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https://www.readbyqxmd.com/read/28921647/pharmacogenomics-implementation-at-the-national-institutes-of-health-clinical-center
#1
Tristan M Sissung, Jon W McKeeby, Jharana Patel, Juan J Lertora, Parag Kumar, Willy A Flegel, Sharon D Adams, Ellen J Eckes, Frank Mickey, Teri M Plona, Stephanie D Mellot, Ryan N Baugher, Xiaolin Wu, Daniel R Soppet, Mary E Barcus, Vivekananda Datta, Kristen M Pike, Gary DiPatrizio, William D Figg, Barry R Goldspiel
The National Institutes of Health Clinical Center (NIH CC) is the largest hospital in the United States devoted entirely to clinical research, with a highly diverse spectrum of patients. Patient safety and clinical quality are major goals of the hospital, and therapy is often complicated by multiple cotherapies and comorbidities. To this end, we implemented a pharmacogenomics program in 2 phases. In the first phase, we implemented genotyping for HLA-A and HLA-B gene variations with clinical decision support (CDS) for abacavir, carbamazepine, and allopurinol...
October 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28903510/changes-in-liver-steatosis-after-switching-from-efavirenz-to-raltegravir-among-human-immunodeficiency-virus-infected-patients-with-nonalcoholic-fatty-liver-disease
#2
Juan Macías, María Mancebo, Dolores Merino, Francisco Téllez, M Luisa Montes-Ramírez, Federico Pulido, Antonio Rivero-Juárez, Miguel Raffo, Montserrat Pérez-Pérez, Nicolás Merchante, Manuel Cotarelo, Juan A Pineda
Background: Antiretroviral drugs with a lower potential to induce hepatic steatosis in human immunodeficiency virus (HIV) infection need to be identified. We compared the effect of switching efavirenz (EFV) to raltegravir (RAL) on hepatic steatosis among HIV-infected patients with nonalcoholic fatty liver disease (NAFLD) receiving EFV plus 2 nucleoside analogues. Methods: HIV-infected patients on EFV plus tenofovir/emtricitabine or abacavir/lamivudine with NAFLD were randomized 1:1 to switch from EFV to RAL (400 mg twice daily), maintaining nucleoside analogues unchanged, or to continue with EFV plus 2 nucleoside analogues...
September 15, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28901945/correction-dolutegravir-abacavir-lamivudine-versus-current-art-in-virally-suppressed-patients-striiving-a-48-week-randomized-non-inferiority-open-label-phase-iiib-study
#3
Benoît Trottier, Jordan E Lake, Ken Logue, Cynthia Brinson, Lizette Santiago, Clare Brennan, Justin A Koteff, Brian Wynne, Judy Hopking, Catherine Granier, Michael Aboud
No abstract text is available yet for this article.
September 13, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28901212/a-retrospective-clinical-audit-of-general-practices-in-australia-to-determine-the-motivation-for-switch-to-dolutegravir-abacavir-lamivudine-and-clinical-outcomes
#4
Pedro E Ferrer, Mark Bloch, Norman Roth, Robert Finlayson, David Baker, Ken Koh, David Orth, Rimgaile Urbaityte, Dannae Brown, Fraser Drummond
The most common reasons for switching HIV-1 therapy in patients with virologic suppression are treatment regimen simplification and resolving tolerability issues. Single-pill regimens that include an integrase inhibitor are recommended options. A retrospective clinical audit was performed to determine the motivations for switching to dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC) at high HIV-caseload general practice clinics in Australia. The most common reasons for switching from a prior suppressive therapy to DTG/ABC/3TC were simplification of regimen, resolving toxicity/intolerance and patient preference (73%, 13% and 12%, respectively)...
January 1, 2017: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/28895059/central-nervous-system-penetrating-antiretrovirals-impair-energetic-reserve-in-striatal-nerve-terminals
#5
Kelly L Stauch, Katy Emanuel, Benjamin G Lamberty, Brenda Morsey, Howard S Fox
The use of antiretroviral (ARV) drugs with central nervous system (CNS) penetration effectiveness (CPE) may be useful in the treatment of HIV-associated neurocognitive disorder (HAND) as well as targeting a CNS reservoir in strategies to achieve a functional cure for HIV. However, increased cognitive deficits are linked to at least one of these drugs (efavirenz). As mitochondrial dysfunction has been found with a number of ARVs, and as such can affect neuronal function, the objective of this study was to assess the effects of ARV with high CPE for toxicological profiles on presynaptic nerve terminal energy metabolism...
September 11, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28891371/an-observational-retrospective-analysis-evaluating-switching-to-raltegravir-plus-abacavir-lamivudine-in-hiv-1-infected-patients-the-oraswiral-study
#6
Laura Galli, Andrea Poli, Camilla Muccini, Nadia Galizzi, Anna Danise, Vincenzo Spagnuolo, Nicola Gianotti, Elisabetta Carini, Adriano Lazzarin, Antonella Castagna
No abstract text is available yet for this article.
September 11, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28867497/bictegravir-emtricitabine-and-tenofovir-alafenamide-versus-dolutegravir-abacavir-and-lamivudine-for-initial-treatment-of-hiv-1-infection-gs-us-380-1489-a-double-blind-multicentre-phase-3-randomised-controlled-non-inferiority-trial
#7
Joel Gallant, Adriano Lazzarin, Anthony Mills, Chloe Orkin, Daniel Podzamczer, Pablo Tebas, Pierre-Marie Girard, Indira Brar, Eric S Daar, David Wohl, Jürgen Rockstroh, Xuelian Wei, Joseph Custodio, Kirsten White, Hal Martin, Andrew Cheng, Erin Quirk
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are recommended components of initial antiretroviral therapy with two nucleoside reverse transcriptase inhibitors. Bictegravir is a novel, potent INSTI with a high in-vitro barrier to resistance and low potential as a perpetrator or victim of clinically relevant drug-drug interactions. We aimed to assess the efficacy and safety of bictegravir coformulated with emtricitabine and tenofovir alafenamide as a fixed-dose combination versus coformulated dolutegravir, abacavir, and lamivudine...
August 31, 2017: Lancet
https://www.readbyqxmd.com/read/28856081/genetic-factors-influencing-drug-induced-liver-injury-do-they-have-a-role-in-prevention-and-diagnosis
#8
REVIEW
Kathleen E Clare, Michael H Miller, John F Dillon
PURPOSE OF REVIEW: The pathogenesis of DILI is currently unknown; however, research has shown strong genetic associations with some DILIs. This paper describes the variant alleles uncovered by GWAS and discusses their potential role as susceptibility biomarkers. RECENT FINDINGS: An association with HLADRB1*15:01 and amoxicillin/clavulanate DILI has been shown by a number of research groups. The presence of the HLA-B*57:01 allele has been associated with an 81-fold increased risk of flucloxacillin DILI...
2017: Current Hepatology Reports
https://www.readbyqxmd.com/read/28835824/acute-recurrent-lymphocytic-meningitis-in-an-immunocompetent-hiv-positive-african-woman-is-it-a-mollaret-s-meningitis-or-not
#9
Katie Tharshana Yoganathan, Soumeya Cherif, Mariam Rashid, Kathir Yoganathan
We report a case of acute recurrent meningitis in an HIV-positive immunocompetent woman. In this case, a 34-year-old African woman with a known HIV infection presented with symptoms of acute meningitis. She was on combination antiretroviral therapy with abacavir, lamivudine, and nevirapine. Her HIV RNA level was <70 IU/mL, and CD4 counts were 640 cells/mm(3). This indicates that she was not immunocompromised. She was febrile on examination, with marked neck stiffness. Her cerebrospinal fluid revealed raised white cell counts with 100% lymphocytes and mildly raised protein...
2017: SAGE open medical case reports
https://www.readbyqxmd.com/read/28825943/weight-gain-in-persons-with-hiv-switched-from-efavirenz-based-to-integrase-strand-transfer-inhibitor-based-regimens
#10
Jamison Norwood, Megan Turner, Carmen Bofill, Peter Rebeiro, Bryan Shepherd, Sally Bebawy, Todd Hulgan, Stephen Raffanti, David W Haas, Timothy R Sterling, John R Koethe
BACKGROUND: With the introduction of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART), persons living with HIV have a potent new treatment option. Recently, providers at our large treatment clinic noted weight gain in several patients switched from efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) to dolutegravir/abacavir/lamivudine (DTG/ABC/3TC). In this study, we evaluated weight change in patients with sustained virologic suppression switched from EFV/TDF/FTC to an INSTI-containing regimen...
August 18, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28782122/nevirapine-patch-testing-in-thai-human-immunodeficiency-virus-infected-patients-with-nevirapine-drug-hypersensitivity
#11
Piyatida Prasertvit, Angkana Chareonyingwattana, Penpun Wattanakrai
BACKGROUND: Antiretroviral drug hypersensitivity in HIV patients is common. Publications have shown that Abacavir (ABC) patch testing is useful in confirming ABC hypersensitivity in 24-50% of cases with a 100% sensitivity of HLA-B*5701 in patch test positive cases. However, Nevirapine (NVP) patch testing has not been reported. OBJECTIVES: (1) To evaluate the usefulness and safety of NVP patch testing in Thai HIV patients with NVP hypersensitivity. (2) To assess the correlation of positive patch tests with HLA-B*3505...
August 6, 2017: Contact Dermatitis
https://www.readbyqxmd.com/read/28772259/high-frequency-of-human-leukocyte-antigen-b-57-01-allele-carriers-among-hiv-infected-patients-in-serbia
#12
Marina Siljic, Dubravka Salemovic, Valentina Cirkovic, Ivana Pesic-Pavlovic, Marija Todorovic, Jovan Ranin, Gordana Dragovic, Djordje Jevtovic, Maja Stanojevic
Abacavir is an effective antiretroviral drug and one of the most commonly used nucleoside reverse transcriptase inhibitors in Serbia. А percentage of the treated patients experience a potentially life-threatening hypersensitivity reaction, which was shown to be associated with the presence of the class I MHC allele, HLA-B*57:01; hence genotyping for HLA-B*57:01 prior to starting abacavir is nowadays recommended in international HIV treatment guidelines. In Serbia, this testing became available in 2013. This study was designed to estimate the prevalence of the HLA-B*57:01 allele in Serbian HIV-1-infected patients...
August 4, 2017: Intervirology
https://www.readbyqxmd.com/read/28753637/collaborative-update-of-a-rule-based-expert-system-for-hiv-1-genotypic-resistance-test-interpretation
#13
Roger Paredes, Philip L Tzou, Gert van Zyl, Geoff Barrow, Ricardo Camacho, Sergio Carmona, Philip M Grant, Ravindra K Gupta, Raph L Hamers, P Richard Harrigan, Michael R Jordan, Rami Kantor, David A Katzenstein, Daniel R Kuritzkes, Frank Maldarelli, Dan Otelea, Carole L Wallis, Jonathan M Schapiro, Robert W Shafer
INTRODUCTION: HIV-1 genotypic resistance test (GRT) interpretation systems (IS) require updates as new studies on HIV-1 drug resistance are published and as treatment guidelines evolve. METHODS: An expert panel was created to provide recommendations for the update of the Stanford HIV Drug Resistance Database (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report, and the drug-resistance interpretations associated with 160 drug-resistance mutation (DRM) pattern-ARV combinations...
2017: PloS One
https://www.readbyqxmd.com/read/28750935/long-acting-intramuscular-cabotegravir-and-rilpivirine-in-adults-with-hiv-1-infection-latte-2-96-week-results-of-a-randomised-open-label-phase-2b-non-inferiority-trial
#14
David A Margolis, Juan Gonzalez-Garcia, Hans-Jürgen Stellbrink, Joseph J Eron, Yazdan Yazdanpanah, Daniel Podzamczer, Thomas Lutz, Jonathan B Angel, Gary J Richmond, Bonaventura Clotet, Felix Gutierrez, Louis Sloan, Marty St Clair, Miranda Murray, Susan L Ford, Joseph Mrus, Parul Patel, Herta Crauwels, Sandy K Griffith, Kenneth C Sutton, David Dorey, Kimberly Y Smith, Peter E Williams, William R Spreen
BACKGROUND: Cabotegravir and rilpivirine are antiretroviral drugs in development as long-acting injectable formulations. The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks. METHODS: In this randomised, phase 2b, open-label study, treatment-naive adults infected with HIV-1 initially received oral cabotegravir 30 mg plus abacavir-lamivudine 600-300 mg once daily. The objective of this study was to select an intramuscular dosing regimen based on a comparison of the antiviral activity, tolerability, and safety of the two intramuscular dosing regimens relative to oral cabotegravir plus abacavir-lamivudine...
July 21, 2017: Lancet
https://www.readbyqxmd.com/read/28748198/abacavir-dolutegravir-lamivudine-triumeq-induced-liver-toxicity-in-a-human-immunodeficiency-virus-infected-patient
#15
Erin S Christensen, Rupali Jain, Alison C Roxby
Drug-induced liver injury related to Triumeq (abacavir/lamivudine/dolutegravir) has not been reported in clinical trials. We report a case of hepatotoxicity related to Triumeq exposure in a human immunodeficiency virus-infected patient. Clinicians should remain aware of the risk for acute and late-onset hepatitis with these agents. Close monitoring is recommended.
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28741965/cost-effectiveness-of-dolutegravir-abacavir-lamivudine-in-hiv-1-treatment-naive-tn-patients-in-france
#16
Gilles Pialoux, Anne-Geneviève Marcelin, Hélène Cawston, Caroline Guilmet, Laurent Finkielsztejn, Audrey Laurisse, Céline Aubin
BACKGROUND: To evaluate the cost-effectiveness of an integrase inhibitor (INI), dolutegravir (DTG), in combination with abacavir (ABC)/lamivudine (3TC) in France, in treatment-naive (TN) HIV adult patients. METHODS: The ARAMIS microsimulation Markov model, evaluates costs and effects of DTG vs. first-line ARVs options including INIs (raltegravir, elvitegravir/c), protease inhibitors (PIs) (darunavir/r, atazanavir/r, lopinavir/r), non-nucleoside reverse transcriptase inhibitors (efavirenz and rilpivirine)...
July 31, 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28732216/development-of-hla-b-57-01-genotyping-real-time-pcr-with-optimized-hydrolysis-probe-design
#17
Hou-Sung Jung, Gregory J Tsongalis, Joel A Lefferts
HLA-B*57:01 genotyping before abacavir (ABC) administration is a standard of care to avoid ABC-driven hypersensitivity reactions. Several HLA-B*57:01 tests have been developed, each with advantages and disadvantages. Some have limited accuracy, require special instrumentation, and/or are labor intensive and expensive. We developed a novel hydrolysis probe-based real-time PCR method of HLA-B*57:01 genotyping. Primer and probes were designed based on published sequence variations in exon 3 of HLA-B that distinguish HLA-B*57:01 from ABC-insensitive alleles such as HLA-B*57:03 and HLA-B*58:01...
July 18, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28729158/fixed-dose-combination-dolutegravir-abacavir-and-lamivudine-versus-ritonavir-boosted-atazanavir-plus-tenofovir-disoproxil-fumarate-and-emtricitabine-in-previously-untreated-women-with-hiv-1-infection-aria-week-48-results-from-a-randomised-open-label-non-inferiority
#18
Catherine Orrell, Debbie P Hagins, Elena Belonosova, Norma Porteiro, Sharon Walmsley, Vicenç Falcó, Choy Y Man, Alicia Aylott, Ann M Buchanan, Brian Wynne, Cindy Vavro, Michael Aboud, Kimberly Y Smith
BACKGROUND: Dolutegravir is a once-daily integrase strand transfer inhibitor with no need for pharmacokinetic boosting that is approved for the treatment of HIV-1 infection. Because women are often under-represented in HIV clinical trials, we addressed the safety and efficacy of dolutegravir in women with HIV-1. METHODS: The ARIA study is a randomised, open-label, multicentre, active-controlled, parallel-group, non-inferiority phase 3b study done in 86 hospital and university infectious disease clinics, local health clinics, and private infectious disease clinics in 12 countries and one US territory, in North America, South America, Europe, Africa, and Asia...
July 17, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28701018/bioactive-triterpenoids-from-the-leaves-and-twigs-of-lithocarpus-litseifolius-and-l-%C3%A2-corneus
#19
Yuan-Bin Cheng, Fan-Jin Liu, Chih-Hsin Wang, Tsong-Long Hwang, Yung-Fong Tsai, Chia-Hung Yen, Hui-Chun Wang, Yen-Hsueh Tseng, Ching-Te Chien, Yi-Ming Arthur Chen, Fang-Rong Chang, Yang-Chang Wu
Phytochemical investigation of the leaves and twigs of Lithocarpus litseifolius and Lithocarpus corneus resulted in the isolation of four new triterpenoids (1-4), three triterpenoids (5-7) isolated from a natural source for the first time, and six known compounds (8-13). In addition, four known triterpenoids (14-17) were isolated from L. corneus. Compound 1 is a 3,4-seco-lupane-type triterpenoid, and compounds 2-4 are lupane-type triterpenoids in different oxidation states. The structures of all isolated compounds were identified by spectroscopic methods, especially NMR and mass spectrometry data...
July 12, 2017: Planta Medica
https://www.readbyqxmd.com/read/28696229/mdr1-and-bcrp-transporter-mediated-drug-drug-interaction-between-rilpivirine-and-abacavir-and-effect-on-intestinal-absorption
#20
Josef Reznicek, Martina Ceckova, Zuzana Ptackova, Ondrej Martinec, Lenka Tupova, Lukas Cerveny, Frantisek Staud
Rilpivirine (TMC278) is a highly potent nonnucleoside reverse transcriptase inhibitor (NNRTI) representing an effective component of combination antiretroviral therapy (cART) in the treatment of HIV-positive patients. Many antiretroviral drugs commonly used in cART are substrates of ATP-binding cassette (ABC) and/or solute carrier (SLC) drug transporters and, therefore, are prone to pharmacokinetic drug-drug interactions (DDIs). The aim of our study was to evaluate rilpivirine interactions with abacavir and lamivudine on selected ABC and SLC transporters in vitro and assess its importance for pharmacokinetics in vivo Using accumulation assays in MDCK cells overexpressing selected ABC or SLC drug transporters, we revealed rilpivirine as a potent inhibitor of MDR1 and BCRP, but not MRP2, OCT1, OCT2, or MATE1...
September 2017: Antimicrobial Agents and Chemotherapy
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