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

Geological constraints on the evolution of the Angolan margin based on reflection and refraction seismic data (ZaïAngo project).

Deep penetration multichannel reflection and Ocean Bottom Seismometer wide-angle seismic data from the Congo–Angola margin were collected in 2000 during the ZaïAngo cruise. These data help constrain the deep structure of the continental margin, the geometry of the pre-salt sediment layers and the geometry of the Aptian salt layer. Dating the deposition of the salt relative to the chronology of the margin formation is an issue of fundamental importance for reconstructing the evolution of the margin and for the understanding of the crustal thinning processes. The data show that the crust thins abruptly, from a 30–40 km thickness to less than 10 km, over a lateral distance of less than 50 km. The transitional domain is a 180-km-wide basin. The pre-salt sediment layering within this basin is parallel to the base of the salt and hardly affected by tectonic deformation. In addition, the presence of a continuous salt cover, from the continental platform down to the presumed oceanic boundary, provides indications on the conditions of salt deposition that constrain the geometry of the margin at that time. These crucial observations imply shallow deposition environments during the rifting and suggest that vertical motions prevailed—compared to horizontal motions—during the formation of the basi

Numerical modelling of Cretaceous Pyrenean Rifting: The interaction between mantle exhumation and syn‐rift salt tectonics

International audienceThe preshortening Cretaceous Pyrenean Rift is an outstanding geological laboratory to investigate the effects of a pre‐rift salt layer at the sedimentary base on lithospheric rifting. The occurrence of a pre‐rift km‐scale layer of evaporites and shales promoted the activation of syn‐rift salt tectonics from the onset of rifting. The pre‐ and syn‐rift sediments are locally affected by high‐temperature metamorphism related to mantle ascent up to shallow depths during rifting. The thermo‐mechanical interaction between décollement along the pre‐existing salt layer and mantle ascent makes the Cretaceous Pyrenean Rifting drastically different from the type of rifting that shaped most Atlantic‐type passive margins where salt deposition is syn‐rift and gravity‐driven salt tectonics has been postrift. To unravel the dynamic evolution of the Cretaceous Pyrenean Rift, we carried out a set of numerical models of lithosphere‐scale extension, calibrated using the available geological constraints. Models are used to investigate the effects of a km‐scale pre‐rift salt layer, located at the sedimentary cover base, on the dynamics of rifting. Our results highlight the key role of the décollement layer at cover base that can alone explain both salt tectonics deformation style and high‐temperature metamorphism of the pre‐rift and syn‐rift sedimentary cover. On the other hand, in the absence of décollement, our model predicts symmetric necking of the lithosphere devoid of any structure and related thermal regime geologically relevant to the Pyrenean case