Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Altres ajuts: This study was sponsored by Janssen.Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52-96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917). Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis). Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis. Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF

Investigación de trihalometanos en agua potable del Estado Carabobo, Venezuela Trihalomethanes in the drinking water of Carabobo State, Venezuela

Objetivo: La desinfección del agua con cloro en las plantas de potabilización da lugar a la formación de trihalometanos (THM). Estos compuestos están asociados a efectos adversos para la salud. En este estudio se determinó la concentración de THM en el agua para consumo humano suministrada por las redes de distribución de los dos principales sistemas de potabilización de agua del Estado Carabobo, la planta Alejo Zuloaga y el embalse Pao-Cachinche que forman el Sistema Regional del Centro I (SRC-I) y la planta Lucio Baldo Soules y el embalse Pao-La Balsa que forman el Sistema Regional del Centro II (SRC-II). Métodos: Se analizaron un total de 144 muestras recolectadas durante 6 muestreos que se realizaron durante los años 2000 y 2001. La concentración de THM se determinó por cromatografía de gases, mediante la técnica de headspace. Se determinaron las concentraciones para los siguientes THM: cloroformo (CHCl3), bromoformo (CHBr3), dibromoclorometano (CHBr2Cl) y diclorobromometano (CHCl2Br). Resultados: La concentración de THM totales estuvo entre 47,84 y 93,23 &#956;g/l. El CHCl3 fue el compuesto predominante, representando el 83% de total de THM para el SRC-I y el 82% en el SRC-II. Se encontró que las concentraciones de THM totales en el SRC-I (Red Baja y Red San Diego) son significativamente superiores (p Objective: Disinfection of water with chlorine in water treatment plants leads to the formation of trihalomethanes (THMs). These compounds are associated with adverse health effects. The aim of this study was to analyze THM concentrations in the water provided for human consumption in the two main water treatment systems of Carabobo State: the Alejo Zuloaga plant and the Pao-Cachinche reservoir, which form the Central Regional System I (CRS I), and the Lucio Baldo Soules plant and the Pao-La Balsa reservoir, which form the Central Regional System II (CRS II). Methods: We analyzed 144 water samples collected in 6 samplings carried out in 2000 and 2001. THM concentrations were determined by gas chromatography using the headspace technique. The concentrations of the following THMs were measured: chloroform (CHCl3), bromoform (CHBr3), chlorodibromomethane (CHBr2Cl) and bromodichloromethane (CHCl2Br). Results: The concentration of total THMs was between 47.84 µg/l and 94.23 µg/l. CHCl3 was the most commonly formed compound representing 83% of all THMs in the CRS I and 82% in the CRS II. The concentrations of total THMs in the CRS I, specifically in the Baja and San Diego networks, were significantly higher (p < 0.05) than permissible levels set by the American Environmental Protection Agency (80 µg/l) for the sum of all four THMs. Conclusions: The results show that in the area studied there is a risk of adverse health effects due to THMs in drinking water, especially in the Baja and San Diego networks

Axial incision: The key to understand submarine canyon evolution (in the western Gulf of Lion)

A detailed morphological analysis of the outer shelf and continental slope of the Western Gulf of Lion is presented, based on swath bathymetry data together with sub-bottom profiles and high resolution seismic reflection profiles. These data reveal two main erosive features, of very different dimensions: the axial incision and the canyon's major valley. The height of axial incisions' flanks with respect to the canyon deepest point (the thalweg) ranges from 40 to 150 m. It creates a small axial erosive path within the canyon's major valley, which is typically bounded by flanks of more than 700 m in height. We interpret the axial incision observed in the sea floor as the imprint of turbidity currents that eroded the floor of canyons during phases of connection to rivers (hyperpycnal turbidity current). Such currents are most likely to have formed during the Last Glacial Maximum (LGM) as both proximity of the shoreline (due to the lowstand of sea level) and high detrital sediment supply (due to glacial abrasion upstream) increased the flow of sediments delivered to the canyon heads. Fossil axial incisions, observed in seismic lines, are related to equivalent conditions. The axial incision, however, has a key influence on canyon evolution as it triggers mass wasting of different sizes that affect the canyon's major valley (head and flanks). We interpret the geometry of the canyon's major valley as the result of recurrent activity of axial incisions. These periods of activity occurred during low sea levels at glacial maxima and show a cyclicity of 100,000 years for the last 400,000 years