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https://www.readbyqxmd.com/read/29782330/a-transgenic-mouse-model-for-hla-b-57-01-linked-abacavir-drug-tolerance-and-reactivity
#1
Marco Cardone, Karla Garcia, Mulualem E Tilahun, Lisa F Boyd, Sintayehu Gebreyohannes, Masahide Yano, Gregory Roderiquez, Adovi D Akue, Leslie Juengst, Elliot Mattson, Suryatheja Ananthula, Kannan Natarajan, Montserrat Puig, David H Margulies, Michael A Norcross
Adverse drug reactions (ADRs) are a major obstacle to drug development, and some of these, including hypersensitivity reactions to the HIV reverse transcriptase inhibitor abacavir (ABC), are associated with HLA alleles, particularly HLA-B*57:01. However, not all HLA-B*57:01+ patients develop ADRs, suggesting that in addition to the HLA genetic risk, other factors may influence the outcome of the response to the drug. To study HLA-linked ADRs in vivo, we generated HLA-B*57:01-Tg mice and show that, although ABC activated Tg mouse CD8+ T cells in vitro in a HLA-B*57:01-dependent manner, the drug was tolerated in vivo...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29781810/active-suppression-rather-than-ignorance-tolerance-to-abacavir-induced-hla-b-57-01-peptide-repertoire-alteration
#2
Elizabeth J Phillips, Simon A Mallal
The discovery of HLA-B*57:01-associated abacavir hypersensitivity is a translational success story that eliminated adverse reactions to abacavir through pretreatment screening and defined a mechanistic model of an altered peptide repertoire. In this issue of the JCI, Cardone et al. have developed an HLA-B*57:01-transgenic mouse model and demonstrated that CD4+ T cells play a key role in mediating tolerance to the dramatically altered endogenous peptide repertoire induced by abacavir and postulate a known mechanism by which CD4+ T cells suppress DC maturation...
May 21, 2018: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29771285/increased-dolutegravir-peak-concentrations-in-people-living-with-hiv-aged-60-and-over-and-analysis-of-sleep-quality-and-cognition
#3
Emilie R Elliot, Xinzhu Wang, Suveer Singh, Bryony Simmons, Jaime H Vera, Robert F Miller, Colin Fitzpatrick, Graeme Moyle, Myra McClure, Marta Boffito
Background: Demographic data show an increasingly aging HIV population worldwide. Recent concerns over dolutegravir-related neuropsychiatric toxicity have emerged, particularly amongst older HIV patients. We describe the pharmacokinetics (PK) of dolutegravir (DTG) 50mg once daily in people living with HIV (PLWH) aged 60 and older. Additionally, to address the call for prospective neuropsychiatric toxicodynamic data, we evaluate changes in sleep quality and cognitive function after switching to abacavir (ABC)/lamivudine (3TC)/DTG, over 6 months in this population...
May 16, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29766019/abacavir-use-and-risk-for-myocardial-infarction-and-cardiovascular-events-pooled-analysis-of-data-from-clinical-trials
#4
Cassandra Nan, Mark Shaefer, Rimgaile Urbaityte, James Oyee, Judy Hopking, Leigh Ragone, Teodora Perger, Beta Win, Harald Vangerow, Cynthia McCoig, Vani Vannappagari
Background: Some observational studies and randomized controlled trials (RCTs) have suggested an association between abacavir (ABC) use and myocardial infarction (MI), whereas others have not. Methods: This pooled analysis of 66 phase II-IV RCTs estimates exposure-adjusted incidence rates (IRs) and relative rates (RRs) of MI and cardiovascular events (CVEs) in participants receiving ABC- and non-ABC-containing combination antiretroviral therapy (cART). The primary analysis of MI included ABC-randomized trials with ≥48-week follow-up...
May 2018: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/29759422/executive-summary-of-the-gesida-national-aids-plan-consensus-document-on-antiretroviral-therapy-in-adults-infected-by-the-human-immunodeficiency-virus-updated-january-2018
#5
(no author information available yet)
This update to the document on antiretroviral therapy (ART) in adults, which has been prepared jointly by GeSIDA and the Spanish National AIDS Plan for the last two decades, supersedes the document published in 2017.1 The update provides physicians treating HIV-1-infected adults with evidence-based recommendations to guide their therapeutic decisions. The main difference with respect to the previous document concerns recommended initial ART regimens, only three of which are maintained as preferential. All three include dolutegravir or raltegravir, together with emtricitabine/tenofovir alafenamide or abacavir/lamivudine...
May 11, 2018: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/29718247/emerging-resistance-mutations-in-pi-naive-patients-failing-an-atazanavir-based-regimen-anrs-multicentre-observational-study
#6
S Lambert-Niclot, M Grude, M L Chaix, C Charpentier, S Reigadas, H Le Guillou-Guillemette, A Rodallec, C Amiel, A Maillard, J Dufayard, T Mourez, A Mirand, J Guinard, B Montes, S Vallet, A G Marcelin, D Descamps, P Flandre, C Delaugerre, L Morand-Joubert
Background: Atazanavir is a PI widely used as a third agent in combination ART. We aimed to determine the prevalence and the patterns of resistance in PI-naive patients failing on an atazanavir-based regimen. Methods: We analysed patients failing on an atazanavir-containing regimen used as a first line of PI therapy. We compared the sequences of reverse transcriptase and protease before the introduction of atazanavir and at failure [two consecutive viral loads (VLs) >50 copies/mL]...
April 27, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29685693/effect-of-aspirin-treatment-on-abacavir-associated-platelet-hyperreactivity-in-hiv-infected-patients
#7
Emanuela Falcinelli, Daniela Francisci, Elisabetta Schiaroli, Pietro Minuz, Sara Orsini, Lisa Malincarne, Manuela Sebastiano, Anna Maria Mezzasoma, Maria Bruna Pasticci, Giuseppe Guglielmini, Franco Baldelli, Paolo Gresele
BACKGROUND: Ischemic cardiovascular events are a relevant cause of morbidity and mortality in HIV-infected patients. Use of abacavir (ABC), a nucleoside analog reverse transcriptase inhibitor, has been associated with increased risk of myocardial infarction (MI) and with platelet hyperreactivity. We explored whether low-dose aspirin reduces in vivo platelet activation and platelet hyperreactivity induced by ABC in HIV-infected subjects. METHODS AND RESULTS: In a randomized, placebo-controlled, cross-over study forty HIV-infected patients with ABC-associated platelet hyperreactivity, defined by a score based on laboratory variables reflecting in vivo platelet activation and ex vivo platelet hyperresponsiveness, were randomized to aspirin 100 mg daily for 15 days with subsequent cross-over to placebo for additional 15 days or placebo for 15 days with subsequent cross-over to aspirin for further 15 days...
April 12, 2018: International Journal of Cardiology
https://www.readbyqxmd.com/read/29682780/pharmacogenomic-information-in-the-warning-section-of-drug-labels-a-comparison-between-labels-in-the-united-states-and-those-in-five-other-countries-regions
#8
T Imatoh, K Sai, Y Saito
WHAT IS KNOWN AND OBJECTIVE: Clinically validated pharmacogenomic information useful for patient selection and/or dose adjustment is included in drug labels. However, the label information may differ among countries. This commentary summarizes the pharmacogenomic information on drug labels in different countries. COMMENT: We selected six drugs, namely, clopidogrel, atomoxetine, irinotecan, mercaptopurine, abacavir and carbamazepine and compared the pharmacogenomic information in the "Warning" section of these drug labels in the United States and 5 other countries/regions...
April 22, 2018: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/29656449/regimen-durability-in-hiv-infected-children-and-adolescents-initiating-first-line-art-in-a-large-public-sector-hiv-cohort-in-south-africa
#9
Rachael Bonawitz, Alana T Brennan, Lawrence Long, Timothy Heeren, Mhairi Maskew, Ian Sanne, Matthew P Fox
INTRODUCTION: In April 2010 tenofovir and abacavir replaced stavudine in public-sector first-line antiretroviral therapy (ART) for children under 20 years old in South Africa. The association of both abacavir and tenofovir with fewer side-effects and toxicities compared to stavudine could translate to increased durability of tenofovir or abacavir-based regimens. We evaluated changes over time in regimen durability for pediatric patients 3 to 19 years of age at 8 public sector clinics in Johannesburg, South Africa...
April 15, 2018: Tropical Medicine & International Health: TM & IH
https://www.readbyqxmd.com/read/29628511/dolutegravir-neuropsychiatric-adverse-events-specific-drug-effect-or-class-effect
#10
Jean Cyr Yombi
Integrase strand transfer inhibitors (INSTIs) are a newer class of antiretroviral treatment for HIV-infected patient. INSTIs currently available for use are raltegravir, elvitegravir, dolutegravir (DTG), and bictegravir. Clinical studies using INSTIs have demonstrated an 80-90% efficiency in treating HIV-positive antiretroviral therapy - naive patients. They are recommended by internatioal guidelines as the preferred agents for the first-line regimen. INSTIs have also been demonstrated as safe and tolerable...
January 2018: AIDS Reviews
https://www.readbyqxmd.com/read/29623097/renal-effects-of-non-tenofovir-antiretroviral-therapy-in-patients-living-with-hiv
#11
REVIEW
Milena M McLaughlin, Aimee J Guerrero, Andrew Merker
A review of literature published regarding non-tenofovir antiretroviral agents causing renal adverse effects was conducted. The literature involving renal adverse effects and antiretroviral therapy is most robust with protease inhibitors, specifically atazanavir and indinavir, and includes reports of crystalluria, leukocyturia, nephritis, nephrolithiasis, nephropathy and urolithiasis. Several case reports describe potential nephropathy (including Fanconi syndrome) secondary to administration of abacavir, didanosine, lamivudine and stavudine...
2018: Drugs in Context
https://www.readbyqxmd.com/read/29592840/doravirine-versus-ritonavir-boosted-darunavir-in-antiretroviral-naive-adults-with-hiv-1-drive-forward-48-week-results-of-a-randomised-double-blind-phase-3-non-inferiority-trial
#12
Jean-Michel Molina, Kathleen Squires, Paul E Sax, Pedro Cahn, Johan Lombaard, Edwin DeJesus, Ming-Tain Lai, Xia Xu, Anthony Rodgers, Lisa Lupinacci, Sushma Kumar, Peter Sklar, Bach-Yen Nguyen, George J Hanna, Carey Hwang
BACKGROUND: Doravirine is a novel non-nucleoside reverse transcriptase inhibitor (NNRTI) with a pharmacokinetic profile supporting once-daily dosing, and potent in-vitro activity against the most common NNRTI-resistant HIV-1 variants. We compared doravirine with ritonavir-boosted darunavir, when both were given with two nucleoside reverse transcriptase inhibitors (NRTIs), in adults with previously untreated HIV-1 infection. METHODS: In this randomised, controlled, double-blind, multicentre, non-inferiority trial, adults with HIV-1 infection were screened and enrolled at 125 clinical centres in 15 countries...
March 23, 2018: Lancet HIV
https://www.readbyqxmd.com/read/29568194/analytical-method-development-and-validation-for-the-simultaneous-estimation-of-abacavir-and-lamivudine-by-reversed-phase-high-performance-liquid-chromatography-in-bulk-and-tablet-dosage-forms
#13
Sufiyan Ahmad Raees Ahmad, Lalit Patil, Mohammed Rageeb Mohammed Usman, Mohammad Imran, Rashid Akhtar
Objective: A simple rapid, accurate, precise, and reproducible validated reverse phase high performance liquid chromatography (HPLC) method was developed for the determination of Abacavir (ABAC) and Lamivudine (LAMI) in bulk and tablet dosage forms. Methods: The quantification was carried out using Symmetry Premsil C18 (250 mm × 4.6 mm, 5 μm) column run in isocratic way using mobile phase comprising methanol: water (0.05% orthophosphoric acid with pH 3) 83:17 v/v and a detection wavelength of 245 nm and injection volume of 20 μl, with a flow rate of 1 ml/min...
January 2018: Pharmacognosy Research
https://www.readbyqxmd.com/read/29564734/drug-induced-skin-adverse-reactions-the-role-of-pharmacogenomics-in-their-prevention
#14
REVIEW
Kalliopi Gerogianni, Aspasia Tsezou, Konstantinos Dimas
Adverse drug reactions (ADRs) affect many patients and remain a major public health problem, as they are a common cause of morbidity and mortality. It is estimated that ADRs are responsible for about 6% of hospital admissions and about 9% of hospitalization costs. Skin is the organ that is most frequently involved in ADRs. Drug-induced skin injuries vary from mild maculopapular eruptions (MPE) to severe cutaneous adverse reactions (SCARs) that are potentially life threatening. Genetic factors have been suggested to contribute to these SCARs, and most significant genetic associations have been identified in the major histocompatibility complex (MHC) genes...
March 21, 2018: Molecular Diagnosis & Therapy
https://www.readbyqxmd.com/read/29533918/intentional-overdose-of-dolutegravir-abacavir-lamivudine-triumeq-in-a-26-year-old-man
#15
Paul Mel van Dam, Mark Wl van Geffen, Thomas Ra Havenith, Dirk Posthouwer
Triumeq is a single-tablet regimen for patients with HIV infection comprising dolutegravir, abacavir and lamivudine. Overdoses with Triumeq have not been reported previously. We present a case of a 26-year-old man who presented to our hospital after intentionally ingesting 30 tablets of Triumeq. An intoxication with Triumeq can lead to several side effects. An overdose of abacavir and lamivudine can cause mitochondrial toxicity and lactic acidosis. An intoxication with dolutegravir appears to be relatively harmless...
March 13, 2018: Antiviral Therapy
https://www.readbyqxmd.com/read/29524887/lc-ms-ms-determination-of-antiretroviral-drugs-in-influents-and-effluents-from-wastewater-treatment-plants-in-kwazulu-natal-south-africa
#16
Ovokeroye A Abafe, Jana Späth, Jerker Fick, Stina Jansson, Chris Buckley, Annegret Stark, Bjoern Pietruschka, Bice S Martincigh
South Africa has the largest occurrence of the human immune deficiency virus (HIV) in the world but has also implemented the largest antiretroviral (ARV) treatment programme. It was therefore of interest to determine the presence and concentrations of commonly used antiretroviral drugs (ARVDs) and, also, to determine the capabilities of wastewater treatment plants (WWTPs) for removing ARVDs. To this end, a surrogate standard based LC-MS/MS method was optimized and applied for the detection of thirteen ARVDs used in the treatment and management of HIV/acquired immune deficiency syndrome (HIV/AIDS) in two major and one modular WWTP in the eThekwini Municipality in KwaZulu-Natal, South Africa...
June 2018: Chemosphere
https://www.readbyqxmd.com/read/29518644/simultaneous-quantification-of-intracellular-lamivudine-and-abacavir-triphosphate-metabolites-by-lc-ms-ms
#17
Nagsen Gautam, Zhiyi Lin, Mary G Banoub, Nathan A Smith, Audai Maayah, JoEllyn McMillan, Howard E Gendelman, Yazen Alnouti
Nucleoside reverse transcriptase inhibitors (NRTIs) require intracellular phosphorylation to active triphosphate (TP) nucleotide metabolites before they can inhibit the HIV reverse transcriptase. However, monitoring these pharmacologically active TP metabolites is challenging due to their instability and their low concentrations at the pg/ml levels in blood and tissues. The combination of lamivudine (3TC) and abacavir (ABC) is one of the first lines for HIV therapy. Therefore, a sensitive, selective, accurate, and precise LC-MS/MS method was developed and validated for the simultaneous quantification of 3TC- and ABC-TP metabolites in mouse blood and tissues...
May 10, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29500066/a-kinetically-controlled-isothermal-method-for-the-detection-of-single-nucleotide-mismatches
#18
Yoshiaki Masaki, Devon Cayer, Ryan McBride, M Reza Ghadiri
We describe an isothermal, enzyme-free method to detect single nucleotide differences between oligonucleotides of close homology. The approach exploits kinetic differences in toe-hold-mediated, nucleic acid strand-displacement reactions to detect single nucleotide polymorphisms (SNPs) with essentially "digital" precision. The theoretical underpinning, experimental analyses, predictability, and accuracy of this new method are reported. We demonstrate detection of biologically relevant SNPs and single nucleotide differences in the let-7 family of microRNAs...
February 14, 2018: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29475804/tenofovir-alafenamide-plus-emtricitabine-versus-abacavir-plus-lamivudine-for-treatment-of-virologically-suppressed-hiv-1-infected-adults-a-randomised-double-blind-active-controlled-non-inferiority-phase-3-trial
#19
Alan Winston, Frank A Post, Edwin DeJesus, Daniel Podzamczer, Giovanni Di Perri, Vicente Estrada, François Raffi, Peter Ruane, Paula Peyrani, Gordon Crofoot, Patrick W G Mallon, Francesco Castelli, Mingjin Yan, Stephanie Cox, Moupali Das, Andrew Cheng, Martin S Rhee
BACKGROUND: Abacavir and tenofovir alafenamide offer reduced bone toxicity compared with tenofovir disoproxil fumarate. We aimed to compare safety and efficacy of tenofovir alafenamide plus emtricitabine with that of abacavir plus lamivudine. METHODS: In this randomised, double-blind, active-controlled, non-inferiority phase 3 trial, HIV-1-positive adults (≥18 years) were screened at 79 sites in 11 countries in North America and Europe. Eligible participants were virologically suppressed (HIV-1 RNA <50 copies per mL) and on a stable three-drug regimen containing abacavir plus lamivudine...
April 2018: Lancet HIV
https://www.readbyqxmd.com/read/29451870/long-term-efficacy-and-safety-of-rilpivirine-plus-abacavir-and-lamivudine-in-hiv-1-infected-patients-with-undetectable-viral-load
#20
Nadia Galizzi, Laura Galli, Andrea Poli, Nicola Gianotti, Elisabetta Carini, Alba Bigoloni, Giuseppe Tambussi, Silvia Nozza, Adriano Lazzarin, Antonella Castagna, Daniela Mancusi, Roberta Termini
INTRODUCTION: A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen. METHODS: Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015...
2018: PloS One
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