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Background Maintenance ART with dolutegravir-based dual regimens have proved their efficacy among HIV-1-infected subjects in randomized trials. However, real-life data are scarce, with limited populations and follow-up. Objectives We assessed virological failure (VF) and resistance-associated mutations (RAMs) on dolutegravir maintenance regimens in combination with rilpivirine or with lamivudine or emtricitabine (xTC) and analysed the factors associated with VF. Methods Between 2014 and 2018, all HIV-1-infected adults included in the Dat’AIDS cohort and starting dolutegravir/rilpivirine or dolutegravir/xTC as a maintenance dolutegravir-based dual regimen were selected. VF was defined as two consecutive HIV RNA values >50 copies/mL or a single value >400 copies/mL. We compared cumulative genotypes before initiation of a maintenance dolutegravir-based dual regimen with genotype at VF. Results We analysed 1374 subjects (799 on dolutegravir/rilpivirine and 575 on dolutegravir/xTC) with a median follow-up of 20 months (IQR = 11–31) and 19 months (IQR = 11–31), respectively. VF occurred in 3.8% (n = 30) of dolutegravir/rilpivirine subjects and 2.6% (n = 15) of dolutegravir/xTC subjects. Among subjects receiving dolutegravir/rilpivirine, two genotypes harboured emerging RAMs at VF: E138K on NNRTI (n = 1); and E138K+K101E on NNRTI and N155H on INSTI (n = 1). Among subjects receiving dolutegravir/xTC, no new RAM was detected. The only predictive factor of VF on dolutegravir/rilpivirine was the history of failure on an NNRTI-based regimen (adjusted HR = 2.97, 95% CI = 1.28–6.93). No factor was associated with VF on dolutegravir/xTC. Conclusions In this large real-life cohort, dolutegravir/rilpivirine and dolutegravir/xTC sustained virological suppression and were associated with a low rate of VF and RAM emergence. Careful virological screening is essential before switching to dolutegravir/rilpivirine in virologically suppressed patients with a history of NNRTI therapy.

International audience; The objective of this cross-sectional survey was to assess the prevalence of psychoactive substance use (PSU) in people attending 11 French Sexual Transmitted Infection Centers, and to specify their profiles (PSU and link with risky sexual behaviors) using the ascending hierarchical clustering method. Among the 5220 individuals who completed the survey, 55.6% were men and the median age was 24 years [IQR: 20-31]. Among the participants, 2751 (52.7%) reported PSU at least once in their life. Ascending hierarchical clustering identified seven distinct profiles of participants based on their PSU. This study shows a high prevalence of PSU and alcohol consumption in this young population. Moreover, subgroup analysis allowed identifying groups of psychoactive substance users who presented specific risks or vulnerabilities and who should be priority targets for interventions, particularly sexual minority groups.

Objectives Screening, brief intervention and referral to treatment (SBIRT) is an evidence-based practice used to identify, reduce and prevent problematic use and abuse of, and dependence on, tobacco, alcohol and psychoactive substances. To date, the pertinence of this practice among people living with HIV (PLHIV) is unknown. In this pilot study, we aimed to assess the acceptability of SBIRT in a cohort of HIV-infected out-patients who were asked about their consumption of alcohol, tobacco and psychoactive substances. Methods A monocentric study was performed at the University Hospital of Montpellier. In a 6-month period, 20 trained physicians screened for the consumption of alcohol [using the Alcohol Use Disorders Identification Test (AUDIT)], tobacco (using the Short Fagerstrom Test) and psychoactive substances [using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) V3.0] via an auto-questionnaire and proposed a brief intervention to patients with misusage. Results One thousand and eighteen PLHIV completed the questionnaire, and 861 [84.6%; 95% confidence interval (CI) 82.2-86.7%] PLHIV returned it to the physician. Among the latter, 650 patients wished to discuss the answers with their physician (75.5%; 95% CI 72.5-78.3%), and brief interventions were realized in 405 patients (62.3%). Conclusions SBIRT is a simple screening and harm reduction tool that is well accepted by PLHIV in out-patient clinics. This method could be implemented in routine HIV care to screen and manage patients systematically for harmful substance use.

International audience; Background: Updated WHO guidelines recommend a dolutegravir-based regimen as the preferred first-line treatment for HIV infection and low-dose efavirenz (400 mg) as an alternative. We aimed to report the non-inferior efficacy of dolutegravir compared with efavirenz 400 mg at week 96.Methods: We did a multicentre, randomised, open label, phase 3 trial in in three hospitals in Yaoundé, Cameroon, in HIV-1 infected antiretroviral-naive adults with an HIV RNA viral load of greater than 1000 copies per mL to compare dolutegravir 50 mg with efavirenz 400 mg (reference treatment), both combined with lamivudine and tenofovir disoproxil fumarate. The primary endpoint was the proportion with a viral load of less than 50 copies per mL at week 48 (10% non-inferiority margin). The study is registered with ClinicalTrials.gov, NCT02777229 and is ongoing.Findings: Between July, 2016, and August, 2019, of 820 patients assessed, 613 were randomly assigned to receive at least one dose of study medication, with 310 in the dolutegravir group and 303 in the efavirenz 400 mg group. At week 96 in the intention-to-treat analysis, 229 (74%) of 310 patients receiving dolutegravir and 219 (72%) of 303 patients receiving efavirenz, achieved plasma HIV-1 RNA less than 50 copies per mL (difference 1·6%, 95% CI -5·4 to 8·6; p=0.66). Viral load suppression was reached significantly more rapidly in the dolutegravir group (p1000 copies per mL) was observed in 27 patients (eight in the dolutegravir group, among which, three women switched to efavirenz 600 mg because of the dolutegravir teratogeneicity signal, and 19 in the efavirenz 400 mg group). No acquired resistance mutations to dolutegravir were observed against 17 mutations to efavirenz with or without mutations to lamivudine and tenofovir disoproxil fumarate among the 19 efavirenz 400 mg participants with virological failure. Weight gain was greater in the dolutegravir group (median weight gain, 5·0 kg in the dolutegravir group and 3·0 kg in the efavirenz 400 mg group, p

International audience

Despite satisfactory efficacy of WHO-recommended second-line antiretroviral treatment for patients with HIV in low-income countries, the need for simplified, low-cost, and less-toxic maintenance strategies remains high. We compared boosted protease inhibitor monotherapy with dual therapy with boosted protease inhibitor plus lamivudine in patients on second-line antiretrovial therapy (ART).We did a multicentre, randomised, parallel, open-label, superiority, trial in the HIV services of five hospitals in sub-Saharan Africa (Yaoundé, Cameroon; Dakar, Senegal; and Bobo Dioulasso, Burkina Faso). We recruited patients from the long-term, post-trial cohort of the ANRS 12169/2LADY study that compared the efficacy of three second-line combinations based on boosted protease inhibitors. Participants for our study were HIV-1 infected with multiple mutations including M184V, at first-line failure, aged 18 years and older, on boosted protease inhibitor plus two nucleoside reverse transcriptase inhibitors (NRTI) for at least 48 weeks with at least 48 weeks follow-up in the 2LADY trial, with two viral load measurements of less than 200 copies per mL in the previous 6 months, CD4 counts of more than 100 cells per μL, adherence of at least 90%, and no change to ART in the past 3 months. We randomly assigned participants (1:1) to receive either monotherapy with their boosted protease inhibitor (once-daily darunavir 800 mg [two 400 mg tablets] boosted with ritonavir 100 mg [one tablet] or coformulation of lopinavir 200 mg with ritonavir 50 mg [two tablets taken twice per day]) or to boosted protease inhibitor plus once-daily lamivudine 300 mg (one 300 mg tablet or two 150 mg tablets). Computer-generated randomisation was stratified by study site and viral load at screening (50 copies per mL, and 50-200 copies per mL), and concealed from study personnel throughout the inclusion period. After randomisation, treatment allocation was not masked from clinicians or patients]. Patients had follow-up visits at weeks 4 and 12, and every 3 months until 96 weeks; if viral load exceeded 500 copies per mL at any visit, NRTI (tenofovir and lamivudine) were reintroduced into treatment. The primary outcome was the proportion of participants who had treatment failure at 96 weeks in the intention-to-treat analysis, where treatment failure was defined as one of the following: a confirmed viral load of more than 500 copies per mL, reintroduction of NRTI, or interruption of boosted protease inhibitor. We designed the study to detect a difference of 12% between groups in the primary outcome, with an expected 20% of patients having treatment failure in the monotherapy group. This study is registered with ClinicalTrials.gov, number NCT01905059.Between March 5, 2014, and Jan 26, 2015, 265 participants were assigned to receive monotherapy (133) or boosted protease inhibitor plus lamivudine (132). At week 48, an independent data safety monitoring board reviewed data, and advised discontinuation of the monotherapy group because the number of failures had exceeded the expected 20%; therefore results here are for week 48. At this point, treatment failure occurred in four (3·0%; 95% CI 0·8-7·6) of 132 participants on dual therapy and 33 (24·8%; 17·7-33·0) of 133 participants on monotherapy (relative risk 8·2, 95% CI 3·0-22·5; odds ratio 10·6, 95% CI 3·6-42·1). The difference between groups (21·8%, 95% CI 13·9-29·7; p0·0001) showed superiority of dual therapy compared with monotherapy. We recorded 46 severe adverse events of grade 3 or 4 (29 in the monotherapy group, 17 in the boosted protease inhibitor plus lamivudine group); one event in the montherapy group (intoxication resulting from co-administration of ritonavir-boosted lopinavir with an ergotamine derivate) was deemed related to study drug. Two participants in the monotherapy group and one in the dual therapy group died, all from causes not related to study drugs or procedures (one from complications from gastric cancer surgery, one in a work accident, and one from a lung disease of unknown cause).After viral suppression with boosted protease inhibitor plus NRTI in second-line ART, maintenance therapy with boosted protease inhibitor plus lamivudine was associated with a high rate of success, despite the presence of M184V mutations at first-line treatment failure. Results indicated that boosted protease inhibitor monotherapy cannot be recommended for these patients.Agence National de Recherche sur le Sida et les hépatites and Janssen Pharmaceutica.

Resume Objectif Decrire la prescription des traitements antifongiques systemiques en reanimation chez les patients adultes non neutropeniques. Patients et methodes Etude prospective, observationnelle, menee pendant le 1 er semestre 2010 dans les 7 services de reanimation d’un CHRU disposant de referents en anti-infectieux. Tous les patients adultes consecutifs non neutropeniques hospitalises en reanimation et recevant un traitement antifongique systemique pour une infection fongique invasive documentee ou suspectee, en dehors d’une aspergillose, etaient inclus. Resultats Parmi les 1502 patients admis en reanimation, 104 (7 %) recevaient un traitement antifongique dont 30 (29 %) pour une infection fongique documentee et 74 (71 %) pour une infection suspectee. Candida albicans etait isole dans respectivement 23 (77 %) des infections invasives et 45/52 (86 %) des colonisations broncho-pulmonaires et/ou urinaires au cours des infections suspectees. Une echinocandine etait significativement plus prescrite chez les patients avec une infection documentee (19/30 patients) et le fluconazole chez ceux avec une infection suspectee (48/74 patients). Le traitement de 1 re ligne etait principalement arrete pour guerison (11/30 patients) ou desescalade therapeutique (9/30 patients) au cours des infections documentees, et pour disparition d’indication (34/74 patients) ou guerison (21/74 patients) au cours des infections suspectees apres en moyenne 7 jours de traitement. Conclusion Dans notre centre, chez les adultes non neutropeniques en reanimation, un traitement antifongique etait administre dans deux tiers des cas pour une infection suspectee et non prouvee, le plus souvent par fluconazole. Les infections documentees etaient le plus souvent traitees par echinocandine avec desescalade secondaire. Une etude interventionnelle prospective evaluant la place des antifongiques en traitement pre-emptif ou empirique apparait necessaire.

International audience; Direct-Acting Antivirals (DAAs) opened a new era in HCV treatment. We report the impact of HCV treatment in French HIV-HCV coinfected patients. METHODS: All HIV-HCV patients from the Dat'AIDS cohort followed between 2012 and 2015 were included. HCV status was defined yearly as naive, spontaneous cure, sustained virological response (SVR12), failure or reinfection. RESULTS: Among 32,945 HIV-infected patients, 15.2% were positive for anti-HCV antibodies. From 2012 to 2015, HCV incidence rate increased from 0.35%PY to 0.69%PY in MSM, while median incidence was 0.08%PY in other patients. Median reinfection rate was 2.56%PY in MSM and 0.22%PY in other patients. HCV treatment initiation rate rose from 8.2% in 2012 to 29.6% (48.0% in pre-treated patients vs 22.6% in naïve patients). SVR12 rate increased from 68.7% to 95.2%. By the end of 2015, 62.7% of the patients were cured either spontaneously or following SVR. CONCLUSIONS: HCV treatment dramatically increased in HIV-HCV patients in France from 2012 to 2015 resulting in HCV cure in nearly two-thirds of the patients in this cohort. Combined with a declining HCV prevalence, the prevalence of active HCV infection among HIV patients will drastically decrease in the forthcoming years.

Overexpression of the Fc receptor CD64 on neutrophils is associated with innate immune response and bacterial infections. During HIV infection a large set of immune disorders including T-lymphocyte over-activation, microbial translocation, impairment of neutrophil functions, and immunodeficiency may interplay with neutrophil CD64 expression.Associations of neutrophil CD64 expression with CD8Higher neutrophil CD64 expression was observed in HIV infected subjects compared to healthy controls (0.91 vs. 0.75, P 0.001). Among 115 HIV infected patients, nine (8.8%) had a CD64 expression over the clinical threshold as calculated against bead standard (i.e., 1.5). HIV viremic patients were more likely to have an index above 1.5 (OR: 6.68, P values: 0.01). A trend for correlation between CD64 expression and CD8 T cell activation was observed (P values: 0.08). Blood CD4HIV infection and HIV replication are associated with up-regulation of neutrophil CD64. CD64 overexpression above the clinical threshold was observed in a minor proportion of HIV infected individuals treated by antiretroviral therapy and may be a marker of neutrophil activation related to non-AIDS-linked comorbidities. © 2016 International Clinical Cytometry Society.

The Clinical Laboratory Standards Institute ([CLSI] formerly NCCLS) reference broth microdilution testing method (protocol M27-A3) was compared with a commercially available methods (Sensititre YeastOne(®)) by testing two quality control strains and 102 isolates of Candida sp. and Cryptococcus sp. against fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole, flucytosin, amphotericin B and caspofungin. Minimal inhibitory concentrations (MIC) endpoints were determined after 24h of incubation for Sensititre YeastOne(®) and after 24 and 48 h for CLSI microdilution method. Essential agreements between methods vary from 70.6 to 92.2%. Categorical agreements vary from 94.1% for 5FC to 72.6% for AMB. Sensititre YeastOne(®) reading appears to be useful for avoiding very major errors and this confirms the interest of this method for evaluating new antifungals activity in vitro.

Les recentes donnees communiquees ou publiees sur le MVC en particulier chez les patients pretraites concernent le suivi jusqu'a S96 des patients inclus dans les essais MOTIVATE et l'essai randomise 1029 qui correspondait aux patients screenes en meme temps que MOTIVATE mais dont le virus avait un tropisme non R5 exclusif. Les essais MOTIVATE (1 et 2) concernaient des patients pour lesquels le virus avait un tropisme R5 (determine par le test trofile ® classique) avec une charge virale plasmatique (CVp) superieure a 5000 copies/ml. Ces patients ont recu soit un placebo soit du maraviroc (MVC), associe a un traitement optimise.

Resume Objectif Analyse de la conformite des traitements antifongiques instaures au cours de candidoses invasives en milieu de reanimation par rapport aux recommandations consensuelles francaises. Type d’etude Prospective, observationnelle, multicentrique francaise (octobre 2005–mai 2006). Patients et methodes Selection des patients presentant une candidose invasive au cours de laquelle la sensibilite des Candida sp. a ete documentee. Les traitements empiriques instaures avant la connaissance des donnees mycologiques et curatifs prescrits apres leur connaissance ont ete colliges. Leur conformite par rapport aux recommandations de la conference de consensus de 2004 sur le traitement des candidoses invasives de l’adulte a ete evaluee. Resultats Cent quatre-vingt-six patients ont ete etudies. Une candidose invasive liee a une ou plusieurs souches de Candida sp. resistant ou de sensibilite diminuee au fluconazole est retrouvee chez 18,3 % des patients, sans influence significative d’une exposition anterieure aux azoles. Les traitements etaient totalement conformes aux recommandations dans 47 % des cas. Les principales deviations etaient observees lorsque le traitement preconise etait l’amphotericine B qui a quasiment disparu de l’arsenal therapeutique en reanimation. Enfin, dans 16,9 % des episodes de candidoses pour lesquels le fluconazole etait le traitement empirique recommande, au moins une souche de Candida resistant ou de sensibilite diminuee a ce traitement etait isolee. Conclusion L’adhesion des reanimateurs aux recommandations de la conference de consensus de 2004 sur la prise en charge des candidoses invasives de l’adulte a ete observee pour 47 % des patients. La non-utilisation de l’amphotericine B quelle que soit sa forme galenique doit etre soulignee. L’observation d’une incidence non negligeable d’isolats de Candida de sensibilite diminuee ou resistant au fluconazole, en particulier chez les patients naifs de toute exposition anterieure aux azoles et l’impossibilite de la predire devraient conduire a envisager une actualisation des recommandations de 2004.

Resume Objectifs Le syndrome lipodystrophique du patient infecte par le VIH et la dyslipidemie qui l’accompagne sont ameliores par un reentrainement cible au premier seuil ventilatoire (Sv1), mais chez ces patients la signification metabolique de ce Sv1 n’est pas evidente. Nous avons tente de determiner les liens entre ce Sv1 et la calorimetrie d’effort et d’etudier les effets d’un reentrainement cible au niveau maximal d’oxydation des lipides (Lipoxmax) determine par cette derniere technique, sur ce tableau metabolique. Methodes Vingt et un sujets (trois femmes, 18 hommes, âge : 46,05 ± 1,7 ans, taille : 1,72 ± 0,02 m ; poids : 69,10 ± 2,47 kg), stables sur le plan immmunologique et therapeutique, ont beneficie d’une evaluation anthropometrique (impedancemetrie, coupe tomodensitometrique L4/L5), biologique et de l’aptitude physique au cours d’un test d’effort maximal avec determination des seuils ventilatoires et une calorimetrie indirecte d’effort pour mesurer l’oxydation des lipides et des glucides au cours de quatre paliers sous-maximaux de six minutes. Sur la base de ce dernier test dix sujets ont ete reentraines un an et retestes a l’issue de cette periode. Resultats Le point de croisement (PCX) definissant le niveau de passage a une utilisation majoritaire des glucides est abaisse a 43,47 ± 5,9 watts, soit 32,29 ± 4,4 watts en moyenne au dessous du Sv1 situe a 76,33 ± 5,5 watts. Le Lipoxmax est situe a 49,59 ± 4,53 watts. Si le Sv1 et le PCX sont bien correles (r = R = 0,762 ; p V O 2 max qui passe de 26,49 ± 1,36 a 31,13 ± 1,70 (p Discussion et conclusions Chez le HIV lipodystrophique, la calorimetrie d’effort montre une tendance a utiliser majoritairement, de facon precoce, les glucides, et le PCX semble etroitement lie au profil lipidique sanguin. Contrairement a la population generale, le seuil ventilatoire, dont l’interet en reentrainement a ete montre, ne coincide pas chez ces sujets avec le PCX. Le reentrainement en endurance cible par la calorimetrie d’effort semble avoir des effets analogues a ceux du reentrainement cible au Sv1 et notamment ameliorer nettement le bilan lipidique.

Resume Introduction L’incidence accrue des infections fongiques particulierement chez les patients neutropeniques pose de reels problemes de prise en charge therapeutique. En pediatrie, le manque de molecules antifongiques presentant une indication chez l’enfant ne fait qu’accentuer cette problematique. Objectif L’objectif de ce travail est de realiser un bilan des pratiques concernant l’utilisation des antifongiques en onco-hematologie afin d’elaborer des recommandations pertinentes au sein du CHU de Montpellier. Methodologie Cette etude retrospective a porte sur les patients hospitalises dans le service d’onco-hematologie pediatrique du CHU de Montpellier entre janvier 2003 et juillet 2005. Ces patients ont presente une infection fongique probable ou possible justifiant la mise en place d’un traitement antifongique, dans un contexte de neutropenie febrile. Resultats Les resultats obtenus montre le positionnement en premiere intention de l’Ambisome ® dans les infections probables ou possibles, le Cancidas ® etant positionne egalement en premiere intention dans les infections probables. Le VFend ® utilise en relais per os permet le maintien du controle de l’infection. Ces nouvelles specialites ont cependant un cout unitaire eleve. Conclusion Cette etude montre que les nouvelles molecules antifongiques sont devenues indispensables dans la prise en charge des infections fongiques car elles apportent un reel benefice d’un point de vue therapeutique.

International audience; There is no consensus on a diagnostic strategy for osteomyelitis underlying pressure ulcers. We conducted a prospective study to assess the accuracy of multiple bone biopsies and imaging to diagnose pelvic osteomyelitis. Patients with clinically suspected osteomyelitis beneath pelvic pressure ulcers were enrolled. Bone magnetic resonance imaging (MRI) and surgical bone biopsies (three or more for microbiology and one for histology per ulcer) were performed. Bacterial osteomyelitis diagnosis relied upon the association of positive histology and microbiology (at least one positive culture for non-commensal microorganisms or three or more for commensal microorganisms of the skin). From 2011 to 2014, 34 patients with 44 pressure ulcers were included. Bacterial osteomyelitis was diagnosed for 28 (82.3%) patients and 35 (79.5%) ulcers according to the composite criterion. Discrepancy was observed between histology and microbiology for 5 (11.4%) ulcers. Most common isolates were Staphylococcus aureus (77.1%), Peptostreptococcus (48.6%) and Bacteroides (40%), cultured in three or more samples in 42.9% of ulcers for S. aureus and ≥20% for anaerobes. Only 2.8% of ulcers had three or more positive specimens with coagulase-negative staphylococci, group B Streptococcus, and nil with enterococci and Pseudomonas aeruginosa. Staphylococcus aureus, Proteus and group milleri Streptococcus were recovered from one sample in 22.8%, 11.4% and 11.4% of ulcers, respectively. Agreement was poor between biopsies and MRI (κ 0.2). Sensitivity of MRI was 94.3% and specificity was 22.2%. The diagnosis of pelvic osteomyelitis relies on multiple surgical bone biopsies with microbiological and histological analyses. At least three bone samples allows the detection of pathogens and exclusion of contaminants. MRI is not routinely useful for diagnosis.

International audience

For long-life nuclear wastes (essentially actinides) research is in progress to develop new matrices with improved chemical durability. High-silica-content glasses possess a high chemical durability and we propose a new process to prepare silica glass which will embed the nuclear wastes. A porous network (silica aerogel) is used as a host matrix for nuclear wastes. The porous aerogel is soaked in a solution containing the actinides in nitrate salt form. After drying and nitrate decomposition, the composite material is fully sintered trapping the nuclear waste. Neodymium and cerium oxides are used to simulate the actinide oxides. A new kind of aerogel (composite aerogel) is proposed owing to its improved mechanical strength and relatively large permeability. A simple analysis of impregnation data is used to calculate the permeability. Increasing the bulk density from 0.4 to 1.4 g / cm 3 decreases the permeability from 200 to 20 nm 2 and increases the mechanical properties by two orders of magnitude. The influence of the porous network features (mechanical properties, mean pore size) on the ability of the material to soak up the simulating salts is discussed. This process allows the preparation of materials with a simulant content close to 20 wt%.

For long life nuclear wastes (essentially actinides) research is in progress to propose new matrices with an improvement of the chemical durability. High silica content glasses present high chemical durability, and we describe a process to prepare silica glass embedding the nuclear waste. Porous silica (gel) is used as a host matrix for nuclear waste. Neodymium oxide and cerium oxide are used to simulate the actinide oxides. The gel is soaked in a solution containing the simulant in nitrate salt form.

The density and the structure (fractal and non-fractal) of aerogels are modified either by the adjustment of the gelifying concentration, by a precise control of the viscous flow sintering process or by an isostatic pressure deformation. These aerogels have porosities ranging from 98% to 0%. The mechanical properties of the different aerogels (elastic modulus and strength) measured by 3 point bending, are dependent on their structure; they vary by five orders of magnitude as a function of density and follow power law evolution. However for the same relative density the elastic modulus and strength can increase by one order of magnitude due to a change in connectivity. These structural differences have been observed by SAXS experiments. The effects of the sintering process compared to that of the plastic transformation on the mechanical properties are explained by the associated structural changes. Sintering increases the network connectivity and the densification by compression leads to a new spatial arrangement of the clusters but their internal structure is not affected. In addition, relationships between structural and porous features and the mechanical properties are discussed in terms of percolation theory and the fractal approach. We show that the exponent of the power law does not depend on the fractal feature and percolation is only an approximation which cannot describe results.

An approach to nuclear waste fixation is to incorporate radioactive elements in multicomponent oxide glasses containing silica, alumina, boron and alkali. For long-lived nucleides, a new alternative approach is considered in order to evaluate durability of new matrices. High silica glasses present high chemical durability and stability associated with strength and thermal shock resistance. A process is described in which a porous, partially sintered silica aerogel is used as a host matrix for actinides. The porous aerogel is soaked in a solution containing the wastes in nitrate salt form. Neodymium oxide is used to simulate the actinide oxides. We investigate the effect of the porous network features (mechanical strength, pore size) on the ability of the material to soak up the simulating salts. Composite materials (silica glass+simulating oxide) have been synthesized with Nd 2 O 3 content close to 10 wt%.

International audience; Evaporite sediments are known to have formed during the Messinian high salinity crisis that has been recognized in many Mediterranean areas. This event was however never identified on the Maltese Islands. In this study, a Sr isotopic characterization of gypsum, found as secondary minerals in the Oligocene-Miocene formations of Malta and Gozo is performed. The 87Sr/86Sr values are discussed on the basis of comparison with the surrounding rock Sr isotopic signature. The data outline two distinguishable 87Sr/86Sr ratios for gypsum according to their facies. Most of crack-infilling mineral data suggest a downward fluid circulation in the Miocene sediment associated with interaction in the currently outcropping limestones. Some gypsum crystals found as crystallized spherules show significantly lower 87Sr/86Sr ratios, close to those defined in the literature for Messinian evaporate sediments. Taken together, this may suggest that an evaporate formation of Messinian age had in the past covered the present-day sedimentary sequence in Malta and Gozo.

Describe systemic antifungal therapy in non-neutropenic adult patients in intensive care unit (ICU).A prospective, observational study was conducted during the first half of 2010 in the 7 ICU in a hospital with medical consultant on antimicrobial therapy. All non-neutropenic consecutive adult patients receiving systemic antifungal therapy for documented or suspected invasive fungal infection (IFI) apart from aspergillosis were included.Out of 1502 patients admitted in ICU, 104 (7 %) underwent systemic antifungal therapy, including 30 (29 %) for a documented IFI and 74 (71 %) for a suspected IFI. Candida albicans was identified in 23 (77 %) of the IFI and 45/52 (86 %) of the broncho-pulmonary and/or urinary colonizations in suspected IFI. Echinocandin was significantly more prescribed in patients with a documented infection (19/30 patients) and fluconazole in patients with a suspected infection (48/74 patients). The first line therapy was primarily stopped after recovery (11/30 patients) or de-escalation (9/30 patients) in documented infections, and for lack of indication (34/74 patients) or due to recovery (21/74 patients) in suspected infections after on average of 7 days of treatment.For ICU non-neutropenic adult patients in our center, antifungal therapy is prescribed two times out of three for suspected, unproved infections, in most cases with fluconazole. Documented infections were more often treated by echinocandin with secondary de-escalation. An interventional prospective study to assess the role of antifungal pre-emptive or empirical therapy is necessary.

International audience; Nanocomposite aerogel is proposed as a host matrix for the synthesis of glass ceramics. The large porosity is used as a sponge to incorporate chemical species getting a two phases material. We describe the steps of the synthesis of glass ceramics for nuclear waste containment, from nanocomposite aerogels loaded with actinides surrogates (Ce and Nd). The glass synthesis is obtained without melting, by a control of several solid phase transformations: sintering, viscous flow, crystallization and foaming. Thanks to their high resistance to thermal shock and water corrosion, these glass ceramics are certainly good candidates as actinides containment materials.

To ensure long-term storage, long-life nuclear wastes (actinides) must be incorporated in a matrix exhibiting excellent chemical durability. Among the usual glasses, silica glass, which does not contain alkali and boron, is expected to present high durability. Associated with good mechanical properties, a low thermal expansion, and consequently a good thermal shock resistance, silica glass is a promising candidate. However, the glass preparation requires a high temperature (1,800°C) melting process. Nevertheless, silica glasses can be synthesized from silica aerogels followed by a sintering in a temperature range (1,000°C) close to half of that of the glass melting process. The impregnation of aerogels by actinide solutions followed by aerogels sintering has been proposed. After sintering, the aerogel silica matrix traps the nuclear waste and protects them against water erosion. The resulting material is a nanocomposite material (glass-ceramic) composed of nuclear wastes embedded in the silica matrix. The dissolution rate of such a composite in water is almost 102 times lower than that of the common nuclear glasses. This result clearly proves the improvement of the chemical durability of the glass-ceramic made from aerogels and, thanks to the high mechanical properties, these new materials can be suitable matrices for the containment of actinides. This contribution describes the different steps of the gel–aerogel–glass transformations and the characterization of the durability and mechanical properties of such glass- ceramics trapping the nuclear waste. The interest of silica aerogel as host matrix for nuclear waste containment is emphasized.

The aim of the study was to compare the metabolic and morphological effects of enfuvirtide plus an optimized background (OB) regimen vs. OB alone (control group) in treatment-experienced patients in the T-20 vs. Optimized Regimen Only (TORO) studies.Body composition and metabolic changes were investigated in patients over 48 weeks, based on fasting chemistries, body weight, and other anthropometric measurements. Dual-energy X-ray absorptiometry (DEXA) and computed tomography (CT) scans were performed in a patient subgroup (n=155) at baseline and at weeks 24 and 48.At week 48, mean changes from baseline were similar between treatment groups for glucose, insulin, C-peptide, total cholesterol, low-density lipoprotein (LDL) cholesterol, very low density lipoprotein (VLDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglyceride levels. The enfuvirtide group experienced a significant increase in body weight [mean change from baseline +0.99 kg; 95% confidence interval (CI) +0.54, +1.44] and, in those who had body scans, there was a significant increase in truncal fat (by DEXA: median change +419.4 g; 95% CI+71.3, +767.5) and total fat [visceral adipose tissue (VAT)+subcutaneous adipose tissue (SAT) by single-slice abdominal CT scan: median change +25.5 cm(2) ; 95% CI+8.9, +42.0] over 48 weeks; significant increases in these parameters were not seen in the control group. There was no significant change in truncal:peripheral fat ratio in either the enfuvirtide or the control group.The addition of enfuvirtide to an OB regimen does not appear to have unfavourable effects on fat distribution or metabolic parameters.

The authors had for objective to assess systemic antifungal treatment for candidemia in non-neutropenic patients, in intensive care units (ICU), and compare the results with French 2004 recommendations.A retrospective multicenter study (nine ICU in two teaching hospitals) was made.Thirty-eight non-neutropenic patients with at least one positive blood culture for Candida who had received systemic antifungal treatment were included between May 2004 and September 2007.Thirty-nine cases of candidemia were analyzed. The median age was 54.5 (21-80), the median SAPS II score at admission was 44 (20-79), the median duration of stay in ICU was 22.5 days (2-82), and the death rate was 45%. Candida albicans was identified in 69% of the cases. Eight percent of Candida sp. isolates were resistant or susceptible dose-dependent (S-DD) to fluconazole. Before identification, fluconazole, caspofungin, voriconazole, and amphotericin B were used in 74%, 15%, 5%, and 5% of cases respectively. After identification and antifungal susceptibility determination, fluconazole was used in 68% of cases, caspofungin in 24% of cases, any formulation of amphotericin B in 6% of cases, voriconazole in 3% of cases. The French recommendations were applied in 71% of cases before identification and in 68% of cases after identification and antifungal susceptibility determination.The main causes of non-compliance to recommendations were the use of fluconazole in patients previously exposed to azole agents, the use of caspofungin in hemodynamically unstable patients, and the absence of therapeutic desescalade.

Resume Chez cinq malades atteints du syndrome d'immuno-deficience acquise (sida) et indemnes de neuropathie peripherique, des symptomes musculaires (faiblesse, amyotrophie, douleurs et crampes) ou une elevation isolee des enzymes seriques ont ete constates. L'examen electromyographique (EMG) a permis de retrouver chez tous les malades des activites spontanees de fibrillations (f) et de potentiels lents (pl) et chez deux, des traces a signification myogene. La biopsie musculaire etait normale dans trois cas; l'aspect etait celui d'une myopathie dans un cas et d'une polymyosite dans l'autre. Dans un cas, les reactions immunocytochimiques ont mis en evidence des alterations de la dystrophine et de la laminine. La signification de ces alterations est discutee ainsi qu'une possible relation entre les activites spontanees et les modifications des proteines membranaires.

Cryptococcosis is the most common life-threatening opportunistic fungal infection in patients with AIDS; meningitis and meningoencephalitis are the most frequent manifestations. Meningoradicular involvement is exceptional. We report a case of meningoradiculitis due to Cryptococcus appearing after several weeks of antiretroviral and antifungal treatments, managed by corticosteroids, and which was suggestive of immune reconstitution inflammatory syndrome (IRIS). ### Case report. A 32-year-old HIV-infected man presented with a 7-day history of intense headache and vomiting. On admission, he was afebrile and examination was normal (no radicular symptoms). Evaluation of CSF showed no white cells, a moderately elevated total protein (490 mg/L), and normal glucose levels (3 mmol/L). The intracranial pressure was 34 cm H2O. Smear and cultures for bacteria and acid-fast bacilli were negative. An India ink preparation of the CSF revealed encapsulated yeast-like fungi, and Cryptococcus neoformans variety grubii was isolated. The C neoformans antigen latex agglutination test showed elevated titers in both serum (1:16,000) and CSF (1:8,000). The CD4 cell count was 97/μL and viral load was 454 copies/mL. Treatment including IV liposomal amphotericin B (3 mg/kg per day) and flucytosine (100 mg/kg per day) was started, associated with external lumbar derivation for severe intracranial pressure. Highly active antiretroviral therapy was begun 2 weeks after antifungal treatment (abacavir/lamivudine with lopinavir/ritonavir). However, the patient’s consciousness level progressively deteriorated, the trachea was intubated, and he was transferred to the intensive …

The authors had for aim to assess the conformity of antibiotic prescription with guidelines, for the management of community-acquired pneumonia, in a French University Hospital.This prospective study included adults patients hospitalized for pneumonia over a period of six months. The attending physician estimated the severity of pneumonia. The adequacy to guidelines focused on: first antibiotic choice and prescription modality, antibiotic choice in case of treatment modification at 48 to 72 hours, and duration of antibiotherapy.A hundred and nine cases of pneumonia were included in 106 patients. The mean age was 66 years, the mortality rate was 17 %. Bacterial documentation was recorded in 40.4 % of cases. The first antibiotics used were in accordance with guidelines in 52.3 % of cases. The non conformity rate was minor in 55.8 % of cases. Antibiotherapies putting the patient at risk were used in less than 10 % of the cases. The rate of antibiotic modification at 48 to 72 hours was 46.8 %, primarily for bacteriological purposes (35.3 %) or initial treatment failure (27.4 %). The treatment duration was inappropriate in 52.7 % of cases and generally too long in case of non conformity.It seems important to support guideline information, training of prescribers, and to consult an antibiotic expert.

Misuse of high-dose buprenorphine (HDB), mainly by injection, is responsible of frequent infectious adverse events.This is a retrospective study of infectious complications occurring in patients using HDB by injection. Forty-two cases were identified (29 men and ten women) and the data were collected between March 1999 and December 2008.The infectious complications included cutaneous infections (27 cases), endocarditis (nine cases), osteoarticular infections (four spondylodiscitis and one sacroiliitis), and a vascular embolism with decrease in visual acuity.The results of HDB maintenance treatment must be improved, both from the point of view of substitution and to limit its misuse by intravenous route injection. Health professionals have to play an important role in drug addict patients' education and supervision, to prevent buprenorphine injection and related infectious complications.

Comparison of treatments initiated during invasive candidiasis in intensive care units with current French guidelines.Prospective, observational, French multicenter study (October 2005-May 2006).Selection of patients with Candida species identification and in vitro antifungal susceptibility determination. The empiric treatments instituted before the microbiologic documentation of infection and the curative treatments instituted after identification of the causative Candida and determination of its susceptibility were collected and compared with treatments proposed by the French clinical practice guidelines (2004) for the management of patients with invasive candidiasis.One hundred and eighty-six patients were studied. Invasive candidiasis was due to fluconazole-resistant or susceptible-dose dependent Candida in 18.3% of patients, without any significant influence of a previous treatment with azoles. Empiric and curative treatments were both in accordance with recommendations for 47% of patients. Recommendations were mainly not respected when proposed therapy was amphotericin B that disappeared from therapeutics used in ICU. Finally, 16.9% of episodes of invasive candidiasis, for which fluconazole was the recommended treatment, were due to fluconazole-resistant or susceptible-dose dependent Candida.The support of French ICU physicians to current French guidelines was observed in 47% of cases. The infrequent use of amphotericin B must be emphasized. The nonnegligible incidence of fluconazole-resistant or susceptible-dose dependent Candida sp., particularly in patients without any prior exposition to azole agents, and the inability to predict this resistance should lead to propose a revision of 2004 guidelines.

Inhibition of CCR5 co-receptor which is also a chemokine receptor, is a new way for inhibition of HIV-1 replication. Small antagonist molecules exert non competitive inhibition of the HIV co-receptor CCR5, which is essential for HIV entry. The CCR5 antagonists aplaviroc (GlaxoSmithKine), vicriviroc (Schering-Plough), and maraviroc (Pfizer) have reached phases III of clinical development. The development of aplaviroc was stopped because of its hepatotoxicity in some of the HIV-infected patients. In ACTG 5211 and MOTIVATE trials, treatment-experienced subjects who added respectively vicriviroc and maraviroc demonstrated substantially greater reductions in plasma HIV-1 RNA levels than those who received the placebo ; maraviroc currently having obtained European authorization. The place of this new class in the strategies of initial, switch or rescue treatment remains to be clarified. The limitations of the use of these small molecules depend on their mechanism of action : obligation for monitoring the evolution of coreceptor usage, risk of failure by emergence of pre-existing strains with CXCR4 (X4) tropism or by resistant strains with CCR5 tropism, potential risks related to blocking of the physiological functions of this chemokine receptor.

Bartonella henselae is the etiologic agent of the cat scratch disease and in immunocompromised patients, of bacillary angiomatosis and peliosis hepatis. Less often, ocular complications associated with B. henselae infection have been reported in immunocompetent patients and five times in HIV-infected patients. We report the case of a 42-year-old woman, coinfected by HIV-HCV, presenting with cirrhosis, who owned a cat and was hospitalized for bilateral loss of visual acuity. Ophthalmologic examination revealed bilateral papillitis with hyalitis. Nuclear magnetic resonance revealed a retrobulbar neuritis. Confirmation was given by blood tests positive for B. henselae and the exclusion of other causes of neuroretinitis with biological data. Doxycycline cured the disease rapidly.

The aim of this work is to show to what extent a psychosocial evaluation can lead bring to comprehension of the subjectivity of Quality of Life (QoL) among HIV-infected patients. Evaluation of QoL makes it possible to understand the link between the therapeutic effectiveness and the subjective evaluation of the treatment, but also to estimate more precisely how people live and take their treatment in the context of HIV infection.This work confronts the variation of QoL with the variation of several social and psychosocial parameters identified as of the components of the system, which is the subjective evaluation, and more precisely to a specific side effect of Highly Active AntiRetroviral Therapies (HAART): lipodystrophy syndrome that consists in body fat redistribution. This side effect could consist in an accumulation of body fat, or a loss of body fat or a combination of both symptoms. The analysis was made on the data from APROCO-COPILOTE cohort composed of HIV-infected patients initiating HAART.Among a sample of 706 patients follow-up for three years and with available QoL data, we identified the variations of QoL according to the variation of this specific side effect and according to gender. Results show that lipodystrophy syndrome has a determinant impact on QoL different among male and female patients. Adjusted on clinical and socio-demographic characteristics, impaired women's QoL is associated with accumulation of body fat and impaired men's QoL is associated with loss of body fat.These results underline the role of body image on subjective evaluation of QoL. The analysis of empirical data made it possible to highlight the social implication of the evaluation of QoL from the role of the social support, patient-provider relationship and the social context.

Ce travail vise a montrer ce qu’une evaluation psychosociale peut apporter a la comprehension de la subjectivite de la qualite de vie (QDV) des patients infectes par le VIH. Les analyses se sont appuyees sur les donnees de la cohorte APROCO-COPILOTE, incluant des patients infectes par le VIH initiant une multitherapie antiretrovirale. Ces nouvelles therapies ont engendre, pour de nombreux patients, un type particulier d’effet indesirable : les lipodystrophies qui se caracterisent par des troubles de repartition de la masse graisseuse. L’objectif de ce travail est de determiner les liens entre l’apparition de ce type d’effets indesirables et la QDV des personnes infectees par le VIH en distinguant selon qu’il s’agisse d’hommes ou de femmes. Les analyses effectuees sur un echantillon de 706 patients (ANCOVA) mettent en evidence un impact important mais different des effets indesirables de type lipodystrophies sur la QDV et cela selon le type d’atteinte : lipodystrophie (accumulation) ou lipoatrophie (absence de graisse) et le sexe de la personne touchee. Il apparait que, ajustee sur les caracteristiques socio-demographiques et psychosociales, la QDV des femmes est davantage affectee par les lipodystrophies alors que pour les hommes il s’agit avant tout des lipoatrophies. Ces resultats, interpretes au regard de la theorie corporo-sociopsychologique, montrent les implications determinantes de ces effets indesirables quant a la QDV des patients infectes par le VIH. L’analyse des donnees empiriques a permis de mettre en evidence l’ancrage societal de l’evaluation de la QDV de par le role de l’entourage social, des soignants et du contexte social.

The most frequent side-effects due to nevirapine (Viramune), the first non-nucleoside HIV reverse transcriptase inhibitor introduced for clinical use, are cutaneous hypersensitivity reactions. In non-serious cases, tolerance induction can be proposed.Describe the long-term safety and efficacy of tolerance induction to nevirapine.Six HIV-infected patients started a tolerance 1 to 2 months after an episode of nevirapine hypersensitivity. Increasing doses of nevirapine (2.5, 10, 25, 100, 250 and 750 microg and 2.5, 5, 10, 25, 50 and 100 mg) were given orally at half-hour intervals under strict medical surveillance and patients were followed up regularly.All but two of the patients tolerated this induction well. One had a mild and transient reaction on day 1; nevirapine was not stopped. One had a moderate to severe reaction one month later; nevirapine was stopped and he recovered fully. All other patients have been taking nevirapine for more than 3 months without any adverse reaction.Therefore, when no alternatives are available in severely ill and hypersensitive HIV-infected patients, tolerance induction is a possible therapeutic option.

Using results of a multicentric randomized prospective trial of primary prophylaxis of Pneumocystis carinii pneumonia in HIV-infected patients which compared sulfamethoxazole-trimethoprim and pentamidine isethionate, the risk to develop cerebral toxoplasmosis was analyzed in the two assigned groups and in the groups of patients who stopped sulfamethoxazole-trimethoprim prophylaxis. The risk to develop cerebral toxoplasmosis appeared significantly higher in the group of patients who stopped sulfamethoxazole-trimethoprim consecutively to cutaneous hypersensitivity.

To describe and analyze the clinical and biological manifestations of thrombotic microangiopathy (TMA) and evaluate the therapeutic strategies.A retrospective study was performed in 14 infectious diseases units of southern France. All HIV patients presenting TMA during the last decade were selected (n = 14).The principle signs observed, aside from defining TMA (association of microangiopathic hemolytic anemia, thrombocytopenia and renal failure), were diarrhea (n = 9) and a high level of lacticodehydrogenase (LDH). Patients were at an advanced stage of HIV infection (median of CD4+ cells counts = 70/mm3). Specific etiology was identified in 7 cases: bacterial infection (n = 5), CMV retinitis associated with Kaposi's sarcoma (n = 1) and intravenous drug use (n = 1). Various treatments were used: plasmatic exchange (5 cases), fresh frozen plasma (6 cases), steroid therapy (4 cases), acetyl salicylic acid (3 cases), adaptation of antiretroviral treatment (3 cases). The global prognostic was poor with 50% mortality within 2 months. A high level of LDH (2500 UI/L) was associated with premature death in 5 of the 6 cases observed.Our data confirm the severity of TMA in case of HIV infection. The common treatment remains the use of plasmatic exchange and fresh frozen plasma; an optimal antiretroviral therapy must be associated.