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

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

Sedimentary sequences in the Gulf of Lion: A record of 100,000 years climatic cycles

The wide continental shelf of the Gulf of Lion (up to 70 km) has been the object of numerous investigations since the early days of oceanography. Yet, the question of sequences duration, the mechanisms of deposition and factors implied remained unanswered. A study of a very dense grid of Very High Resolution (VHR) seismic reflection (Sparker) data associated with surficial cores both, collected by IFREMER between 1992 and 2001 on the outer shelf and upper slope offshore of Sète in the Languedoc region gives a new insight into these issues. Analysis of the 3D geometry of the sedimentary record reveals a basic depositional pattern consisting of a pair of horizontally juxtaposed and downlapping prisms. Prism PI with low angle clinoforms (<1°) lies on the upper part of the shelf and is interpreted to be prodeltaic-offshore deposits. Prism PII with steeply dipping clinoforms (4°) lies on the outer shelf between 40 and 70 km from the present day coastline and is interpreted to be littoral deposits. Results obtained from integrating lithology, palynology, micropaleontology, seismic stratigraphy, stratigraphic simulation, support the hypothesis that the basic depositional pattern records a 100 000-years glacioeustatic (interglacial/glacial) cycle. As previously suggested by Aloïsi [Aloïsi, J.C., 1986. Sur un modèle de sédimentation deltaïque: contribution à la connaissance des marges passive, Thèse de Doctorat d'Etat. Université de Perpignan, 162 pp], prisms PI corresponds to deposition at high sea level and prisms PII to deposition during low sea level at glacial maxima. Five sequences of paired prisms capped by five major erosion surfaces have been identified and modelled showing that the corresponding glacioeustatic cycles (the last five cycles at least) are recorded on the shelf of the western part of the Gulf of Lio