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https://www.readbyqxmd.com/read/28732216/development-of-hla-b-57-01-genotyping-real-time-pcr-with-optimized-hydrolysis-probe-design
#1
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
#2
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
#3
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-effect-on-intestinal-absorption
#4
Josef Reznicek, Martina Ceckova, Zuzana Ptackova, Ondrej Martinec, Lenka Tupova, Lukas Cerveny, Frantisek Staud
Rilpivirine (TMC278) is a highly potent second-generation non-nucleoside 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, 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 vivoUsing 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...
July 10, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28695285/the-role-of-hla-genes-in-pharmacogenomics-unravelling-hla-associated-adverse-drug-reactions
#5
REVIEW
Patricia T Illing, Anthony W Purcell, James McCluskey
Genetic polymorphism in the genes encoding the human leukocyte antigen (HLA) molecules enables presentation of a wide range peptide ligands thus maximising immune surveillance of pathogens. A consequence of the diversification of the HLA Ag-binding pocket is the enhanced opportunity for off-target binding of small drugs by HLA molecules, with subsequent immune reactivity. These potential off-target interactions are 'set up' to generate T cell-mediated adverse drug reactions even though the precise mechanisms of most HLA-drug interactions are still poorly understood...
July 10, 2017: Immunogenetics
https://www.readbyqxmd.com/read/28686654/a-retrospective-case-cohort-study-comparing-treatment-outcomes-in-abacavir-versus-stavudine-containing-first-line-antiretroviral-treatment-regimens-in-children-3yrs-old-at-a-paediatric-programme-based-in-soweto-south-africa
#6
Haseena Cassim, Kennedy Otwombe, Erica Lazarus, Afaaf Liberty, Glenda E Gray, Oppel B W Greeff, Avy Violari
INTRODUCTION: The current World Health Organization guideline for first line antiretroviral therapy (ART) in HIV-infected children recommends the use of abacavir and lamivudine as nucleoside backbones and no longer includes stavudine. We compared treatment outcomes with abacavir (ABC) versus stavudine (d4T) in a cohort of HIV-1 infected children 6 and 12 months after antiretroviral therapy was initiated. METHODS: This was a retrospective case-cohort study, using programmatic data from children enrolled in the Paediatric Wellness Programme at the Perinatal HIV Research Unit in Soweto, South Africa between 2005 and 2013...
2017: PloS One
https://www.readbyqxmd.com/read/28686208/structural-elements-recognized-by-abacavir-induced-t-cells
#7
Daniel Yerly, Yuri Andreiw Pompeu, Ryan J Schutte, Klara K Eriksson, Anette Strhyn, Austin W Bracey, Soren Buus, David A Ostrov
Adverse drug reactions are one of the leading causes of morbidity and mortality in health care worldwide. Human leukocyte antigen (HLA) alleles have been strongly associated with drug hypersensitivities, and the causative drugs have been shown to stimulate specific T cells at the sites of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs) in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin) presented in the context of small molecule drugs are not well studied...
July 7, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28664942/darunavir-stands-up-as-preferred-hiv-protease-inhibitor
#8
Josep Mallolas
Current antiretroviral therapy reaches and maintains viral suppression over the years in more than 90% of treated HIV-infected individuals. Although integrase inhibitors are the preferred third agent in antiretroviral therapy in the current guidelines, rilpivirine, a non-nucleoside reverse transcrip- tase inhibitor, and darunavir (DRV), a second-generation protease inhibitor, are the preferred third companion to be used along with a backbone of two nucleos(t)ide reverse transcriptase inhibitors as first-line triple HIV combination treatment...
April 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28639996/should-abacavir-be-a-first-line-alternative-for-adults-with-hiv-in-sub-saharan-africa
#9
Guinevere Q Lee, Suzanne McCluskey, Yap Boum, Peter W Hunt, Jeffrey N Martin, David R Bangsberg, Xiaojiang Gao, P Richard Harrigan, Jessica E Haberer, Mark J Siedner
Despite a poor toxicity profile, zidovudine supersedes abacavir as an alternative first-line agent in most international treatment-guidelines due to concerns about HLA-B*57:01-related abacavir-hypersensitivity. We detected one case of HLA-B*57:01 carriage among 513 HIV-infected individuals in Uganda, which, in combination with prior reports, supports the safety of abacavir in the region.
June 19, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28627771/clinical-experience-with-the-integrase-inhibitors-dolutegravir-and-elvitegravir-in-hiv-infected-patients-efficacy-safety-and-tolerance
#10
Purificación Cid-Silva, Josep M Llibre, Noelia Fernández-Bargiela, Luis Margusino-Framiñán, Vanesa Balboa-Barreiro, Berta Pernas-Souto, Isabel Martín-Herranz, Ángeles Castro-Iglesias, Eva Poveda
Two integrase inhibitors (INSTIs), dolutegravir (DTG) and elvitegravir/cobicistat (EVG/COBI), have joined recently the pharmacotherapy arsenal against HIV. This study evaluated the efficacy and tolerability of these INSTIs in the last two years. A retrospective observational study in patients who started DTG or EVG/COBI from January 2015 to January 2017 at a reference hospital in north-western Spain was done. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed with SPSS software...
June 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28594295/long-term-outcomes-of-second-line-antiretroviral-treatment-in-an-adult-and-adolescent-cohort-in-myanmar
#11
Nang Thu Thu Kyaw, Ajay M V Kumar, Myo Minn Oo, Htun Nyunt Oo, Khine Wut Yee Kyaw, Soe Thiha, Thet Ko Aung, Than Win, Yin Yin Mon, Anthony D Harries
BACKGROUND: Myanmar has a high burden of Human Immunodeficiency Virus (HIV) and second-line antiretroviral treatment (ART) has been available since 2008 in the public health sector. However, there have been no published data about the outcomes of such patients until now. OBJECTIVE: To assess the treatment and programmatic outcomes and factors associated with unfavorable outcomes (treatment failure, death and loss to follow-up from care) among people living with HIV (aged ≥ 10 years) receiving protease inhibitor-based second-line ART under the Integrated HIV Care Program in Myanmar between October 2008 and June 2015...
2017: Global Health Action
https://www.readbyqxmd.com/read/28582463/drug-resistance-testing-through-remote-genotyping-and-predicted-treatment-options-in-human-immunodeficiency-virus-type-1-infected-tanzanian-subjects-failing-first-or-second-line-antiretroviral-therapy
#12
Jenny Svärd, Sabina Mugusi, Doreen Mloka, Ujjwal Neogi, Genny Meini, Ferdinand Mugusi, Francesca Incardona, Maurizio Zazzi, Anders Sönnerborg
INTRODUCTION: Antiretroviral therapy (ART) has been successfully introduced in low-middle income countries. However an increasing rate of ART failure with resistant virus is reported. We therefore described the pattern of drug resistance mutations at antiretroviral treatment (ART) failure in a real-life Tanzanian setting using the remote genotyping procedure and thereafter predicted future treatment options using rule-based algorithm and the EuResist bioinformatics predictive engine. According to national guidelines, the default first-line regimen is tenofovir + lamivudine + efavirenz, but variations including nevirapine, stavudine or emtricitabine can be considered...
2017: PloS One
https://www.readbyqxmd.com/read/28579016/executive-summary-of-the-gesida-national-aids-plan-consensus-document-on-antiretroviral-therapy-in-adults-infected-by-the-human-immunodeficiency-virus-updated-january-2017
#13
(no author information available yet)
Antiretroviral therapy (ART) is recommended for all patients infected by HIV-1. The objective of ART is to achieve an undetectable plasma viral load (PVL). Initial ART should be based on a combination of 3 drugs, including 2 nucleoside reverse transcriptase inhibitors (tenofovir in either of its two formulations plus emtricitabine or abacavir plus lamivudine) and another drug from a different family. Four of the recommended regimens, all of which have an integrase inhibitor as the third drug (dolutegravir, elvitegravir boosted with cobicistat or raltegravir), are considered preferential, whereas a further 3 regimens (based on elvitegravir/cobicistat, rilpivirine, or darunavir boosted with cobicistat or ritonavir) are considered alternatives...
May 31, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/28537935/cardiovascular-toxicity-of-abacavir-a-clinical-controversy-in-need-of-a-pharmacological-explanation
#14
Angeles Alvarez, Samuel Orden, Isabel Andújar, Victor Collado-Diaz, Sara Núñez-Delgado, Maria Jose Galindo, Vicente Estrada, Nadezda Apostolova, Juan V Esplugues
: There is a long-lasting controversy surrounding an association between Abacavir (ABC) and an increased risk of cardiovascular (CV) disease in HIV-positive subjects. While differing in their specifics, a number of published cohort studies and clinical trials support such an association, usually relating it to recent exposure to the drug, independently of traditional predisposing factors. However, other clinical trials have failed to reveal such a relation, and have pointed to methodological differences to explain discrepancies...
May 23, 2017: AIDS
https://www.readbyqxmd.com/read/28520610/candidates-for-inclusion-in-a-universal-antiretroviral-regimen-dolutegravir
#15
Pedro Cahn
PURPOSE OF REVIEW: The review addresses the role of dolutegravir (DTG) in first-line therapy. In the era of test and treat, where United Nations AIDS Program and WHO have set the ambitious targets of 90/90/90, new efficacious, well tolerated, and simple therapeutic options are needed. RECENT FINDINGS: DTG has been tested in large clinical trials in treatment-naïve patients, showing noninferiority to raltegravir and superiority compared with efavirenz and ritonavir-boosted darunavir, respectively...
July 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28484509/factors-associated-with-pre-treatment-hiv-rna-application-for-the-use-of-abacavir-and-rilpivirine-as-the-first-line-regimen-for-hiv-infected-patients-in-resource-limited-settings
#16
Sasisopin Kiertiburanakul, David Boettiger, Oon Tek Ng, Nguyen Van Kinh, Tuti Parwati Merati, Anchalee Avihingsanon, Wing-Wai Wong, Man Po Lee, Romanee Chaiwarith, Adeeba Kamarulzaman, Pacharee Kantipong, Fujie Zhang, Jun Yong Choi, Nagalingeswaran Kumarasamy, Rossana Ditangco, Do Duy Cuong, Shinichi Oka, Benedict Lim Heng Sim, Winai Ratanasuwan, Penh Sun Ly, Evy Yunihastuti, Sanjay Pujari, Jeremy L Ross, Matthew Law, Somnuek Sungkanuparph
BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome...
2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28476131/factors-associated-with-pre-treatment-hiv-rna-application-for-the-use-of-abacavir-and-rilpivirine-as-the-first-line-regimen-for-hiv-infected-patients-in-resource-limited-settings
#17
Sasisopin Kiertiburanakul, David Boettiger, Oon Tek Ng, Nguyen Van Kinh, Tuti Parwati Merati, Anchalee Avihingsanon, Wing-Wai Wong, Man Po Lee, Romanee Chaiwarith, Adeeba Kamarulzaman, Pacharee Kantipong, Fujie Zhang, Jun Yong Choi, Nagalingeswaran Kumarasamy, Rossana Ditangco, Do Duy Cuong, Shinichi Oka, Benedict Lim Heng Sim, Winai Ratanasuwan, Penh Sun Ly, Evy Yunihastuti, Sanjay Pujari, Jeremy L Ross, Matthew Law, Somnuek Sungkanuparph
BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome...
May 5, 2017: AIDS Research and Therapy
https://www.readbyqxmd.com/read/28470014/risk-of-acute-liver-injury-with-antiretroviral-therapy-by-viral-hepatitis-status
#18
Charitha Gowda, Craig W Newcomb, Qing Liu, Dena M Carbonari, James D Lewis, Kimberly A Forde, David S Goldberg, K Rajender Reddy, Jason A Roy, Amy R Marks, Jennifer L Schneider, Jay R Kostman, Janet P Tate, Joseph K Lim, Amy C Justice, Matthew Bidwell Goetz, Douglas A Corley, Vincent Lo Re
BACKGROUND: The risk of hepatotoxicity with antiretroviral therapy (ART) remains unknown. We determined the comparative risk of acute liver injury (ALI) for antiretroviral drugs, classes, and regimens, by viral hepatitis status. METHODS: We followed a cohort of 10 083 human immunodeficiency virus (HIV)-infected persons in Kaiser Permanente Northern California (n = 2099) from 2004 to 2010 and the Veterans Aging Cohort Study (n = 7984) from 2004 to 2012. Within the first year of ART, we determined occurrence of (1) liver aminotransferases >200 U/L and (2) severe ALI (coagulopathy with hyperbilirubinemia)...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28463877/timing-of-pregnancy-postpartum-risk-of-virologic-failure-and-loss-to-follow-up-among-hiv-positive-women
#19
Dorina Onoya, Tembeka Sineke, Alana T Brennan, Lawrence Long, Matthew P Fox
OBJECTIVES: We assessed the association between the timing of pregnancy with the risk of postpartum virologic failure and loss from HIV care in South Africa. DESIGN: This is a retrospective cohort study of 6306 HIV-positive women aged 15-49 at antiretroviral therapy (ART) initiation, initiated on ART between January 2004 and December 2013 in Johannesburg, South Africa. METHODS: The incidence of virologic failure (two consecutive viral load measurements of >1000 copies/ml) and loss to follow-up (>3 months late for a visit) during 24 months postpartum were assessed using Cox proportional hazards modelling...
July 17, 2017: AIDS
https://www.readbyqxmd.com/read/28458904/fluticasone-furoate-induced-iatrogenic-cushing-syndrome-in-a-pediatric-patient-receiving-anti-retroviral-therapy
#20
S A A van den Berg, N E van 't Veer, J M A Emmen, R H T van Beek
SUMMARY: We present a case of iatrogenic Cushing's syndrome, induced by treatment with fluticasone furoate (1-2 dd, 27.5 µg in each nostril) in a pediatric patient treated for congenital HIV. The pediatric patient described in this case report is a young girl of African descent, treated for congenital HIV with a combination therapy of Lopinavir/Ritonavir (1 dd 320/80 mg), Lamivudine (1 dd 160 mg) and Abacavir (1 dd 320 mg). Our pediatric patient presented with typical Cushingoid features (i...
2017: Endocrinology, Diabetes & Metabolism Case Reports
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