IMPATTO DI COBICISTAT SU DURATA ETOLLERABILITA¿ DI REGIMI ANTIRETROVIRALICONTENENTI TENOFOVIR DIPROXIL FUMARATO

INTRODUZIONE Il dosaggio di tenofovir alafenamide \ue8 stato ridotto da 25 a 10 mg al giorno quando somministrato con farmaci con funzioni di potenziatore. Tuttavia, tale riduzione del dosaggio non \ue8 mai stata adottata per tenofovir diproxil fumarato. Questo studio vuole valutare l'effetto di cobicistat sia sulle concentrazioni di tenofovir sia sulla durata del trattamento di un regime contenente tenofovir diproxil fumarato nella pratica clinica quotidiana. METODI Sono stati arruolati nello studio pazienti con infezione da HIV in terapia antiretrovirale contenente tenofovir diproxil fumarato con almeno una valutazione delle concentrazioni plasmatiche di tenofovir. Sono state condotte analisi di regressione uni- e multivariata considerando le concentrazioni di tenofovir come variabile dipendente e le caratteristiche cliniche come covariabili indipendenti. Le analisi di sopravvivenza e di Cox sono state effettuate considerando come evento primario l\u2019interruzione di tenofovir diproxil fumarato per qualsiasi ragione. RISULTATI 212 pazienti assumevano tenofovir diproxil fumarato con un inibitore della proteasi con ritonavir, 176 con un inibitore non nucleosidico, 46 con dolutegravir o raltegravir e 76 con elvitegravir/cobicistat. In analisi multivariata, sono risultati significativamente associati alle concentrazioni plasmatiche di tenofovir i farmaci antiretrovirali utilizzati in associazione, con le pi\uf9 alte concentrazioni misurate nei pazienti trattati con elvitegravir/cobicistat. Nell'analisi di sopravvivenza i pazienti trattati con tenofovir diproxil fumarato in associazione a elvitegravir/cobicistat presentavano la minor durata di trattamento con un rischio superiore di 2,3 volte di sospensione della terapia. CONCLUSIONI La cosomministrazione con cobicistat ha determinato concentrazioni di tenofovir significativamente pi\uf9 elevate e una maggiore interruzione del trattamento rispetto ad altri regimi. Di conseguenza, non pu\uf2 essere esclusa la possibilit\ue0 che il mancato aggiustamento del dosaggio di tenofovir diproxil fumarato quando associato a cobicistat possa aver pregiudicato il confronto di sicurezza rispetto a tenofovir alafenamide negli studi registrativiBACKGROUND The dose of tenofovir alafenamide is reduced from 25 to 10 mg daily when given with boosting agents. However, such dose reduction has never been adopted for tenofovir disoproxil fumarate. In this study we aim to quantify the effect of cobicistat both on tenofovir concentrations and tenofovir disoproxil fumarate durability in real life setting. METHODS HIV-positive patients receiving tenofovir disoproxil fumarate containing ART with at least one assessment of tenofovir plasma trough concentrations were included in the study. Uni- and multivariate regression analyses were carried out considering tenofovir concentration as the dependent variable and clinical characteristics as independent covariates. Subsequently, survival and Cox analyses were carried out considering as the primary outcome tenofovir disoproxil fumarate discontinuation for any reasons. RESULTS Patients were given tenofovir disoproxil fumarate with protease inhibitors/ritonavir (n=212), non nucleoside reverse transcriptase inhibitors (n=176), integrase inhibitors (DTG or RAL, n=46) or with elvitegravir/cobicistat (n=76). By multivariate analysis, concomitant antiretroviral therapies resulted significantly associated with tenofovir levels, with the highest drug concentrations measured in patients given elvitegravir/cobicistat. By survival analysis we found that patients given tenofovir disoproxil fumarate with elvitegravir/cobicistat had the lowest rate of drug durability. Overall, these patients had a 2.3-fold increased risk to experience tenofovir disoproxil fumarate discontinuation. CONCLUSIONS Coadministration with cobicistat resulted in significantly higher tenofovir concentrations and higher tenofovir disoproxil fumarate discontinuation compared with other antiretroviral regimens. Accordingly, the possibility that the lack of proper dose adjustment for tenofovir disoproxil fumarate when given with cobicistat might have biased the safety comparisons with tenofovir alafenamide during registrative trials cannot be ruled out

Supramolecular hierarchy among halogen and hydrogen bond donors in light-induced surface patterning

Halogen bonding, a noncovalent interaction possessing several unique features compared to the more familiar hydrogen bonding, is emerging as a powerful tool in functional materials design. Herein, we unambiguously show that one of these characteristic features, namely high directionality, renders halogen bonding the interaction of choice when developing azobenzene-containing supramolecular polymers for light-induced surface patterning. The study is conducted by using an extensive library of azobenzene molecules that differ only in terms of the bond-donor unit. We introduce a new tetrafluorophenol-containing azobenzene photoswitch capable of forming strong hydrogen bonds, and show that an iodoethynyl-containing azobenzene comes out on top of the supramolecular hierarchy to provide unprecedented photoinduced surface patterning efficiency. Specifically, the iodoethynyl motif seems highly promising in future development of polymeric optical and photoactive materials driven by halogen bonding

Effects of High Charge Densities in Multi-GEM Detectors

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Graphene is a single layer of carbon atoms arranged in a honeycomb lattice with remarkable mechanical and electrical properties. Regarded as the thinnest and narrowest conductive mesh, it has drastically different transmission behaviours when bombarded with electrons and ions in vacuum. This property, if confirmed in gas, may be a definitive solution for the ion back-flow problem in gaseous detectors. In order to ascertain this aspect, graphene layers of dimensions of about 2x2cm$^2$, grown on a copper substrate, are transferred onto a flat metal surface with holes, so that the graphene layer is freely suspended. The graphene and the support are installed into a gaseous detector equipped with a triple Gaseous Electron Multiplier (GEM), and the transparency properties to electrons and ions are studied in gas as a function of the electric fields. The techniques to produce the graphene samples are described, and we report on preliminary tests of graphene-coated GEMs.Comment: 4pages, 3figures, 13th Pisa Meeting on Advanced Detector

Towards a liquid Argon TPC without evacuation: filling of a 6 m^3 vessel with argon gas from air to ppm impurities concentration through flushing

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Fluorine-induced J-aggregation enhances emissive properties of a new NLO push–pull chromophore

A new fluorinated push–pull chromophore with good second-order NLO properties even in concentrated solution shows solid state intermolecular aryl–fluoroaryl interactions leading to J-aggregates with intense solid state luminescence