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https://www.readbyqxmd.com/read/27912079/a-humanized-mouse-model-for-hiv-2-infection-and-efficacy-testing-of-a-single-pill-triple-drug-combination-anti-retroviral-therapy
#1
Shuang Hu, Charles Preston Neff, Dipu Mohan Kumar, Yuichiro Habu, Sarah R Akkina, Takahiro Seki, Ramesh Akkina
While HIV-2 is a causative agent for AIDS in addition to the better studied HIV-1, there is currently no suitable animal model for experimental studies for HIV-2 infection and evaluating promising drugs in vivo. Here we evaluated humanized mice for their susceptibility to HIV-2 infection and tested a single-pill three drug formulation of anti-retrovirals (NRTIs abacavir and lamivudine, integrase inhibitor dolutegravir) (trade name, Triumeq(R)). Our results showed that hu-mice are susceptible to HIV-2 infection showing persistent viremia and CD4 T cell loss, key hallmarks of AIDS pathogenesis...
November 29, 2016: Virology
https://www.readbyqxmd.com/read/27904105/evaluation-of-the-lipid-concentrations-after-switching-from-antiretroviral-drug-tenofovir-disoproxil-fumarate-emtricitabine-to-abacavir-sulfate-lamivudine-in-virologically-suppressed-human-immunodeficiency-virus-infected-patients
#2
Hirotaka Arae, Masao Tateyama, Hideta Nakamura, Daisuke Tasato, Kaoru Kami, Kyoko Miyagi, Saori Maeda, Hitoshi Uehara, Makiko Moromi, Katsunori Nakamura, Jiro Fujita
Objective Recently, tenofovir disoproxil fumatate (TDF)-related side effects, such as renal nephrotoxicity and reduction of bone mineral density, have been reported. Consequently, increased switching from fixed-dose tablet TDF and emtricitabine (TDF/FTC) to abacavir and lamivudine (ABC/3TC) has occurred. Interestingly, while TDF has a lipid-lowering property, one of the ABC-related side effects is hyperlipidemia. Therefore, such switching could cause lipid elevation. To evaluate the change in lipid levels associated with switching from TDF/FTC to ABC/3TC in virologically-suppressed human immunodeficiency virus (HIV)-infected patients...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27889293/stability-behaviour-of-antiretroviral-drugs-and-their-combinations-5-characterization-of-novel-degradation-products-of-abacavir-sulfate-by-mass-and-nuclear-magnetic-resonance-spectrometry
#3
Moolchand Kurmi, Archana Sahu, Saranjit Singh
In the present study, degradation behaviour of abacavir sulfate was evaluated in solution and solid stress conditions. Solution state studies resulted in formation of eleven degradation products; of which two were also formed on solid stress. The same were separated by high performance liquid chromatography. They were characterized using liquid chromatography-high resolution mass spectrometry, liquid chromatography-multistage mass spectrometry and hydrogen/deuterium exchange mass spectrometry data. Additionally, seven degradation products were isolated and subjected to 1D and 2D nuclear magnetic resonance studies for their structural confirmation...
November 5, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27860104/higher-rates-of-neuropsychiatric-adverse-events-leading-to-dolutegravir-discontinuation-in-women-and-older-patients
#4
C Hoffmann, T Welz, M Sabranski, M Kolb, E Wolf, H-J Stellbrink, C Wyen
OBJECTIVES: Dolutegravir (DTG), a second-generation integrase strand transfer inhibitor (INSTI), is now among the most frequently used antiretroviral agents. However, recent reports have raised concerns about potential neurotoxicity. METHODS: We performed a retrospective analysis of a cohort of HIV-infected patients who had initiated an INSTI in two large German out-patient clinics between 2007 and 2016. We compared discontinuation rates because of adverse events (AEs) within 2 years of starting treatment with dolutegravir, raltegravir or elvitegravir/cobicistat...
January 2017: HIV Medicine
https://www.readbyqxmd.com/read/27846791/clinical-experience-with-dolutegravir-abacavir-lamivudine-in-hiv-hcv-co-infected-patients-treated-with-a-sofosbuvir-based-regimen-safety-and-efficacy
#5
Tamara M Johnson, Raymund Sison, James P Fallon, Prerak P Shukla, Sristi Bhattarai, Herbert Galang, Richard Habeeb, Jihad Slim
BACKGROUND: There is no known reason to suspect an adverse drug interaction between dolutegravir-based antiretroviral therapy and sofosbuvir, simeprevir, or ledipasvir. There is a paucity of clinical data for this combination. METHODS: Prospective, open-label study of patients with HIV well controlled on dolutegravir, abacavir, and lamivudine, who were co-infected with HCV genotype 1, and required therapy with simeprevir plus sofosbuvir or sofosbuvir/ledipasvir single-tablet regimen (STR) for 12 weeks...
November 2016: HIV Clinical Trials
https://www.readbyqxmd.com/read/27824625/intolerance-of-dolutegravir-containing-combination-antiretroviral-therapy-regimens-in-real-life-clinical-practice
#6
Mark G J de Boer, Guido E L van den Berk, Natasja van Holten, Josephine E Oryszcyn, Willemien Dorama, Daoud Ait Moha, Kees Brinkman
OBJECTIVE: Dolutegravir (DGV) is one of the preferred antiretroviral agents in first-line combination antiretroviral therapy (cART). Though considered to be a well tolerated drug, we aimed to determine the actual rate, timing and detailed motivation of stopping DGV in a real-life clinical setting. DESIGN: A cohort study including all patients who started DGV in two HIV treatment centers in The Netherlands. METHODS: All cART-naïve and cART-experienced patients who had started DGV were identified from the institutional HIV databases...
November 28, 2016: AIDS
https://www.readbyqxmd.com/read/27815125/meeting-report-29th-international-conference-on-antiviral-research-in-la-jolla-ca-usa
#7
REVIEW
R Anthony Vere Hodge
The 29th International Conference on Antiviral Research (ICAR) was held in La Jolla, CA, USA from April 17 to 21, 2016. This report opens with a tribute to the late Chris McGuigan, a Past-President of ISAR, then continues with summaries of the principal invited lectures. Doug Richman (Elion Award) investigated HIV resistance, Bob Vince (Holý Award) showed how carbocyclic nucleoside analogs led to abacavir and Jerome Deval (Prusoff Award) explained how his group chose to seek a nucleoside analog to treat RSV...
November 1, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27804313/antiretroviral-treatment-for-hiv-infection-swedish-recommendations-2016
#8
Jaran Eriksen, Jan Albert, Anders Blaxhult, Christina Carlander, Leo Flamholc, Magnus Gisslén, Filip Josephson, Olof Karlström, Lars Navér, Veronica Svedhem, Aylin Yilmaz, Anders Sönnerborg
The Swedish Medical Products Agency and the Swedish Reference Group for Antiviral Therapy (RAV) have jointly published recommendations for the treatment of HIV infection on seven previous occasions (2002, 2003, 2005, 2007, 2009, 2011 and 2014). In February 2016, an expert group under the guidance of RAV once more revised the guidelines. The most important updates in the present guidelines are as follows: Tenofovir alafenamide (TAF) has recently been registered. TAF has several advantages over tenofovir disoproxilfumarate (TDF) and is recommended instead of TDF in most cases...
November 2, 2016: Infectious Diseases
https://www.readbyqxmd.com/read/27801778/antiviral-screening-of-multiple-compounds-against-ebola-virus
#9
Stuart D Dowall, Kevin Bewley, Robert J Watson, Seshadri S Vasan, Chandradhish Ghosh, Mohini M Konai, Gro Gausdal, James B Lorens, Jason Long, Wendy Barclay, Isabel Garcia-Dorival, Julian Hiscox, Andrew Bosworth, Irene Taylor, Linda Easterbrook, James Pitman, Sian Summers, Jenny Chan-Pensley, Simon Funnell, Julia Vipond, Sue Charlton, Jayanta Haldar, Roger Hewson, Miles W Carroll
In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests...
October 27, 2016: Viruses
https://www.readbyqxmd.com/read/27798221/optimization-of-the-strength-of-the-efavirenz-lamivudine-abacavir-fixed-dose-combination-for-paediatric-patients
#10
Naïm Bouazza, Tim R Cressey, Frantz Foissac, Andrzej Bienczak, Paolo Denti, Helen McIlleron, David Burger, Martina Penazzato, Marc Lallemant, Edmund V Capparelli, Jean-Marc Treluyer, Saïk Urien
BACKGROUND: Child-friendly, low-cost, solid, oral fixed-dose combinations (FDCs) of efavirenz with lamivudine and abacavir are urgently needed to improve clinical management and drug adherence for children. METHODS: Data were pooled from several clinical trials and therapeutic drug monitoring datasets from different countries. The number of children/observations was 505/3667 for efavirenz. Population pharmacokinetic analyses were performed using a non-linear mixed-effects approach...
October 24, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27781100/how-can-we-achieve-universal-access-to-low-cost-treatment-for-hiv
#11
EDITORIAL
Andrew M Hill, Anton L Pozniak
Mass production of low-cost antiretrovirals (ARVs) has already allowed over 17 million individuals to access treatment for HIV infection, mainly in low-income countries. It is possible to manufacture combination ARVs for $110 per person-year, using tenofovir (TDF), lamivudine (3TC) and efavirenz (EFV). New combinations of ARVs costing as little as $60 per person-year will be available in the near future. Pre-exposure prophylaxis using TDF in combination with either 3TC or emtricitabine (FTC) could also be provided for less than $90 per person-year...
October 5, 2016: Journal of Virus Eradication
https://www.readbyqxmd.com/read/27780535/etravirine-inhibits-abcg2-drug-transporter-and-affects-transplacental-passage-of-tenofovir-disoproxil-fumarate
#12
Josef Reznicek, Martina Ceckova, Lenka Tupova, Frantisek Staud
INTRODUCTION: All HIV positive pregnant women should receive combination antiretroviral therapy (cART) to prevent mother-to-child transmission (MTCT) of the virus. It has recently been shown that fetal exposure of nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and abacavir is decreased by placental ABC transporters p-glycoprotein (ABCB1) and BCRP (ABCG2). The aim of this study was to evaluate transporter-mediated drug-drug interactions (DDI) between etravirine (TMC125), a novel non-nucleoside reverse transcriptase inhibitor used in cART, and the NRTIs and to assess the relevance of such DDI for transplacental pharmacokinetics of TDF and abacavir...
November 2016: Placenta
https://www.readbyqxmd.com/read/27750332/-how-to-individualize-drug-therapy-based-on-pharmacogenetic-information-a-systematic-review-of-published-guidelines
#13
Susanne Hafner, Sabine Haubensak, Tanusree Paul, Oliver Zolk
Background | Differences (polymorphisms) in genes encoding drug targets, drug transport proteins, or drug metabolizing enzymes may be responsible, among other factors, for the observed variation in patients' responses to medications. The field of pharmacogenetics aims to identify patients at higher genetically-determined risk of adverse effects or poor response to medication. This information would allow for modification of dosage or substitution with alternative therapy. However, there is a lack of awareness of pharmacogenetic clinical practise guidelines...
October 2016: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/27749561/long-term-effectiveness-of-unboosted-atazanavir-plus-abacavir-lamivudine-in-subjects-with-virological-suppression-a-prospective-cohort-study
#14
Josep M Llibre, Alessandro Cozzi-Lepri, Court Pedersen, Matti Ristola, Marcelo Losso, Amanda Mocroft, Viktar Mitsura, Karolin Falconer, Fernando Maltez, Marek Beniowski, Vincenzo Vullo, Gamal Hassoun, Elena Kuzovatova, János Szlavik, Anastasiia Kuznetsova, Hans-Jürgen Stellbrink, Claudine Duvivier, Simon Edwards, Kamilla Laut, Roger Paredes
Effectiveness data of an unboosted atazanavir (ATV) with abacavir/lamivudine (ABC/3TC) switch strategy in clinical routine are scant.We evaluated treatment outcomes of ATV + ABC/3TC in pretreated subjects in the EuroSIDA cohort when started with undetectable plasma HIV-1 viral load (pVL), performing a time to loss of virological response (TLOVR <50 copies/mL) and a snapshot analysis at 48, 96, and 144 weeks. Virological failure (VF) was defined as confirmed pVL >50 copies/mL.We included 285 subjects, 67% male, with median baseline CD4 530 cells, and 44 months with pVL ≤50 copies/mL...
October 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27743681/-abacavir-lamivudine-unboosted-atazanavir-in-routine-clinical-practice-twelve-years-experience
#15
M Eulalia Valencia, Luz Martín-Carbonero, Victoria Moreno, José Ignacio Bernardino, M Luisa Montes, Rocío Montejano
OBJECTIVE: To describe the experience using the combination abacavir, lamivudine plus non-boosted atazanavir (ABC/3TC+ATV) in a group of pretreated patients. PATIENTS AND METHODS: We performed a retrospective observational study to describe baseline characteristics and the evolution of patients who had received or were treating with ABC/3TC+ATV, from November 2004 and June 15th 2015, in the clinical setting. RESULTS: Overall, 236 patients were included in the study...
October 13, 2016: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/27736859/dolutegravir-plus-two-nucleoside-reverse-transcriptase-inhibitors-versus-efavirenz-plus-two-nucleoside-reverse-transcriptase-inhibitors-as-initial-antiretroviral-therapy-for-people-with-hiv-a-systematic-review
#16
George W Rutherford, Hacsi Horvath
BACKGROUND: Dolutegravir (DTG) is a once-daily unboosted second-generation integrase-inhibitor that along with two nucleoside reverse transcriptase inhibitors is one of several regimens recommended by the United States, United Kingdom and European Union for first-line antiretroviral treatment of people with HIV infection. Our objective was to review the evidence for the efficacy and safety of DTG-based first-line regimens compared to efavirenz (EFV)-based regimens. METHODS: We conducted a systematic review...
2016: PloS One
https://www.readbyqxmd.com/read/27733708/integrase-strand-transfer-inhibitor-associated-diabetes-mellitus-a-case-report
#17
Peter S Fong, Devon M Flynn, Christopher D Evans, P Todd Korthuis
Integrase strand transfer inhibitors (INSTIs) have become integral antiretroviral therapy (ART) agents for treating HIV infection. We report the case of a 44-year-old male with a history of hemophilia A who developed diabetes mellitus four months after switching from abacavir, lamivudine, and efavirenz to abacavir, lamivudine, and raltegravir. Hemoglobin A1C normalized without further need for exogenous insulin after raltegravir was switched back to efavirenz. In this case report, we will review a possible mechanism for INSTI-induced hyperglycemia and/or diabetes mellitus...
October 12, 2016: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/27727331/abacavir-lamivudine-plus-rilpivirine-is-an-effective-and-safe-strategy-for-hiv-1-suppressed-patients-48-week-results-of-the-simriki-retrospective-study
#18
Jesús Troya, Pablo Ryan, Esteban Ribera, Daniel Podzamczer, Victor Hontañón, Jose Alberto Terrón, Vicente Boix, Santiago Moreno, Pilar Barrufet, Manuel Castaño, Ana Carrero, María José Galindo, Ignacio Suárez-Lozano, Hernando Knobel, Miguel Raffo, Javier Solís, María Yllescas, Herminia Esteban, Juan González-García, Juan Berenguer, Arkaitz Imaz
OBJECTIVES: Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected patients. METHODS: We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments. The primary objective was HIV-1 RNA <50 copies/mL at week 48...
2016: PloS One
https://www.readbyqxmd.com/read/27720019/pharmacogenomics-and-adverse-drug-reactions-primetime-and-not-ready-for-primetime-tests
#19
David A Khan
Adverse drug reactions (ADRs) are a relatively common cause of morbidity and mortality. Many factors can contribute to ADRs, including genetics. The degree to which genetics contributes to ADRs is not entirely clear and varies by drug, as well as the type of ADR. Pharmacogenetics and, more recently, pharmacogenomics have been applied to the field of ADRs for both predictable ADRs and hypersensitivity drug reactions. Evaluations for glucose-6-phosphate dehydrogenase and thiopurine S-methyltransferase are commonplace clinical tests to reduce hematologic problems associated with drugs, such as dapsone and azathioprine, respectively...
October 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27716093/effectiveness-and-safety-of-generic-version-of-abacavir-lamivudine-and-efavirenz-in-treatment-na%C3%A3-ve-hiv-infected-patients-a-nonrandomized-open-label-phase-iv-study-in-cali-colombia-2011-2012
#20
Jaime Galindo, Pedro Amariles, Héctor F Mueses-Marín, Jaime A Hincapié, Sebastián González-Avendaño, Ximena Galindo-Orrego
BACKGROUND: Generic drug policies are often associated with concerns about the quality and effectiveness of these products. Phase IV clinical trials may be a suitable design to assess the effectiveness and safety of generic drugs. The objective of this study was to describe the effectiveness and the safety of the generic abacavir/lamivudine and efavirenz in treatment-naïve HIV-infected patients. METHODS: A monocentric, nonrandomized, open-label, phase IV study in treatment naïve HIV-infected patients 18 years or older with indication to receive abacavir/lamivudine and efavirenz were recruited from a program that provides comprehensive outpatient consultation and continuing care...
October 3, 2016: BMC Infectious Diseases
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