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elvitegravir

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https://www.readbyqxmd.com/read/29318459/incidence-and-predictors-of-single-drug-discontinuation-according-to-the-presence-of-hcv-coinfection-in-hiv-patients-from-the-icona-foundation-cohort-study
#1
Sebastiano Leone, Milensu Shanyinde, Alessandro Cozzi Lepri, Fiona C Lampe, Pietro Caramello, Andrea Costantini, Andrea Giacometti, Andrea De Luca, Antonella Cingolani, Francesca Ceccherini Silberstein, Massimo Puoti, Andrea Gori, Antonella d'Arminio Monforte
To evaluate incidence rates of and predictors for any antiretroviral (ART) drug discontinuation by HCV infection status in a large Italian cohort of HIV infected patients. All patients enrolled in ICONA who started combination antiretroviral therapy (cART) containing abacavir or tenofovir or emtricitabine or lamivudine plus efavirenz or rilpivirine or atazanavir/r or darunavir/r (DRV/r) or lopinavir/r or dolutegravir or elvitegravir or raltegravir were included. Multivariate Poisson regression models were used to determine factors independently associated with single ART drug discontinuation...
January 9, 2018: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/29239896/ex-vivo-antiretroviral-potency-of-newer-integrase-strand-transfer-inhibitors-cabotegravir-and-bictegravir-in-hiv-1-non-b-subtypes
#2
Ujjwal Neogi, Kamlendra Singh, Shambhu G Aralaguppe, Leonard C Rogers, Duncan T Njenda, Stefan G Sarafianos, Bo Hejdeman, Anders Sönnerborg
OBJECTIVE: To determine the antiretroviral activity of the integrase strand transfer inhibitors (INSTIs), raltegravir, elvitegravir, dolutegravir, cabotegravir and bictegravir, against different subtypes as well as primary and acquired drug resistance mutations (DRM) in a patient-cohort infected with diverse subtypes. DESIGN: Biochemical and virological drug sensitivity analysis using patient derived HIV-1 genes and cross-sectional/longitudinal clinical study. METHODS: Assays for inhibition of 3'-end processing (IC50-3P), strand transfer (IC50-ST) and drug sensitivity (DSA) for five INSTIs were done using patient-derived integrase or gag-pol genes from subtypes A1, B, C, 01_AE and 02_AG...
December 12, 2017: AIDS
https://www.readbyqxmd.com/read/29239232/effectiveness-of-single-and-multiple-tablet-antiretroviral-regimens-in-correctional-setting-for-treatment-experienced-hiv-patients
#3
Andrew Merker, Melissa Badowski, Thomas Chiampas, Sarah E Pérez, Mahesh Patel, Jeremy Young, Ryan Werner
Minimal information is available regarding antiretroviral prescribing patterns and outcomes for HIV patients in correctional systems. This study analyzes single- (STR) and multiple- (MTR) tablet regimen effectiveness in patients receiving HIV telemedicine care through the Illinois Department of Corrections (IDOC). This study involves a retrospective review of HIV-positive adult patients in IDOC on either an STR (efavirenz, rilpivirine, elvitegravir based) or an MTR (emtricitabine/tenofovir with atazanavir/ritonavir, darunavir/ritonavir, or raltegravir)...
January 1, 2017: Journal of Correctional Health Care
https://www.readbyqxmd.com/read/29225131/role-of-tenofovir-alafenamide-taf-in-the-treatment-and-prophylaxis-of-hiv-and-hbv-infections
#4
REVIEW
Erik De Clercq
Tenofovir (TFV) is the cornerstone of the treatment and prophylaxis of HIV infections. It has been routinely used in its prodrug form TDF (tenofovir disoproxil fumarate) combined with emtricitabine ((-)FTC) and other antiretroviral agents. TDF has now been replaced by TAF (tenofovir alafenamide) which allows better uptake by the lymphoid tissue. In combination with elvitegravir (E), cobicistat (C), emtricitabine (F), TAF can be advocated as an STR (single tablet regimen, Genvoya®) for the treatment of HIV infections...
December 7, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29214223/novel-elvitegravir-nanoformulation-approach-to-suppress-the-viral-load-in-hiv-infected-macrophages
#5
Yuqing Gong, Pallabita Chowdhury, Narasimha M Midde, Mohammad A Rahman, Murali M Yallapu, Santosh Kumar
Purpose: Monocytes serve as sanctuary sites for HIV-1 from which virus is difficult to be eliminated. Therefore, an effective viral suppression in monocytes is critical for effective antiretroviral therapy (ART). This study focuses on a new strategy using nanoformulation to optimize the efficacy of ART drugs in HIV-infected monocytes. Methods: Poly(lactic-co-glycolic acid) (PLGA)-based elvitegravir nanoparticles (PLGA-EVG) were prepared by nano-precipitation technique...
December 2017: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/29210830/tenofovir-associated-nephrotoxicity-among-a-us-national-historical-cohort-of-hiv-infected-veterans-risk-modification-by-concomitant-antiretrovirals
#6
Joanne LaFleur, Adam P Bress, Stephen Esker, Kristin Knippenberg, Jacob Crook, Heather Nyman, Roger Bedimo, Pablo Tebas, Lisa Rosenblatt
BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been associated with renal complications. The third agent in TDF-containing antiretroviral regimens may modify that risk. We compared renal adverse outcomes among treatment-naïve HIV-infected patients initiating TDF-containing regimens including efavirenz (EFV) or other agents. SETTING: This population-based historical cohort study used national Veterans Health Administration (VHA) clinical and administrative datasets to identify treatment-naïve HIV-infected veterans initiating antiretroviral therapy (ART) with TDF/emtricitabine (FTC)+EFV, rilpivirine (RPV), elvitegravir/cobicistat (EVG/c), or ritonavir (RTV)-boosted protease inhibitors (PIs) from 2003-2015...
November 27, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29199485/a-safety-evaluation-of-raltegravir-for-the-treatment-of-hiv
#7
Rosa de Miguel, Rocio Montejano, Natalia Stella-Ascariz, Jose R Arribas
Raltegravir (RAL) was the first commercialized agent from a new drug class with an innovative target, the integrase. Since its introduction in clinical practice RAL has become widely used for the treatment of HIV-1 infected patients. A decade after its approval, this article reviews key evidence from RAL with a special interest on safety outcomes. Areas covered: Pharmacologic, safety and efficacy data of RAL from clinical trials and post-commercialization published reports are hereby summarized after a literature review including PubMed search, relating proceedings and abstracts from relevant international HIV conferences, assessment reports from European and United States regulatory agencies and treatment guidelines (World Health Organization, United States Department of Health and Human Services and European AIDS Clinical Society), up to October 2017...
December 5, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29194118/trends-in-art-prescription-durability-and-modification-new-drugs-more-changes-but-less-failure
#8
Ellen F Eaton, Ashutosh Tamhane, Thibaut Davy-Mendez, W Christopher Mathews, Richard D Moore, Michael S Saag, Michael J Mugavero
OBJECTIVE: To evaluate the real world durability of contemporary ART for treatment naïve people living with HIV (PLWH). DESIGN: A retrospective follow up study in a multisite cohort METHODS:: This study of the CNICS (CFAR Network of Integrated Clinical Systems) cohort integrates data from 8 Center for AIDS Research (CFARs). PLWH initiating ART between 2007-2014 were included. Durability was defined as time from the initiation until discontinuation/modification using Kaplan-Meier survival curves...
November 30, 2017: AIDS
https://www.readbyqxmd.com/read/29173177/integrase-strand-transfer-inhibitors-and-the-emergence-of-immune-reconstitution-inflammatory-syndrome-iris
#9
Mina Psichogiou, Dimitrios Basoulis, Maria Tsikala-Vafea, Stefanos Vlachos, Christos J Kapelios, Georgios L Daikos
BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a major concern when starting highly active anti-retroviral therapy (HAART) in new patients and especially late presenters. This study attempts to identify risk factors for IRIS and investigate whether certain treatment regimens increase the probability of IRIS for patients at risk. METHODS: Retrospective single-centre study of HIV patients treated with HAART. RESULTS: A total of 417 patients were included...
November 22, 2017: Current HIV Research
https://www.readbyqxmd.com/read/29145807/durability-of-switch-regimens-based-on-rilpivirine-or-on-integrase-inhibitors-both-in-association-with-tenofovir-and-emtricitabine-in-hiv-infected-virologically-suppressed-patients
#10
Nicola Gianotti, Andrea Poli, Silvia Nozza, Laura Galli, Nadia Galizzi, Marco Ripa, Marco Merli, Alessia Carbone, Vincenzo Spagnuolo, Adriano Lazzarin, Antonella Castagna
BACKGROUND: Switch strategies based on rilpivirine/tenofovir/emtricitabine or on an integrase inhibitor (InSTI) plus tenofovir/emtricitabine have never been compared in randomized clinical trials. The main aim of the study was to investigate the durability of these two switch regimens in virologically suppressed, HIV-infected patients. METHODS: Retrospective analysis of patients who started rilpivirine or an InSTI (both with tenofovir and emtricitabine) with <50 HIV-RNA copies/mL and had at least one HIV-RNA assessed while receiving the study regimen...
November 16, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/29112064/placental-transfer-of-elvitegravir-and-cobicistat-in-an-ex-vivo-human-cotyledon-double-perfusion-model
#11
Valentine Faure Bardon, Laurent Mandelbrot, Dominique Duro, Chloé Dussaux, Minh Le, Gilles Peytavin
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 7 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...
November 2, 2017: AIDS
https://www.readbyqxmd.com/read/29105160/strength-in-amalgamation-newer-combination-agents-for-hiv-and-implications-for-practice
#12
Christopher McCoy, Melissa Badowski, Elizabeth Sherman, Rustin Crutchley, Ethan Smith, Daniel B Chastain
Antiretroviral (ART) therapy for treatment of human immunodeficiency virus (HIV) infection has undergone significant changes over the past 30 years. Many single tablet regimens (STR), including newer fixed dose combination (FDC) tablets, are available, offering patients several options for choosing a treatment regimen that works best for them. Given these changes, patients are more likely to adhere to treatment, achieve better clinical outcomes, and experience both fewer side effects and drug-drug interactions...
November 3, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/29096670/hiv-treatment-simplification-to-elvitegravir-cobicistat-emtricitabine-tenofovir-disproxil-fumarate-e-c-f-tdf-plus-darunavir-a-pharmacokinetic-study
#13
Marianne Harris, Bruce Ganase, Birgit Watson, P Richard Harrigan, Julio S G Montaner, Mark W Hull
BACKGROUND: As a simplification strategy for treatment-experienced HIV-infected patients who have achieved virologic suppression on a multi-drug, multi-class antiretroviral regimen, the aim of this study was to evaluate the safety, efficacy, and pharmacokinetics of once-daily elvitegravir/cobicistat/emtricitabine/tenofovir disproxil fumarate (E/C/F/TDF) with darunavir. METHODS: A single arm, open-label 48-week study was conducted of regimen simplification to E/C/F/TDF plus darunavir 800 mg daily from stable therapy including two nucleoside/nucleotide reverse transcriptase inhibitors, a ritonavir-boosted protease inhibitor, and an integrase inhibitor...
November 2, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/29091217/tenofovir-disoproxil-fumarate-emtricitabine-plus-ritonavir-boosted-lopinavir-or-cobicistat-boosted-elvitegravir-as-a-single-tablet-regimen-for-hiv-post-exposure-prophylaxis
#14
A Inciarte, L Leal, E González, A León, C Lucero, J Mallolas, B Torres, M Laguno, J Rojas, M Martínez-Rebollar, A González-Cordón, A Cruceta, J A Arnaiz, J M Gatell, F García
Objectives: To assess HIV-1 post-exposure prophylaxis (PEP) non-completion at day 28, comparing ritonavir-boosted lopinavir versus cobicistat-boosted elvitegravir as a single-tablet regimen (STR), using tenofovir disoproxil fumarate/emtricitabine with both of these therapies. Methods: A prospective, open, randomized clinical trial was performed. Individuals attending the emergency room due to potential sexual exposure to HIV and who met criteria for PEP were randomized 1:3 into two groups receiving either 400/100 mg of lopinavir/ritonavir (n = 38) or 150/150 mg of elvitegravir/cobicistat (n = 119), with both groups also receiving 245/200 mg of tenofovir disoproxil fumarate/emtricitabine...
October 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29070877/probing-resistance-mutations-in-retroviral-integrases-by-direct-measurement-of-dolutegravir-fluorescence
#15
Eloïse Thierry, Samuel Lebourgeois, Françoise Simon, Olivier Delelis, Eric Deprez
FDA-approved integrase strand transfer inhibitors (raltegravir, elvitegravir and dolutegravir) efficiently inhibit HIV-1 replication. Here, we present fluorescence properties of these inhibitors. Dolutegravir displays an excitation mode particularly dependent on Mg(2+) chelation, allowing to directly probe its Mg(2+)-dependent binding to the prototype foamy virus (PFV) integrase. Dolutegravir-binding studied by both its fluorescence anisotropy and subsequent emission enhancement, strictly requires a preformed integrase/DNA complex, the ten terminal base pairs from the 3'-end of the DNA reactive strand being crucial to optimize dolutegravir-binding in the context of the ternary complex...
October 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28968669/human-immunodeficiency-virus-type-1-drug-resistance-mutations-update
#16
Robert W Shafer
As treatment options coalesce around a smaller number of antiretroviral drugs (ARVs), data are emerging on the drug resistance mutations (DRMs) selected by the most widely used ARVs and on the impact of these DRMs on ARV susceptibility and virological response to first- and later-line treatment regimens. Recent studies have described the DRMs that emerge in patients receiving tenofovir prodrugs, the nonnucleoside reverse transcriptase inhibitors efavirenz and rilpivirine, ritonavir-boosted lopinavir, and the integrase inhibitors raltegravir and elvitegravir...
September 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28961682/effect-of-cobicistat-on-tenofovir-disoproxil-fumarate-tdf-what-is-true-for-taf-may-also-be-true-for-tdf
#17
Dario Cattaneo, Davide Minisci, Sara Baldelli, Cristina Mazzali, Andrea Giacomelli, Laura Milazzo, Paola Meraviglia, Chiara Resnati, Giuliano Rizzardini, Emilio Clementi, Massimo Galli, Cristina Gervasoni
BACKGROUND: The dose of tenofovir alafenamide (TAF) is reduced from 25 to 10 mg daily when given with boosting agents. However, such dose reduction has never been adopted for tenofovir disoproxil fumarate (TDF). In this study we aim to quantify the effect of cobicistat both on tenofovir concentrations and TDF durability in real life setting. METHODS: HIV-positive patients receiving TDF-containing antiretroviral therapies with at least one assessment of tenofovir plasma trough concentrations were included in the study...
September 25, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28956664/investigational-hiv-integrase-inhibitors-in-phase-i-and-phase-ii-clinical-trials
#18
REVIEW
Yingshan Han, Thibault Mesplède, Mark A Wainberg
To date, three HIV integrase strand transfer inhibitors (INSTIs), i.e. raltegravir, elvitegravir and dolutegravir, have been approved for clinical use. Recent research has focused on new integrase inhibitors including those targeting non-catalytic sites of HIV integrase. Areas covered: This paper reviews two investigational INSTIs in phase I and II clinical trials, bictegravir (BIC) and cabotegravir (CAB), as well as an investigational noncatalytic integrase inhibitor (NCINI) termed BI 224436. Expert opinion: Data from phase I and II clinical trials demonstrate that CAB has good efficacy and is well-tolerated...
November 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28951475/mutations-located-outside-the-integrase-gene-can-confer-resistance-to-hiv-1-integrase-strand-transfer-inhibitors
#19
Isabelle Malet, Frédéric Subra, Charlotte Charpentier, Gilles Collin, Diane Descamps, Vincent Calvez, Anne-Geneviève Marcelin, Olivier Delelis
Resistance to the integrase strand transfer inhibitors raltegravir and elvitegravir is often due to well-identified mutations in the integrase gene. However, the situation is less clear for patients who fail dolutegravir treatment. Furthermore, most in vitro experiments to select resistance to dolutegravir have resulted in few mutations of the integrase gene. We performed an in vitro dolutegravir resistance selection experiment by using a breakthrough method. First, MT4 cells were infected with human immunodeficiency virus type 1 (HIV-1) Lai...
September 26, 2017: MBio
https://www.readbyqxmd.com/read/28945911/hdl-cholesterol-efflux-capacity-in-newly-diagnosed-hiv-and-effects-of-antiretroviral-therapy
#20
Mabel Toribio, Min Hi Park, Markella V Zanni, Gregory K Robbins, Tricia H Burdo, Kenneth C Williams, Meghan N Feldpausch, Lauren Stone, Kathleen Melbourne, Steven K Grinspoon, Michael L Fitzgerald
Context: In the general population, high-density lipoprotein (HDL) cholesterol efflux capacity (HCEC) relates inversely to incident cardiovascular events. Previous studies have suggested that HCEC is decreased in HIV and that antiretroviral therapy (ART) initiation might improve HCEC. Objective: To evaluate HCEC in the context of ART initiation and immune activation in HIV. Design and Outcome Measures: Baseline HCEC from 10 ART-naive HIV-infected males and 12 prospectively matched non-HIV-infected males were analyzed...
November 1, 2017: Journal of Clinical Endocrinology and Metabolism
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