Nevirapine versus Efavirenz for patients co-infected with HIV and Tuberculosis: A Randomised Non-Inferiority Trial

BACKGROUND: In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients. METHODS: We did a multicentre, open-label, randomised, non-inferiority trial at three health centres in Maputo, Mozambique. We enrolled adults (≥18 years) with tuberculosis and previously untreated HIV infection (CD4 cell counts <250 cells per μL) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal. 4-6 weeks after the start of tuberculosis treatment, we randomly allocated patients (1:1) with central randomisation, block sizes of two to six, and stratified by site and CD4 cell count to nevirapine (200 mg twice daily) or efavirenz (600 mg once daily), plus lamivudine and stavudine. The primary endpoint was virological suppression at 48 weeks (HIV-1 RNA <50 copies per mL) in all patients who received at least one dose of study drug (intention-to-treat population); death and loss to follow-up were recorded as treatment failure. The non-inferiority margin for the difference of efficacy was 10%. We assessed efficacy in intention-to-treat and per-protocol populations and safety in all patients who received study drug. This study is registered with ClinicalTrials.gov, number NCT00495326. FINDINGS: Between October, 2007, and March, 2010, we enrolled 285 patients into each group. 242 (85%) patients in the nevirapine group and 233 (82%) patients in the efavirenz group completed follow-up. In the intention-to-treat population, 184 patients (64·6%, 95% CI 58·7-70·1) allocated nevirapine achieved virological suppression at week 48, as did 199 patients (69·8%, 64·1-75·1) allocated efavirenz (one-sided 95% CI of the difference of efficacy 11·7%). In the per-protocol population, 170 (70·0%, 63·8-75·7) of 243 patients allocated nevirapine achieved virological suppression at week 48, as did 194 (78·9%, 73·2-83·8) of 246 patients allocated efavirenz (one-sided 95% CI 15·4%). The median CD4 cell count at randomisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine. 20 patients allocated nevirapine (7%) had grade 3-4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz (6%). Three patients had severe rash after receipt of nevirapine (1%) but no patients did after receipt of efavirenz. 18 patients in the nevirapine group died, as did 17 patients in the efavirenz group. INTERPRETATION: Although non-inferiority of the nevirapine-regimen was not shown, nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz. FUNDING: French Research Agency for HIV/AIDS and hepatitis (ANRS)

Articles Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial

Summary Background In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare effi cacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in coinfected patients

Stress rotations and the long-term weakness of the Median Tectonic Line and the Rokko-Awaji Segment

International audienceWe used a field analysis of rock deformation microstructures and mesostructures to reconstructthe long-term orientation of stresses around two major active fault systems in Japan, the Median TectonicLine and the Rokko-Awaji Segment. Our study reveals that the dextral slip of the two fault systems, activesince the Plio-Quaternary, was preceded by fault normal extension in the Miocene and sinistral wrenching inthe Paleogene. The two fault systems deviated the regional stress field at the kilometer scale in their vicinityduring each of the three tectonic regimes. The largest deviation, found in the Plio-Quaternary, is a more faultnormal rotation of the maximum horizontal stress to an angle of 79° with the fault strands, suggesting anextremely low shear stress on the Median Tectonic Line and the Rokko-Awaji Segment. Possible causes of thislong-term stress perturbation include a nearly total release of shear stress during earthquakes, a low staticfriction coefficient, or lowelastic properties of the fault zones comparedwith the country rock. Independently ofthe preferred interpretation, the nearly fault normal orientation of the direction of maximum compressionsuggests that the mechanical properties of the fault zones are inadequate for the buildup of a pore fluidpressure sufficiently elevated to activate slip. The long-term weakness of the Median Tectonic Line and theRokko-Awaji Segment may reside in low-friction/low-elasticity materials or dynamic weakening rather than inpreearthquake fluid overpressures

The discovery of I-BRD9, a selective cell active chemical probe for bromodomain containing protein 9 inhibition

Acetylation of histone lysine residues is one of the most well-studied post-translational modifications of chromatin, selectively recognized by bromodomain “reader” modules. Inhibitors of the bromodomain and extra terminal domain (BET) family of bromodomains have shown profound anticancer and anti-inflammatory properties, generating much interest in targeting other bromodomain-containing proteins for disease treatment. Herein, we report the discovery of I-BRD9, the first selective cellular chemical probe for bromodomain-containing protein 9 (BRD9). I-BRD9 was identified through structure-based design, leading to greater than 700-fold selectivity over the BET family and 200-fold over the highly homologous bromodomain-containing protein 7 (BRD7). I-BRD9 was used to identify genes regulated by BRD9 in Kasumi-1 cells involved in oncology and immune response pathways and to the best of our knowledge, represents the first selective tool compound available to elucidate the cellular phenotype of BRD9 bromodomain inhibition

Understand the structuring of wheat-legume cakes to promote product innovation and to design new formulation tools for the industry

Understand the structuring of wheat-legume cakes to promote product innovation and to design new formulation tools for the industry. Second International Legume Society Conferenc

Valoriser les associations céréale-légumineuse par la conception d’un produit nutritionnellement plus équilibré et de qualité maîtrisée : le projet FlexiProcess

Valoriser les associations céréale-légumineuse par la conception d’un produit nutritionnellement plus équilibré et de qualité maîtrisée : le projet FlexiProcess. Premières Rencontres Francophones Légumineuse

Impact de l’introduction de farine de légumineuse dans un produit céréalier courant

Impact de l’introduction de farine de légumineuse dans un produit céréalier courant. Premières Rencontres Francophones Légumineuse

Flexibilité de procédés de 2ème transformation de matières premières issues de cultures associées au champ et qualité nutritionnelle des cakes

Flexibilité de procédés de 2ème transformation de matières premières issues de cultures associées au champ et qualité nutritionnelle des cakes. Séminaire Carnots 3BCAR-Qualimen

Associer blé et légumineuses, du champ aux gâteaux moelleux : variabilité matières premières / modification des procédés / ingénierie reverse

International audienceThe cereal-legume combination has agronomic (less fertilizer and pesticide, increased productivity) and nutritional (protein profile more balanced than cereal only) benefits. To limit the energy consumption all along the sector, it can even be interesting to harvest and transform into flour the two types of seeds together. However, sowing, leading to the field and turning into flour without ever-separating wheat and legume leads to a large variation in the composition of mixed flours that must be managed to produce soft cakes of consistent quality. In the FlexiProcess project, we studied how the cake structure itself throughout the manufacturing process. We also analyzed the impact of mixed pea-wheat flour characteristics (grain size, legume / cereal proportion) on the cake softeness and on the cellular structure of the crumb. A multicriterion and multi-stress model was developed. It makes it possible to correct variations in the quality of the cakes induced by a variation in flour characteristics by modifying the mixing parameters of the ingredients and baking.L'association céréale-légumineuse présente des avantages aux niveaux agronomique (moins d'engrais et de pesticides, productivité accrue) et nutritionnel (profil protéique plus équilibré que la céréale seule). Pour limiter la consommation énergétique au long de la filière, il peut même être intéressant de récolter et transformer en farine les deux types de graines ensemble. Néanmoins, semer, conduire au champ, transformer en farine sans jamais séparer blé et légumineuse conduit à une grande variation de la composition des farines mixtes qu'il faut être capable de gérer pour produire des gâteaux moelleux de qualité constante. Dans le projet FlexiProcess, nous avons étudié la façon dont le gâteau se structure tout au long du procédé de fabrication et analysé l'impact de caractéristiques de farines mélangées pois-blé (granulométrie de la farine, proportion légumineuse/céréale) sur le moelleux des gâteaux et sur la structure alvéolaire de la mie. Un modèle multicritère et multi-contraintes a été développé. Il permet de corriger les variations de qualité des gâteaux induites par une variation de caractéristiques de farine en modifiant les paramètres de mélange des ingrédients et de cuisson au four. Abstract: Combine wheat and legumes, from the field to soft cakes: raw material variability / process modification / reverse engineering The cereal-legume combination has agronomic (less fertilizer and pesticide, increased productivity) and nutritional (protein profile more balanced than cereal only) benefits. To limit the energy consumption all along the sector, it can even be interesting to harvest and transform into flour the two types of seeds together. However, sowing, leading to the field and turning into flour without ever-separating wheat and legume leads to a large variation in the composition of mixed flours that must be managed to produce soft cakes of consistent quality. In the FlexiProcess project, we studied how the cake structure itself throughout the manufacturing process. We also analyzed the impact of mixed pea-wheat flour characteristics (grain size, legume / cereal proportion) on the cake softeness and on the cellular structure of the crumb. A multicriterion and multi-stress model was developed. It makes it possible to correct variations in the quality of the cakes induced by a variation in flour characteristics by modifying the mixing parameters of the ingredients and baking