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Gilles Peytavin - One of the best experts on this subject based on the ideXlab platform.
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Placental transfer of Elvitegravir and cobicistat in an Ex Vivo human cotyledon double perfusion model
AIDS, 2018Co-Authors: Valentine Faure Bardon, Dominique Duro, Chloé Dussaux, Minh Patrick Le, Laurent Mandelbrot, Gilles PeytavinAbstract:To determine the transplacental pharmacokinetics of the HIV integrase strand transfer inhibitor Elvitegravir and of cobicistat, a cytochrome P450 inhibitor used as a pharmacoenhancer in antiretroviral therapy. Maternal-to-fetal transfer across the term human placenta was investigated with the ex-vivo dually perfused cotyledon model, in seven open-circuit experiments and 10 closed-circuit (recirculating) experiments. Elvitegravir and cobicistat were added to a maternal perfusate containing 2 g/l of human serum albumin and antipyrine, as a marker to validate the cotyledon's viability. Elvitegravir and cobicistat concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. For Elvitegravir, in open-circuit experiments the mean (±SD) fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 30 to 90 min) was 19 ± 13% and the mean clearance index was 0.46 ± 0.21; in the closed-circuit model, after 3 h of perfusion the FTR was 20 ± 10% and the mean accumulation index was 12.28 ± 5.57. For cobicistat, in the open perfusions the FTR was 23 ± 13% and the mean clearance index was 0.63 ± 0.34; in the closed perfusions after 3 h the fetal-to-maternal ratio of cobicistat was 21 ± 11%. The mean accumulation index was 3.46 ± 2.19 CONCLUSION:: The two models concurred to show moderate placental transfer of Elvitegravir and cobicistat across the placenta as well as Elvitegravir accumulation in the placenta tissue. Whether this may lead to toxicities and modifications in fetal or placental metabolism requires clinical studies.
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placental transfer of Elvitegravir and cobicistat in an ex vivo human cotyledon double perfusion model
AIDS, 2017Co-Authors: Valentine Faurebardon, Dominique Duro, Chloé Dussaux, Laurent Mandelbrot, Gilles PeytavinAbstract:OBJECTIVE To determine the transplacental pharmacokinetics of the HIV integrase strand transfer inhibitor Elvitegravir and of cobicistat, a cytochrome P450 inhibitor used as a pharmacoenhancer in antiretroviral therapy. DESIGN AND METHODS Maternal-to-fetal transfer across the term human placenta was investigated with the ex-vivo dually perfused cotyledon model, in seven open-circuit experiments and 10 closed-circuit (recirculating) experiments. Elvitegravir and cobicistat were added to a maternal perfusate containing 2 g/l of human serum albumin and antipyrine, as a marker to validate the cotyledon's viability. Elvitegravir and cobicistat concentrations were measured using ultraperformance liquid chromatography coupled with tandem mass spectrometry. RESULTS For Elvitegravir, in open-circuit experiments the mean (±SD) fetal transfer rate (FTR) (fetal/maternal concentration at steady state from 30 to 90 min) was 19 ± 13% and the mean clearance index was 0.46 ± 0.21; in the closed-circuit model, after 3 h of perfusion the FTR was 20 ± 10% and the mean accumulation index was 12.28 ± 5.57. For cobicistat, in the open perfusions the FTR was 23 ± 13% and the mean clearance index was 0.63 ± 0.34; in the closed perfusions after 3 h the fetal-to-maternal ratio of cobicistat was 21 ± 11%. The mean accumulation index was 3.46 ± 2.19 CONCLUSION:: The two models concurred to show moderate placental transfer of Elvitegravir and cobicistat across the placenta as well as Elvitegravir accumulation in the placenta tissue. Whether this may lead to toxicities and modifications in fetal or placental metabolism requires clinical studies.
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switch as maintenance to Elvitegravir cobicistat emtricitabine tenofovir disoproxil fumarate week 48 results in a clinical cohort
Journal of Antimicrobial Chemotherapy, 2017Co-Authors: Marine Perrier, Gilles Peytavin, Charlotte Charpentier, Minh Le, Louis Blondel, Benoit Visseaux, Veronique JolyAbstract:To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate as a single-tablet regimen (STR) using the PCR signal of the plasma viral load (pVL) assay and determination of plasma drug concentration ( C 24 ).This was an observational single-centre study enrolling antiretroviral-treated patients with pVL 45 ng/mL, the protein-adjusted IC 95 .In this clinical cohort of virologically suppressed patients switching to STR, most subjects had adequate Elvitegravir C 24 values with a high proportion maintaining virological suppression with no residual viraemia until W48.
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switch as maintenance to Elvitegravir cobicistat emtricitabine tenofovir disoproxil fumarate week 48 results in a clinical cohort
Journal of Antimicrobial Chemotherapy, 2017Co-Authors: Marine Perrier, Gilles Peytavin, Charlotte Charpentier, Louis Blondel, Benoit Visseaux, Veronique Joly, Adriana Pinto, Sophie MatheronAbstract:Objectives To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate as a single-tablet regimen (STR) using the PCR signal of the plasma viral load (pVL) assay and determination of plasma drug concentration ( C 24 ). Patients and methods This was an observational single-centre study enrolling antiretroviral-treated patients with pVL 45 ng/mL, the protein-adjusted IC 95 . Conclusions In this clinical cohort of virologically suppressed patients switching to STR, most subjects had adequate Elvitegravir C 24 values with a high proportion maintaining virological suppression with no residual viraemia until W48.
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Switch as maintenance to Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate: week 48 results in a clinical cohort.
The Journal of antimicrobial chemotherapy, 2017Co-Authors: Marine Perrier, Gilles Peytavin, Charlotte Charpentier, Louis Blondel, Benoit Visseaux, Veronique Joly, Adriana Pinto, Sophie Matheron, Yazdan YazdanpanahAbstract:Objectives To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate as a single-tablet regimen (STR) using the PCR signal of the plasma viral load (pVL) assay and determination of plasma drug concentration ( C 24 ). Patients and methods This was an observational single-centre study enrolling antiretroviral-treated patients with pVL 45 ng/mL, the protein-adjusted IC 95 . Conclusions In this clinical cohort of virologically suppressed patients switching to STR, most subjects had adequate Elvitegravir C 24 values with a high proportion maintaining virological suppression with no residual viraemia until W48.
Veronique Joly - One of the best experts on this subject based on the ideXlab platform.
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switch as maintenance to Elvitegravir cobicistat emtricitabine tenofovir disoproxil fumarate week 48 results in a clinical cohort
Journal of Antimicrobial Chemotherapy, 2017Co-Authors: Marine Perrier, Gilles Peytavin, Charlotte Charpentier, Minh Le, Louis Blondel, Benoit Visseaux, Veronique JolyAbstract:To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate as a single-tablet regimen (STR) using the PCR signal of the plasma viral load (pVL) assay and determination of plasma drug concentration ( C 24 ).This was an observational single-centre study enrolling antiretroviral-treated patients with pVL 45 ng/mL, the protein-adjusted IC 95 .In this clinical cohort of virologically suppressed patients switching to STR, most subjects had adequate Elvitegravir C 24 values with a high proportion maintaining virological suppression with no residual viraemia until W48.
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switch as maintenance to Elvitegravir cobicistat emtricitabine tenofovir disoproxil fumarate week 48 results in a clinical cohort
Journal of Antimicrobial Chemotherapy, 2017Co-Authors: Marine Perrier, Gilles Peytavin, Charlotte Charpentier, Louis Blondel, Benoit Visseaux, Veronique Joly, Adriana Pinto, Sophie MatheronAbstract:Objectives To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate as a single-tablet regimen (STR) using the PCR signal of the plasma viral load (pVL) assay and determination of plasma drug concentration ( C 24 ). Patients and methods This was an observational single-centre study enrolling antiretroviral-treated patients with pVL 45 ng/mL, the protein-adjusted IC 95 . Conclusions In this clinical cohort of virologically suppressed patients switching to STR, most subjects had adequate Elvitegravir C 24 values with a high proportion maintaining virological suppression with no residual viraemia until W48.
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Switch as maintenance to Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate: week 48 results in a clinical cohort.
The Journal of antimicrobial chemotherapy, 2017Co-Authors: Marine Perrier, Gilles Peytavin, Charlotte Charpentier, Louis Blondel, Benoit Visseaux, Veronique Joly, Adriana Pinto, Sophie Matheron, Yazdan YazdanpanahAbstract:Objectives To assess, in a clinical cohort, the efficacy of switching current ART in virologically suppressed patients to Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate as a single-tablet regimen (STR) using the PCR signal of the plasma viral load (pVL) assay and determination of plasma drug concentration ( C 24 ). Patients and methods This was an observational single-centre study enrolling antiretroviral-treated patients with pVL 45 ng/mL, the protein-adjusted IC 95 . Conclusions In this clinical cohort of virologically suppressed patients switching to STR, most subjects had adequate Elvitegravir C 24 values with a high proportion maintaining virological suppression with no residual viraemia until W48.
Josep M Llibre - One of the best experts on this subject based on the ideXlab platform.
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discontinuation of dolutegravir Elvitegravir cobicistat and raltegravir because of toxicity in a prospective cohort
Hiv Medicine, 2019Co-Authors: Josep M Llibre, Alexandra Montoliu, F Homar, Mario Riera, Juan Tiraboschi, Juan Ambrosioni, Adrian Curran, Josep Maria Miro, Pere Domingo, N AbdulghaniAbstract:Objectives The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. Methods A population-based, prospective, multicentre cohort study was carried out. Treatment-naive subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA Results A total of 4165 subjects (37% treatment-naive) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or Elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus Elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal. Conclusions In this large prospective cohort study, patients receiving dolutegravir, raltegravir or Elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for Elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.
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overdose of Elvitegravir cobicistat emtricitabine tenofovir alafenamide in an hiv 1 infected subject with attempted suicide
Infection, 2019Co-Authors: Hortensia Alvarez, Nieves Valcarce, Jesus Garciagonzalez, Helena Diazcambre, Ana. Marino, Josep M LlibreAbstract:Introduction Data are lacking regarding overdose of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF).
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Discontinuation of dolutegravir, Elvitegravir/cobicistat and raltegravir because of toxicity in a prospective cohort.
HIV medicine, 2019Co-Authors: Josep M Llibre, Alexandra Montoliu, F Homar, Mario Riera, Juan Tiraboschi, Juan Ambrosioni, Adrian Curran, Pere Domingo, N AbdulghaniAbstract:Objectives The aim of the study was to assess the rates of discontinuation of integrase inhibitor regimens because of any neuropsychiatric adverse event (NPAE) and the factors associated with discontinuation. Methods A population-based, prospective, multicentre cohort study was carried out. Treatment-naive subjects starting therapy with a regimen containing integrase inhibitors, or those switching to such a regimen, with plasma HIV-1 RNA Results A total of 4165 subjects (37% treatment-naive) started regimens containing dolutegravir (n = 1650; 91% with abacavir), raltegravir (n = 930) or Elvitegravir/cobicistat (n = 1585). There were no significant differences among regimens in the rate of discontinuation because of any AE. Rates of discontinuation because of NPAEs were low but higher for dolutegravir/abacavir/lamivudine [2.1%; 2.9 (95% confidence interval (CI) 2.0, 4.2) discontinuations/100 patients/year] versus Elvitegravir/cobicistat (0.5%; 0.8 (95% CI 0.3, 1.5) discontinuations/100 patients/year], with significant differences among centres for dolutegravir/abacavir/lamivudine and NPAEs (P = 0.003). We identified an association of female gender and lower CD4 count with increased risk of discontinuation because of any AE [Incidence ratio (IR) 2.3 (95% CI 1.4, 4.0) and 1.8 (95% CI 1.1, 2.8), respectively]. Female gender, age > 60 years and abacavir use were not associated with NPAE discontinuations. NPAEs were commonly grade 1-2, and had been present before and improved after drug withdrawal. Conclusions In this large prospective cohort study, patients receiving dolutegravir, raltegravir or Elvitegravir/cobicistat did not show significant differences in the rate of discontinuation because of any toxicity. The rate of discontinuations because of NPAEs was low, but was significantly higher for dolutegravir than for Elvitegravir/cobicistat, with significant differences among centres, suggesting that greater predisposition to believe that a given adverse event is caused by a given drug of some treating physicians might play a role in the discordance seen between cohorts.
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Overdose of Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in an HIV-1-infected subject with attempted suicide
Infection, 2018Co-Authors: Hortensia Alvarez, Nieves Valcarce, Helena Díaz-cambre, Jesús García-gonzález, Ana. Marino, Josep M LlibreAbstract:Introduction Data are lacking regarding overdose of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF).
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Correction: An Indirect Comparison of Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate and Abacavir/Lamivudine + Dolutegravir in Initial Therapy
PLOS ONE, 2016Co-Authors: Josep M Llibre, David Piontkowsky, Georg M N Behrens, Stephane Bouee, Geraldine Reilly, Peter Borg, Francois Raffi, Graeme Moyle, Felipe RogattoAbstract:Objectives The objective of this analysis is to perform an indirect comparison of Elvitegravir, cobicistat, emtricitabine and tenofovir DF (E/C/F/TDF) to abacavir/lamivudine and dolutegravir (ABC/3TC + DTG) by using 2 trials evaluating each of these regimens in comparison to efavirenz, emtricitabine and tenofovir DF (EFV/FTC/TDF).
Pierre Gantner - One of the best experts on this subject based on the ideXlab platform.
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Elvitegravir-Cobicistat-Emtricitabine-Tenofovir Alafenamide Single-tablet Regimen for Human Immunodeficiency Virus Postexposure Prophylaxis
Clinical Infectious Diseases, 2020Co-Authors: Pierre Gantner, Mohamed Faouzi Souala, Nadia Valin, F Ajana, Laurent Cotte, Elisabeth Bouvet, Mojgan Hessamfar, Anne Simon, E Rouveix, F. Bani-sadrAbstract:We evaluated an Elvitegravir–cobicistat–emtricitabine–tenofovir alafenamide single-tablet regimen for human immunodeficiency virus postexposure prophylaxis. The completion rate and adherence were good, and the tolerance was acceptable; no seroconversion was observed. We confirm that this regimen could be appropriate for postexposure prophylaxis.
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Elvitegravir cobicistat emtricitabine tenofovir alafenamide single tablet regimen for human immunodeficiency virus postexposure prophylaxis
Clinical Infectious Diseases, 2019Co-Authors: Pierre Gantner, Mohamed Faouzi Souala, Nadia Valin, F Ajana, Laurent Cotte, Elisabeth Bouvet, Mojgan Hessamfar, Anne Simon, E Rouveix, F BanisadrAbstract:We evaluated an Elvitegravir-cobicistat-emtricitabine-tenofovir alafenamide single-tablet regimen for human immunodeficiency virus postexposure prophylaxis. The completion rate and adherence were good, and the tolerance was acceptable; no seroconversion was observed. We confirm that this regimen could be appropriate for postexposure prophylaxis. CLINICAL TRIALS REGISTRATION: NCT02998320.
David Piontkowsky - One of the best experts on this subject based on the ideXlab platform.
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bone mineral density in virologically suppressed people aged 60 years or older with hiv 1 switching from a regimen containing tenofovir disoproxil fumarate to an Elvitegravir cobicistat emtricitabine and tenofovir alafenamide single tablet regimen a
The Lancet HIV, 2019Co-Authors: Franco Maggiolo, David Piontkowsky, Maria Gracia Mateogarcia, Yongwu Shao, Ian Mcnicholl, Federico Pulido, Francois Raffi, Giuliano Rizzardini, Jean Michel Molina, Richard HaubrichAbstract:Summary Background Tenofovir alafenamide is associated with less renal and bone toxicity than tenofovir disoproxil fumarate and might improve the long-term safety of antiretroviral therapy. We aimed to investigate the effect on bone mineral density of switching from a regimen containing tenofovir disoproxil fumarate to one containing tenofovir alafenamide in participants aged 60 years and older. Methods We did a prospective, open-label, multicentre, randomised trial in 36 European centres. Participants were virologically suppressed (HIV-1 RNA ClinicalTrials.gov , NCT02616783 . Findings Between Dec 22, 2015, and March 21, 2018, 167 participants were randomly assigned to Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide (n=111 [66%]) or tenofovir disoproxil fumarate (n=56 [34%]). One participant in the Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide group did not receive treatment and was excluded from all analyses. At week 48, the mean percentage change in spine bone mineral density was 2·24% (SD 3·27) in the Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide group and −0·10% (3·39) in the tenofovir disoproxil fumarate group (between-group difference 2·43% [95% CI 1·34–3·52]; p Interpretation The significantly improved bone mineral density, overall safety, and efficacy data show the feasibility of switching from a regimen containing tenofovir disoproxil fumarate to Elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV aged 60 years or older. Funding Gilead Sciences.
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Correction: An Indirect Comparison of Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate and Abacavir/Lamivudine + Dolutegravir in Initial Therapy
PLOS ONE, 2016Co-Authors: Josep M Llibre, David Piontkowsky, Georg M N Behrens, Stephane Bouee, Geraldine Reilly, Peter Borg, Francois Raffi, Graeme Moyle, Felipe RogattoAbstract:Objectives The objective of this analysis is to perform an indirect comparison of Elvitegravir, cobicistat, emtricitabine and tenofovir DF (E/C/F/TDF) to abacavir/lamivudine and dolutegravir (ABC/3TC + DTG) by using 2 trials evaluating each of these regimens in comparison to efavirenz, emtricitabine and tenofovir DF (EFV/FTC/TDF).
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correction an indirect comparison of efficacy and safety of Elvitegravir cobicistat emtricitabine tenofovir disoproxil fumarate and abacavir lamivudine dolutegravir in initial therapy
PLOS ONE, 2016Co-Authors: Josep M Llibre, David Piontkowsky, Georg M N Behrens, Stephane Bouee, Geraldine Reilly, Peter Borg, Francois Raffi, Graeme Moyle, Felipe RogattoAbstract:Objectives The objective of this analysis is to perform an indirect comparison of Elvitegravir, cobicistat, emtricitabine and tenofovir DF (E/C/F/TDF) to abacavir/lamivudine and dolutegravir (ABC/3TC + DTG) by using 2 trials evaluating each of these regimens in comparison to efavirenz, emtricitabine and tenofovir DF (EFV/FTC/TDF).
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An Indirect Comparison of Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate and Abacavir/Lamivudine + Dolutegravir in Initial Therapy.
PloS one, 2016Co-Authors: Josep M Llibre, David Piontkowsky, Georg M N Behrens, Stephane Bouee, Geraldine Reilly, Peter Borg, Francois Raffi, Graeme Moyle, Felipe RogattoAbstract:Objectives The objective of this analysis is to perform an indirect comparison of Elvitegravir, cobicistat, emtricitabine and tenofovir DF (E/C/F/TDF) to abacavir/lamivudine and dolutegravir (ABC/3TC + DTG) by using 2 trials evaluating each of these regimens in comparison to efavirenz, emtricitabine and tenofovir DF (EFV/FTC/TDF).
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Drug Interactions with Cobicistat- or Ritonavir-Boosted Elvitegravir.
AIDS reviews, 2016Co-Authors: Thai Nguyen, Ian Mcnicholl, Joseph M Custodio, Javier Szwarcberg, David PiontkowskyAbstract:Cobicistat and ritonavir are structurally distinct compounds that both potently inhibit cytochrome P450 (CYP) 3A, the metabolizing enzyme primarily responsible for the elimination of several antiretroviral medications, and, as such, are pharmacokinetic boosters for antiretroviral agents that require longer dosing intervals. Recently, cobicistat was approved for the treatment of HIV-1 infection in treatment-naive adults as a component of a single-tablet regimen consisting of cobicistat-boosted Elvitegravir plus emtricitabine and tenofovir disoproxil fumarate. While studies have demonstrated that boosting with either cobicistat or ritonavir results in comparable plasma exposure of the target antiretroviral agent, a better understanding of drug-drug interactions between cobicistat- and ritonavir-boosted antiretrovirals and other medications will inform treatment decisions in HIV-infected patients. In connection with their distinct structural properties, COBI and RTV differ with respect to their drug-drug interaction profiles. Compared with ritonavir, cobicistat lacks induction potential and is a more specific inhibitor of 3A and therefore, has reduced effects on other CYP isoforms. To date, more studies have assessed ritonavir drug-drug interactions with other medications than have assessed cobicistat drug-drug interactions. The objective of this article is to review the drug-drug interactions when cobicistat- or ritonavir-boosted Elvitegravir, cobicistat, or Elvitegravir/cobicistat/emtricitabine/tenofovir are coadministered with antiretroviral therapies or drugs that are either substrates, inducers, or inhibitors of the CYP3A metabolic pathway, as well as with drugs that alter intra-gastric pH or are substrates of P-gp, in order to inform the proper use of Elvitegravir/cobicistat/emtricitabine/tenofovir.