months after donation, she was found to be HIV positive. The residual risk of HIV infectious blood donations since NAT has been introduced is estimated to be lower than one out of 2.5 millions. Individual NAT instead of minipool testing would not increase significantly the blood transfusion safety. In contrast, introduction of NAT should be considered to increase tissue donation safety as soon as such screening will be possible technically. J. Med. Virol. 73:347–349, 2004. © 2004 Wiley-Liss, Inc.

Published
2004
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199. Low-level viremia is associated with non-B subtypes in patients infected with HIV with virological success following HAART introduction

Author

Mary-Anne Trabaud, T. Ferry, P. André, Jean-Claude Tardy, J. Saison, René Ecochard, Christian Chidiac, Thomas Perpoint, Caroline Scholtes, Vinca Icard, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Adult, Male, Anti-HIV Agents, [SDV]Life Sciences [q-bio], HIV Infections, Viremia, Biology, 03 medical and health sciences, 0302 clinical medicine, Antiretroviral Therapy, Highly Active, Virology, medicine, Humans, In patient, Protease inhibitor (pharmacology), Prospective Studies, 030212 general & internal medicine, Prospective cohort study, 0303 health sciences, Univariate analysis, 030306 microbiology, Proportional hazards model, virus diseases, Middle Aged, Viral Load, medicine.disease, Virus Latency, 3. Good health, Regimen, Infectious Diseases, HIV-1, RNA, Viral, Female, Viral load
Abstract

This prospective study aimed to determine factors associated with detection of very low-level viremia in patients infected with HIV-1 with virological success following HAART introduction. Fifty-seven patients, mostly (n = 51, 89%) treated with a protease inhibitor-based regimen, were included and followed for 2 years. Viral loads were monitored by Abbott m2000 RealTime HIV-1. Patients were classified as (i) HIV-RNA-negative if viral loads remained strictly undetectable (0 copies/ml), or (ii) HIV-RNA-positive if at least one HIV-1 RNA could be detected in 1–49 copies/ml during follow-up. At month 24, 44 patients (77%) were in the HIV-RNA-positive group, whereas 13 (23%) remained without very low-level viremia. Univariate analysis, Kaplan–Meier curves and the Cox proportional hazard model revealed that B subtype was the only predictor of belonging to the HIV-RNA-negative group (HR 3.98; 95% CI 1.08–14.7). This association needs to be confirmed. Further study of the reservoir and the mechanisms of viral latency according to HIV-subtype will also be necessary to develop new therapeutic strategies and eradicate HIV infection. J. Med. Virol. 85: 953–958, 2013. © 2013 Wiley Periodicals, Inc.

Published
2013
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200. Synthesis of New Thiazolidinone Nucleoside Analogues

Author

V. Niddam, Nicolas Mourier, C. Trabaud, Viviana Simon, Michel Camplo, A. S. Charvet, P. Faury, Jean-Louis Kraus, and J. C. Graciet

Subjects
Coupling (electronics), Chemistry, Condensation, Genetics, Nucleic acid, Biochemistry, Nucleoside, Combinatorial chemistry
Abstract

The synthesis of new thiazolididone nucleoside analogues is described. Among the different proposed synthetic pathways, the condensation of various nucleic bases using TMSOTf and Et3N as coupling r...

Published
1995
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