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https://www.readbyqxmd.com/read/28494325/hiv-1-integrase-inhibitor-resistance-among-treatment-na%C3%A3-ve-patients-in-the-west-of-scotland
#1
A Bradley-Stewart, C Urcia, A MacLean, C Aitken, R Gunson
BACKGROUND: Transmitted integrase inhibitor resistance is rare, with only a small number of cases reported world-wide to date. OBJECTIVES: The aim of this study was to assess whether transmitted integrase inhibitor resistance has occurred in Scotland and if so, could there be a case for performing genotypic integrase resistance testing at baseline. STUDY DESIGN: The study population consisted of 106 treatment naïve, newly diagnosed, HIV positive patients...
April 23, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28472323/hiv-1-strains-belonging-to-large-phylogenetic-clusters-show-accelerated-escape-from-integrase-inhibitors-in-cell-culture-compared-with-viral-isolates-from-singleton-small-clusters
#2
Bluma G Brenner, Ruxandra-Ilinca Ibanescu, Maureen Oliveira, Michel Roger, Isabelle Hardy, Jean-Pierre Routy, Fred Kyeyune, Miguel E Quiñones-Mateu, Mark A Wainberg
Objectives: Viral phylogenetics revealed two patterns of HIV-1 spread among MSM in Quebec. While most HIV-1 strains ( n  =   2011) were associated with singleton/small clusters (cluster size 1-4), 30 viral lineages formed large networks (cluster size 20-140), contributing to 42% of diagnoses between 2011 and 2015. Herein, tissue culture selections ascertained if large cluster lineages possessed higher replicative fitness than singleton/small cluster isolates, allowing for viral escape from integrase inhibitors...
May 2, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28449051/viral-kinetics-in-semen-with-different-antiretroviral-families-in-treatment-na%C3%A3-ve-hiv-infected-patients-a-randomized-trial
#3
Alicia Gutierrez-Valencia, Omar J Benmarzouk-Hidalgo, Inmaculada Rivas-Jeremías, Nuria Espinosa, María Trujillo-Rodríguez, Tamara Fernandez-Magdaleno, Pompeyo Viciana, Luis F López-Cortés
Background: There are several regimens for starting antiretroviral treatment, but it remains unknown whether either of them is more advantageous regarding the time course and magnitude of HIV-RNA decay in semen. Objective: To evaluate the differential effect of different antiretroviral drug families on viral kinetics in seminal plasma of treatment-naïve HIV-infected patients. Methods: Phase II, randomized, open-label study in which participants were randomized 1:1:1 to receive tenofovir-DF plus emtricitabine, and either cobicistat-boosted elvitegravir (EVGcobi), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv)...
April 25, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28441177/right-hip-and-bilateral-shoulder-capsulitis-in-an-hiv-infected-individual-treated-with-elvitegravir-and-cobicistat
#4
Omar Al Tabaa, Victor Audren, Emma Hayton, Edouard Pertuiset, Laurent Blum
No abstract text is available yet for this article.
May 15, 2017: AIDS
https://www.readbyqxmd.com/read/28397245/interactions-between-integrase-inhibitors-and-human-arginase-1
#5
Lucia Lisi, Michela Pizzoferrato, Fabiola Teresa Miscioscia, Alessandra Topai, Pierluigi Navarra
The neuro-pathogenic mechanism(s) underlying HIV-associated neurocognitive disorders are mostly unknown. HIV-infected macrophages and microglial cells play a crucial role and the metabolic fate of l-arginine may be highly relevant to microglia activation. In this context, arginase (ARG), which uses l-arginine as substrate, can be on the same time a target and source of oxidative stress and inflammation. In this study, we investigated whether integrase strand transfer inhibitors share with the other antiretroviral drugs the ability to inhibit ARG activity...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28375875/emergent-drug-resistance-with-integrase-strand-transfer-inhibitor-based-regimens-incidence-and-risk-factors
#6
Katherine J Lepik, P Richard Harrigan, Benita Yip, Lu Wang, Marjorie A Robbins, Wendy W Zhang, Junine Toy, Linda Akagi, Viviane Dias Lima, Silvia Guillemi, Julio S G Montaner, Rolando Barrios
OBJECTIVES: To estimate the incidence of and risk factors for emergent resistance to integrase inhibitors (INSTI) and nucleoside(-tide) reverse transcriptase inhibitors (NRTI) in HIV-1-infected adults receiving an INSTI plus two NRTIs. DESIGN: Retrospective cohort study. METHODS: Persons ≥19 years were included if they received their first prescription for raltegravir, elvitegravir or dolutegravir in British Columbia, Canada in 2012-2014, and were followed to 31-Dec-2015...
April 3, 2017: AIDS
https://www.readbyqxmd.com/read/28356041/recent-advances-in-antiretroviral-agents-potent-integrase-inhibitors
#7
Mina Psichogiou, Garyphalia Poulakou, Dimitrios Basoulis, Dimitrios Paraskevis, Antonios Markogiannakis, George L Daikos
Integrase strand transfer inhibitors (INSTIs) belong to a novel class of antiretroviral agents that have emerged as the new first-line treatments. Three such compounds are currently available, raltegravir, elvitegravir, dolutegravir and two more under development, bictegravir and cabotegravir. These compounds share the same mode of action but exhibit different pharmacokinetic/ pharmacodynamic properties, and drug-drug interactions. A series of studies in the past decade have established their efficacy compared to previous regimens, both in treatment-naïve and experienced patients...
March 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28351160/extensive-bruising-and-elevated-rivaroxaban-plasma-concentration-in-a-patient-receiving-cobicistat-boosted-elvitegravir
#8
Deborah Yoong, Mark Naccarato, Kevin Gough
No abstract text is available yet for this article.
March 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28348149/pharmacokinetics-and-placental-transfer-of-elvitegravir-and-dolutegravir-and-other-antiretrovirals-during-pregnancy
#9
Bassam H Rimawi, Erica Johnson, Augustine Rajakumar, Sijia Tao, Yong Jiang, Scott Gillespie, Raymond F Schinazi, Mark Mirochnick, Martina L Badell, Rana Chakraborty
The integrase inhibitors, elvitegravir (EVG) and dolutegravir (DTG), rapidly decrease plasma HIV-1 viral load, a key factor in the prevention of maternal-to-fetal transmission of HIV-1. No data have been reported on the concentration of these drugs in cord blood, maternal peripheral blood mononuclear cells (PBMC) concentrations or placental tissue in pregnant women. We present in vivo pharmacokinetic data on antiretrovirals (ARV) within maternal and cord blood, and within placentae from HIV-1-infected pregnant women...
March 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28333303/efficacy-of-elvitegravir-cobicistat-emtricitabine-tenofovir-disoproxil-fumarate-as-treatment-for-primary-or-recent-hiv-infection-authors-response
#10
Silvia Nozza, Andrea Poli, Marco Ripa, Laura Galli, Stefania Chiappetta, Vincenzo Spagnuolo, Cristina Rovelli, Adriano Lazzarin, Antonella Castagna, Giuseppe Tambussi
No abstract text is available yet for this article.
March 14, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333231/tolerability-of-integrase-inhibitors-in-a-real-life-setting
#11
Judit Peñafiel, Elisa de Lazzari, Mireia Padilla, Jhon Rojas, Ana Gonzalez-Cordon, Jose L Blanco, Jordi Blanch, Maria A Marcos, Montserrat Lonca, Maria Martinez-Rebollar, Montserrat Laguno, Amparo Tricas, Ana Rodriguez, Josep Mallolas, Jose M Gatell, Esteban Martinez
Background: Integrase inhibitors have shown better tolerability than other drugs in clinical trials, but some post-marketing data have suggested potential differences among them. Aims: We compared rates and reasons for discontinuation of raltegravir-, elvitegravir- and dolutegravir-based regimens in a large cohort of HIV-infected patients. Methods: Retrospective analysis of a prospectively followed cohort including all antiretroviral-naive and all virologically suppressed antiretroviral-experienced patients prescribed a first regimen containing raltegravir, elvitegravir or dolutegravir with at least one follow-up visit...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28282300/a-randomized-double-blind-comparison-of-tenofovir-alafenamide-taf-vs-tenofovir-disoproxil-fumarate-tdf-each-coformulated-with-elvitegravir-cobicistat-and-emtricitabine-e-c-f-for-initial-hiv-1-treatment-week-144-results
#12
José R Arribas, Melanie Thompson, Paul E Sax, Bernhard Haas, Cheryl McDonald, David A Wohl, Edwin DeJesus, Amanda E Clarke, Susan Guo, Hui Wang, Christian Callebaut, Andrew Plummer, Andrew Cheng, Moupali Das, Scott McCallister
In two double-blind Phase 3 trials, 1733 antiretroviral-naïve adults were randomized to tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF), each coformulated with elvitegravir/cobicistat/emtricitabine (E/C/F). At 144 weeks, TAF was superior to TDF in virologic efficacy, with 84.2% vs. 80.0% having HIV-1 RNA <50 copies/mL (difference 4.2%; 95%CI 0.6% to 7.8%). TAF had less impact than TDF on bone mineral density and renal biomarkers. No participants on TAF had renal-related discontinuations vs 12 on TDF (P<0...
March 9, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28231276/alterations-in-cellular-pharmacokinetics-and-pharmacodynamics-of-elvitegravir-in-response-to-ethanol-exposure-in-hiv-1-infected-monocytic-u1-cells
#13
Narasimha M Midde, Namita Sinha, Pradeep B Lukka, Bernd Meibohm, Santosh Kumar
Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours...
2017: PloS One
https://www.readbyqxmd.com/read/28219799/uplc-ms-ms-method-for-the-simultaneous-quantification-of-three-new-antiretroviral-drugs-dolutegravir-elvitegravir-and-rilpivirine-and-other-thirteen-antiretroviral-agents-plus-cobicistat-and-ritonavir-boosters-in-human-plasma
#14
Marco Simiele, Alessandra Ariaudo, Amedeo De Nicolò, Fabio Favata, Martina Ferrante, Chiara Carcieri, Stefano Bonora, Giovanni Di Perri, Antonio De Avolio
Rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) are the latest antiretroviral drugs approved for treatment of HIV infection. Currently, poor information is currently available concerning their pharmacokinetic and pharmacodynamic properties, thus making the use of therapeutic drug monitoring for these drugs not useful. This lack of information is partially due to the absence of an high-throughput method for their simultaneous quantification together with other antiretroviral drugs. In this work, we describe the development and validation of a new UPLC-MS/MS method to quantify these drugs, together with other fourteen antiretroviral agents, in human plasma...
May 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28212411/lack-of-impact-of-pre-existing-t97a-hiv-1-integrase-mutation-on-integrase-strand-transfer-inhibitor-resistance-and-treatment-outcome
#15
Michael E Abram, Renee R Ram, Nicolas A Margot, Tiffany L Barnes, Kirsten L White, Christian Callebaut, Michael D Miller
T97A is an HIV-1 integrase polymorphism associated with integrase strand transfer inhibitor (INSTI) resistance. Using pooled data from 16 clinical studies, we investigated the prevalence of T97A (pre-existing and emergent) and its impact on INSTI susceptibility and treatment response in INSTI-naive patients who enrolled on elvitegravir (EVG)- or raltegravir (RAL)-based regimens. Prior to INSTI-based therapy, primary INSTI resistance-associated mutations (RAMs) were absent and T97A pre-existed infrequently (1...
2017: PloS One
https://www.readbyqxmd.com/read/28186251/switch-as-maintenance-to-elvitegravir-cobicistat-emtricitabine-tenofovir-disoproxil-fumarate-week-48-results-in-a-clinical-cohort
#16
Marine Perrier, Charlotte Charpentier, Gilles Peytavin, Minh Lê, Louis Blondel, Benoit Visseaux, Véronique Joly, Adriana Pinto, Sophie Matheron, Yazdan Yazdanpanah, Diane Descamps, Roland Landman
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 <50 copies/mL initiating elvitegravir-based STR...
June 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28182625/viability-of-primary-osteoblasts-after-treatment-with-tenofovir-alafenamide-lack-of-cytotoxicity-at-clinically-relevant-drug-concentrations
#17
Christian Callebaut, Yang Liu, Darius Babusis, Adrian Ray, Michael Miller, Kathryn Kitrinos
Tenofovir alafenamide (TAF) is a phosphonoamidate prodrug of the nucleotide HIV reverse transcriptase inhibitor tenofovir (TFV). TAF is approved for the treatment of HIV-1 infection as part of the single-tablet regimen containing elvitegravir, cobicistat, emtricitabine, and TAF. When dosed once-daily, TAF results in approximately 90% lower levels of plasma TFV and a 4-fold increase in intracellular TFV-diphosphate (TFV-DP) in PBMCs compared with the TFV prodrug tenofovir disoproxil fumarate (TDF). Several antiretrovirals, including TDF, have been associated with bone mineral density decreases in patients; the effect of clinically relevant TAF concentrations on primary osteoblast viability was therefore assessed in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28166190/pharmacokinetics-of-crushed-elvitegravir-combination-tablet-given-with-or-without-enteral-nutrition
#18
Mieke Jongbloed-de Hoon, Angela Colbers, Kirsten Velthoven-Graafland, Marjolijn Duisenberg-van Essenberg, Martine Kruijssen, Evertine Abbink, Reinout van Crevel, David Burger
We investigated whether a fixed-dose combination tablet of elvitegravir, cobicistat, emtricitabine, and tenofovirDF (Stribild®), can be crushed and combined with enteral nutrition without influencing pharmacokinetics. This was an open-label, 3-period, single dose, randomized, cross-over, trial in 24 healthy volunteers. Subjects received Stribild whole tablet with breakfast (reference), crushed/suspended Stribild+breakfast, crushed/suspended Stribild+enteral nutrition. Crushed/suspended Stribild plus enteral nutrition was bio-equivalent (90% CI between 80-125%) with a whole Stribild tablet...
January 3, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28160503/comment-on-efficacy-of-elvitegravir-cobicistat-emtricitabine-tenofovir-disoproxil-fumarate-as-treatment-for-primary-or-recent-hiv-infection
#19
Juan Ambrosioni, María M Mosquera, José M Miró
No abstract text is available yet for this article.
February 4, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28151023/emtricitabine-tenofovir-alafenamide-for-the-treatment-of-hiv
#20
REVIEW
Katya C Corado, Eric S Daar
Tenofovir alafenamide is a new oral prodrug of tenofovir resulting in relatively low plasma levels and rapid uptake into peripheral blood mononuclear cells in its active form. The United States Food and Drug Administration has now approved this drug coformulated with elvitegravir/cobicistat/emtricitabine, rilpivirine/emtricitabine and emtricitabine. United States guidelines now list this formulation as one of the preferred components of a variety of antiretroviral regimens, and is included as an alternative in other international guidelines, with the notable exception of the World Health Organization, mostly due to limited availability...
March 2017: Expert Opinion on Pharmacotherapy
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