The Experts below are selected from a list of 24714 Experts worldwide ranked by ideXlab platform
Christian Callebaut - One of the best experts on this subject based on the ideXlab platform.
-
rare emergence of drug resistance in hiv 1 treatment naive patients receiving elvitegravir cobicistat emtricitabine tenofovir alafenamide for 144 weeks
Journal of Clinical Virology, 2018Co-Authors: Nicolas A Margot, Scott Mccallister, Michael D Miller, Christian CallebautAbstract:Abstract Background The single tablet regimen (STR) composed of elvitegravir (E), cobicistat (C), emtricitabine (F), and tenofovir alafenamide (TAF) (E/C/F/TAF) was compared to the STR composed of E, C, F, and tenofovir disoproxil fumarate (TDF) (E/C/F/TDF) in 2 phase 3 studies in 1733 HIV-1 infected treatment-naive adults. Superior efficacy of E/C/F/TAF compared to E/C/F/TDF was demonstrated at Week 144 with 84% treatment success compared to 80%, respectively, along with significantly better outcomes of bone and renal safety. Objectives Analyze the emergence of HIV-1 resistance in treatment-naive adults receiving E/C/F/TAF for 144 weeks. Study design We conducted an integrated resistance analysis of the 2 Phase 3 studies, comprising pretreatment HIV-1 sequencing for all participants (N = 1733) and post-baseline HIV-1 resistance analysis for participants with virologic failure (HIV-1 RNA ≥400 copies/mL). Results Primary resistance-associated mutations (Rams) were observed pre-treatment in 7.4% (NRTI-Rams), 18.1% (NNRTI-Rams), and 3.3% (PI-Rams) of enrolled subjects. Baseline HIV-1 subtype or pre-existing Rams did not affect E/C/F/TAF treatment response at week 144. Virologic failure resistance analyses were conducted for 28/866 (3.2%) and 30/867 (3.5%) patients in the E/C/F/TAF and E/C/F/TDF arms, respectively. Over the 3-year study, the rate of resistance emergence remained low at 1.4% in each group (12/866 in E/C/F/TAF; 12/867 in E/C/F/TDF). Resistant virus emerged in 24 patients who developed resistance to antiretrovirals in the regimens (E/C/F/TAF: M184V/I [1.3%], INSTI-Rams [0.9%], K65R/N [0.2%]; E/C/F/TDF: M184V/I [1.0%], INSTI-Rams [0.9%], K65R/N [0.5%]). Conclusions Resistance emergence was rare (1.4%) with similar patterns of emergent mutations in both groups. M184V/I was the most prevalent RAM (1.2% overall).
-
infrequent development of drug resistance in hiv 1 infected treatment naive subjects after 96 weeks of treatment with elvitegravir cobicistat emtricitabine tenofovir alafenamide or elvitegravir cobicistat emtricitabine tenofovir disoproxil fumarate
Antiviral Therapy, 2017Co-Authors: Nicolas A Margot, Scott Mccallister, Michael D Miller, Stephanie Cox, Moupali Das, Christian CallebautAbstract:BACKGROUND Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide reverse transcriptase inhibitor tenofovir (TFV) that loads lymphocytes with TFV-diphosphate more efficiently than tenofovir disoproxil fumarate (TDF). The single-tablet regimen (STR) comprising elvitegravir, cobicistat, emtricitabine and TAF (E/C/F/TAF) has demonstrated non-inferiority to the STR of E/C/F/TDF in clinical studies, with high proportions of subjects achieving HIV-1 RNA <50 copies/ml at week 48 that were maintained through week 96. A resistance analysis of the combined Phase III clinical studies through 96 weeks is described here. METHODS Genotypic and phenotypic susceptibility to antiretrovirals (ARVs) was evaluated for subjects with HIV-1 RNA ≥400 copies/ml at time of virological failure (VF) or early discontinuation. RESULTS Through week 96, VF resistance analyses were conducted for 24 subjects in each arm (2.8%, 24/866 and 2.8%, 24/867; for E/C/F/TAF and E/C/F/TDF arms, respectively). Primary resistance development to ARVs of the regimen occurred in 10 of 24 subjects in the E/C/F/TAF arm, and 8 of 24 subjects in the E/C/F/TDF arm (E/C/F/TAF: M184V/I, n=9; integrase strand-transfer inhibitor resistance-associated mutations [INSTI-Rams], n=8; K65R/N, n=2; E/C/F/TDF: M184V/I, n=6; INSTI-Rams, n=5; K65R/N, n=3). The emergent resistance mutations were similar between the treatment arms. CONCLUSIONS E/C/F/TAF achieved a high level of virological suppression in HIV-1 treatment-naive subjects through 96 weeks of treatment, with infrequent resistance development and comparable genotypic changes across both the E/C/F/TAF and E/C/F/TDF treatment groups.
Hansulrich Schmincke - One of the best experts on this subject based on the ideXlab platform.
-
boundary conditions for damming of a large river by fallout during the 12 900 bp plinian laacher see eruption germany syn eruptive rhine damming ii
Journal of Volcanology and Geothermal Research, 2020Co-Authors: Cornelia Park, Hansulrich SchminckeAbstract:Abstract The Rhine River (Germany) - the largest river in Western Europe - was dammed by pyroclastic material multiple times during the major Plinian Laacher See Eruption (12,900 BP). Dams formed both upstream and downstream of the broad tectonic Lower Neuwied Basin (LNB) which interrupts the narrow Rhine canyon. Here we document upstream damming of the Rhine River at the entrance to the LNB close to the present city of Koblenz due to overloading with tephra fall into the Rhine and its major tributaries, the Moselle and the Lahn. The dam was formed repeatedly during rapid pumiceous tephra fall events and breached during breaks in eruptive activity, causing extensive, high-energy flooding throughout the entire basin. The ephemeral Koblenz dams differed significantly from “normal” volcanically-induced dams by consisting principally of washed-together pumice clasts and some driftwood. The porous nature of pumice and its ability to absorb water were crucial factors. Thus, a large volume percentage of the tephra that had fallen into the Rhine floated submerged within the upper part of the water column or swam at the surface. Moreover, the absorption of the river water by the pumice clasts increased the sediment:water ratio of the two-phase flow considerably. We here present a model of dam formation resembling the formation of ice jams. We visualize the Koblenz dams to have been elongate, partly floating and partly grounded, permeable plugs many kilometers long and rising no higher than the flood plain. Damming was most plausibly initiated in the LNB within the area of maximum tephra loading and propagated upstream in a chain reaction comparable to the formation of traffic jams. A major dam was finally accumulated at the bottleneck entrance to the LNB, a site combining several favorable conditions: the upstream multi-channel Rhine was confined to a single channel, change of flow direction by 125°, extremely low gradient (0.19‰) starting already 24 km upstream of the bottleneck, constant decrease of flow velocity over many kilometers towards the bottleneck and the Moselle River - largest tributary of the Rhine within the LNB and an important conveyor of additional tephra masses – entered the Rhine only 700 m upstream of the bottleneck. We assume that the Koblenz dams could only have formed and been stabilized by an extremely long “foot region” that extended many kilometers downstream and that was possibly connected to one or several low-rise secondary jams/dams. The backwater of Lake Brohl that was dammed by pyroclastic flows 7 km downstream of the LNB about halfway through the eruption extended further and further upstream into the LNB during the second Plinian stage of the Laacher See Eruption and was probably a major factor contributing to the formation and large size of Koblenz Dam No.4. The Koblenz dams were probably not completely sealed most of the time. This way the major pre-eruptive Rhine channel received some water. An equilibrium condition was established that enabled the dams to remain stable as long as tephra fell into the Rhine relatively continuously.
Nicolas A Margot - One of the best experts on this subject based on the ideXlab platform.
-
rare emergence of drug resistance in hiv 1 treatment naive patients receiving elvitegravir cobicistat emtricitabine tenofovir alafenamide for 144 weeks
Journal of Clinical Virology, 2018Co-Authors: Nicolas A Margot, Scott Mccallister, Michael D Miller, Christian CallebautAbstract:Abstract Background The single tablet regimen (STR) composed of elvitegravir (E), cobicistat (C), emtricitabine (F), and tenofovir alafenamide (TAF) (E/C/F/TAF) was compared to the STR composed of E, C, F, and tenofovir disoproxil fumarate (TDF) (E/C/F/TDF) in 2 phase 3 studies in 1733 HIV-1 infected treatment-naive adults. Superior efficacy of E/C/F/TAF compared to E/C/F/TDF was demonstrated at Week 144 with 84% treatment success compared to 80%, respectively, along with significantly better outcomes of bone and renal safety. Objectives Analyze the emergence of HIV-1 resistance in treatment-naive adults receiving E/C/F/TAF for 144 weeks. Study design We conducted an integrated resistance analysis of the 2 Phase 3 studies, comprising pretreatment HIV-1 sequencing for all participants (N = 1733) and post-baseline HIV-1 resistance analysis for participants with virologic failure (HIV-1 RNA ≥400 copies/mL). Results Primary resistance-associated mutations (Rams) were observed pre-treatment in 7.4% (NRTI-Rams), 18.1% (NNRTI-Rams), and 3.3% (PI-Rams) of enrolled subjects. Baseline HIV-1 subtype or pre-existing Rams did not affect E/C/F/TAF treatment response at week 144. Virologic failure resistance analyses were conducted for 28/866 (3.2%) and 30/867 (3.5%) patients in the E/C/F/TAF and E/C/F/TDF arms, respectively. Over the 3-year study, the rate of resistance emergence remained low at 1.4% in each group (12/866 in E/C/F/TAF; 12/867 in E/C/F/TDF). Resistant virus emerged in 24 patients who developed resistance to antiretrovirals in the regimens (E/C/F/TAF: M184V/I [1.3%], INSTI-Rams [0.9%], K65R/N [0.2%]; E/C/F/TDF: M184V/I [1.0%], INSTI-Rams [0.9%], K65R/N [0.5%]). Conclusions Resistance emergence was rare (1.4%) with similar patterns of emergent mutations in both groups. M184V/I was the most prevalent RAM (1.2% overall).
-
infrequent development of drug resistance in hiv 1 infected treatment naive subjects after 96 weeks of treatment with elvitegravir cobicistat emtricitabine tenofovir alafenamide or elvitegravir cobicistat emtricitabine tenofovir disoproxil fumarate
Antiviral Therapy, 2017Co-Authors: Nicolas A Margot, Scott Mccallister, Michael D Miller, Stephanie Cox, Moupali Das, Christian CallebautAbstract:BACKGROUND Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide reverse transcriptase inhibitor tenofovir (TFV) that loads lymphocytes with TFV-diphosphate more efficiently than tenofovir disoproxil fumarate (TDF). The single-tablet regimen (STR) comprising elvitegravir, cobicistat, emtricitabine and TAF (E/C/F/TAF) has demonstrated non-inferiority to the STR of E/C/F/TDF in clinical studies, with high proportions of subjects achieving HIV-1 RNA <50 copies/ml at week 48 that were maintained through week 96. A resistance analysis of the combined Phase III clinical studies through 96 weeks is described here. METHODS Genotypic and phenotypic susceptibility to antiretrovirals (ARVs) was evaluated for subjects with HIV-1 RNA ≥400 copies/ml at time of virological failure (VF) or early discontinuation. RESULTS Through week 96, VF resistance analyses were conducted for 24 subjects in each arm (2.8%, 24/866 and 2.8%, 24/867; for E/C/F/TAF and E/C/F/TDF arms, respectively). Primary resistance development to ARVs of the regimen occurred in 10 of 24 subjects in the E/C/F/TAF arm, and 8 of 24 subjects in the E/C/F/TDF arm (E/C/F/TAF: M184V/I, n=9; integrase strand-transfer inhibitor resistance-associated mutations [INSTI-Rams], n=8; K65R/N, n=2; E/C/F/TDF: M184V/I, n=6; INSTI-Rams, n=5; K65R/N, n=3). The emergent resistance mutations were similar between the treatment arms. CONCLUSIONS E/C/F/TAF achieved a high level of virological suppression in HIV-1 treatment-naive subjects through 96 weeks of treatment, with infrequent resistance development and comparable genotypic changes across both the E/C/F/TAF and E/C/F/TDF treatment groups.
Cornelia Park - One of the best experts on this subject based on the ideXlab platform.
-
boundary conditions for damming of a large river by fallout during the 12 900 bp plinian laacher see eruption germany syn eruptive rhine damming ii
Journal of Volcanology and Geothermal Research, 2020Co-Authors: Cornelia Park, Hansulrich SchminckeAbstract:Abstract The Rhine River (Germany) - the largest river in Western Europe - was dammed by pyroclastic material multiple times during the major Plinian Laacher See Eruption (12,900 BP). Dams formed both upstream and downstream of the broad tectonic Lower Neuwied Basin (LNB) which interrupts the narrow Rhine canyon. Here we document upstream damming of the Rhine River at the entrance to the LNB close to the present city of Koblenz due to overloading with tephra fall into the Rhine and its major tributaries, the Moselle and the Lahn. The dam was formed repeatedly during rapid pumiceous tephra fall events and breached during breaks in eruptive activity, causing extensive, high-energy flooding throughout the entire basin. The ephemeral Koblenz dams differed significantly from “normal” volcanically-induced dams by consisting principally of washed-together pumice clasts and some driftwood. The porous nature of pumice and its ability to absorb water were crucial factors. Thus, a large volume percentage of the tephra that had fallen into the Rhine floated submerged within the upper part of the water column or swam at the surface. Moreover, the absorption of the river water by the pumice clasts increased the sediment:water ratio of the two-phase flow considerably. We here present a model of dam formation resembling the formation of ice jams. We visualize the Koblenz dams to have been elongate, partly floating and partly grounded, permeable plugs many kilometers long and rising no higher than the flood plain. Damming was most plausibly initiated in the LNB within the area of maximum tephra loading and propagated upstream in a chain reaction comparable to the formation of traffic jams. A major dam was finally accumulated at the bottleneck entrance to the LNB, a site combining several favorable conditions: the upstream multi-channel Rhine was confined to a single channel, change of flow direction by 125°, extremely low gradient (0.19‰) starting already 24 km upstream of the bottleneck, constant decrease of flow velocity over many kilometers towards the bottleneck and the Moselle River - largest tributary of the Rhine within the LNB and an important conveyor of additional tephra masses – entered the Rhine only 700 m upstream of the bottleneck. We assume that the Koblenz dams could only have formed and been stabilized by an extremely long “foot region” that extended many kilometers downstream and that was possibly connected to one or several low-rise secondary jams/dams. The backwater of Lake Brohl that was dammed by pyroclastic flows 7 km downstream of the LNB about halfway through the eruption extended further and further upstream into the LNB during the second Plinian stage of the Laacher See Eruption and was probably a major factor contributing to the formation and large size of Koblenz Dam No.4. The Koblenz dams were probably not completely sealed most of the time. This way the major pre-eruptive Rhine channel received some water. An equilibrium condition was established that enabled the dams to remain stable as long as tephra fell into the Rhine relatively continuously.
Scott Mccallister - One of the best experts on this subject based on the ideXlab platform.
-
rare emergence of drug resistance in hiv 1 treatment naive patients receiving elvitegravir cobicistat emtricitabine tenofovir alafenamide for 144 weeks
Journal of Clinical Virology, 2018Co-Authors: Nicolas A Margot, Scott Mccallister, Michael D Miller, Christian CallebautAbstract:Abstract Background The single tablet regimen (STR) composed of elvitegravir (E), cobicistat (C), emtricitabine (F), and tenofovir alafenamide (TAF) (E/C/F/TAF) was compared to the STR composed of E, C, F, and tenofovir disoproxil fumarate (TDF) (E/C/F/TDF) in 2 phase 3 studies in 1733 HIV-1 infected treatment-naive adults. Superior efficacy of E/C/F/TAF compared to E/C/F/TDF was demonstrated at Week 144 with 84% treatment success compared to 80%, respectively, along with significantly better outcomes of bone and renal safety. Objectives Analyze the emergence of HIV-1 resistance in treatment-naive adults receiving E/C/F/TAF for 144 weeks. Study design We conducted an integrated resistance analysis of the 2 Phase 3 studies, comprising pretreatment HIV-1 sequencing for all participants (N = 1733) and post-baseline HIV-1 resistance analysis for participants with virologic failure (HIV-1 RNA ≥400 copies/mL). Results Primary resistance-associated mutations (Rams) were observed pre-treatment in 7.4% (NRTI-Rams), 18.1% (NNRTI-Rams), and 3.3% (PI-Rams) of enrolled subjects. Baseline HIV-1 subtype or pre-existing Rams did not affect E/C/F/TAF treatment response at week 144. Virologic failure resistance analyses were conducted for 28/866 (3.2%) and 30/867 (3.5%) patients in the E/C/F/TAF and E/C/F/TDF arms, respectively. Over the 3-year study, the rate of resistance emergence remained low at 1.4% in each group (12/866 in E/C/F/TAF; 12/867 in E/C/F/TDF). Resistant virus emerged in 24 patients who developed resistance to antiretrovirals in the regimens (E/C/F/TAF: M184V/I [1.3%], INSTI-Rams [0.9%], K65R/N [0.2%]; E/C/F/TDF: M184V/I [1.0%], INSTI-Rams [0.9%], K65R/N [0.5%]). Conclusions Resistance emergence was rare (1.4%) with similar patterns of emergent mutations in both groups. M184V/I was the most prevalent RAM (1.2% overall).
-
infrequent development of drug resistance in hiv 1 infected treatment naive subjects after 96 weeks of treatment with elvitegravir cobicistat emtricitabine tenofovir alafenamide or elvitegravir cobicistat emtricitabine tenofovir disoproxil fumarate
Antiviral Therapy, 2017Co-Authors: Nicolas A Margot, Scott Mccallister, Michael D Miller, Stephanie Cox, Moupali Das, Christian CallebautAbstract:BACKGROUND Tenofovir alafenamide (TAF) is a novel prodrug of the nucleotide reverse transcriptase inhibitor tenofovir (TFV) that loads lymphocytes with TFV-diphosphate more efficiently than tenofovir disoproxil fumarate (TDF). The single-tablet regimen (STR) comprising elvitegravir, cobicistat, emtricitabine and TAF (E/C/F/TAF) has demonstrated non-inferiority to the STR of E/C/F/TDF in clinical studies, with high proportions of subjects achieving HIV-1 RNA <50 copies/ml at week 48 that were maintained through week 96. A resistance analysis of the combined Phase III clinical studies through 96 weeks is described here. METHODS Genotypic and phenotypic susceptibility to antiretrovirals (ARVs) was evaluated for subjects with HIV-1 RNA ≥400 copies/ml at time of virological failure (VF) or early discontinuation. RESULTS Through week 96, VF resistance analyses were conducted for 24 subjects in each arm (2.8%, 24/866 and 2.8%, 24/867; for E/C/F/TAF and E/C/F/TDF arms, respectively). Primary resistance development to ARVs of the regimen occurred in 10 of 24 subjects in the E/C/F/TAF arm, and 8 of 24 subjects in the E/C/F/TDF arm (E/C/F/TAF: M184V/I, n=9; integrase strand-transfer inhibitor resistance-associated mutations [INSTI-Rams], n=8; K65R/N, n=2; E/C/F/TDF: M184V/I, n=6; INSTI-Rams, n=5; K65R/N, n=3). The emergent resistance mutations were similar between the treatment arms. CONCLUSIONS E/C/F/TAF achieved a high level of virological suppression in HIV-1 treatment-naive subjects through 96 weeks of treatment, with infrequent resistance development and comparable genotypic changes across both the E/C/F/TAF and E/C/F/TDF treatment groups.
