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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
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...
February 20, 2018: Chemosphere
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...
February 20, 2018: Journal of Pharmaceutical and Biomedical Analysis
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
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...
February 20, 2018: Lancet HIV
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
A Calcagno, C Pinnetti, A De Nicolò, E Scarvaglieri, M Gisslen, M Tempestilli, A D'Avolio A, V Fedele, G Di Perri, A Antinori, S Bonora
Abacavir is a widely used nucleotide reverse transcriptase inhibitor whose cerebrospinal fluid (CSF) exposure has been previously assessed in twice-daily recipients. We studied abacavir CSF concentrations in 61 and 9 HIV-positive once-daily and twice-daily abacavir intakers. Patients on once-daily abacavir had higher plasma and CSF concentrations (96 vs. 22 ng/mL, p=0.038 and 123 vs. 49 ng/mL, p=0.038) but similar CSF-to-plasma ratios (0.8 vs. 0.5, p=0.500). CSF abacavir concentrations were adequate in once-daily receiving patients...
February 14, 2018: British Journal of Clinical Pharmacology
Jane A O'Halloran, Eimear Dunne, Willard Tinago, Stephanie Denieffe, Dermot Kenny, Patrick W G Mallon
OBJECTIVES: Altered platelet function has been proposed as an underlying mechanism to explain increased risk of myocardial infarction in people living with HIV associated with use of the nucleoside reverse transcriptase inhibitor abacavir (ABC). We aimed to examine changes in platelet biomarkers in people living with HIV switching from ABC. METHODS: In a prospective, 48-week substudy of virally suppressed HIV-1-positive subjects randomized to remain on ABC/lamivudine (ABC/3TC) or switch to tenofovir disoproxil fumarate/emtricitabine, we measured soluble glycoprotein VI (sGPVI), soluble P-selectin, soluble CD40 ligand and von Willebrand factor in plasma collected over time and assessed differences using mixed effect models...
February 12, 2018: AIDS
Borja Mora-Peris, George Bouliotis, Kulasegaram Ranjababu, Amanda Clarke, Frank A Post, Mark Nelson, Laura Burgess, Juan Tiraboschi, Saye Khoo, Steve Taylor, Deborah Ashby, Alan Winston
BACKGROUND: Maraviroc-intensified antiretroviral therapy (ART) may be associated with cognitive benefits. METHODS: Therapy naïve, cognitively asymptomatic, HIV-positive individuals were randomly allocated on a 1:1 basis to standard ART (Arm1; tenofovir-emtricitabine plus atazanavir/ritonavir) or maraviroc intensified ART (Arm2: abacavir-lamivudine plus darunavir/ritonavir/maraviroc). Over 48 weeks, detailed assessments of cognitive function (CF) tests were undertaken and cerebral metabolites measured using proton magnetic resonance spectroscopy...
February 12, 2018: AIDS
Cleophas Chimbetete, David Katzenstein, Tinei Shamu, Adrian Spoerri, Janne Estill, Matthias Egger, Olivia Keiser
Objectives: To analyze the patterns and risk factors of HIV drug resistance mutations among patients failing second-line treatment and to describe early treatment responses to recommended third-line antiretroviral therapy (ART) in a national referral HIV clinic in Zimbabwe. Methods: Patients on boosted protease inhibitor (PI) regimens for more than 6 months with treatment failure confirmed by 2 viral load (VL) tests >1000 copies/mL were genotyped, and susceptibility to available antiretroviral drugs was estimated by the Stanford HIVdb program...
February 2018: Open Forum Infectious Diseases
Richard A Elion, Keri N Althoff, Jinbing Zhang, Richard D Moore, Stephen J Gange, Mari M Kitahata, Heidi M Crane, Daniel R Drozd, James H Stein, Marina B Klein, Joseph J Eron, Michael J Silverberg, William C Mathews, Amy C Justice, Timothy R Sterling, Charles S Rabkin, Angel M Mayor, Daniel B Klein, Michael A Horberg, Ronald J Bosch, Oghenowede Eyawo, Frank J Palella
BACKGROUND: There is persistent confusion as to whether abacavir (ABC) increases the risk for myocardial infarction (MI), and whether such risk differs by Type 1 (T1MI) or 2 (T2MI) MI in adults with HIV. METHODS: Incident MIs in NA-ACCORD participants were identified from 2001 to 2013. Discrete time marginal structural models addressed channeling biases and time-dependent confounding to estimate crude (HR) and adjusted hazard ratios (aHR) and 95% confidence intervals; analyses were performed for T1MI and T2MI separately...
February 6, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Marco Floridia, Carmela Pinnetti, Marina Ravizza, Giulia Masuelli, Carlo Personeni, Matilde Sansone, Anna Degli Antoni, Giovanni Guaraldi, Arsenio Spinillo, Beatrice Tassis, Serena Dalzero, Giuseppina Liuzzi, Enrica Tamburrini
BACKGROUND: Abacavir-lamivudine (ABC/3TC) and tenofovir-emtricitabine (TDF/FTC) represent in the guidelines of several countries, including Italy and United States, the preferred nucleoside/nucleotide backbones of antiretroviral regimens. We assessed their profile in pregnancy using data from a national observational study. METHODS: Laboratory measures (CD4, HIV-RNA, lipid profile, glucose, haemoglobin, ALT) and pregnancy outcomes (preterm delivery, low birthweight, nonelective cesarean section, birthweight Z-score, congenital defects, HIV transmission, maternal weight gain, pregnancy complications) were compared following prenatal exposure to ABC/3TC or TDF/FTC...
February 5, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
George Van Den Driessche, Denis Fourches
BACKGROUND: Idiosyncratic adverse drug reactions have been linked to a drug's ability to bind with a human leukocyte antigen (HLA) protein. However, due to the thousands of HLA variants and limited structural data for drug-HLA complexes, predicting a specific drug-HLA combination represents a significant challenge. Recently, we investigated the binding mode of abacavir with the HLA-B*57:01 variant using molecular docking. Herein, we developed a new ensemble screening workflow involving three X-ray crystal derived docking procedures to screen the DrugBank database and identify potentially HLA-B*57:01 liable drugs...
January 30, 2018: Journal of Cheminformatics
Renate Strehlau, Stephanie Shiau, Stephen Arpadi, Faeezah Patel, Francoise Pinillos, Wei-Yann Tsai, Ashraf Coovadia, Elaine Abrams, Louise Kuhn
Objectives. : Abacavir has replaced stavudine in antiretroviral therapy (ART) regimens because it has largely been phased out as a result of toxicity concerns; this loss has reduced further the already-limited drug options for children. Few data regarding virologic and metabolic outcomes among children who undergo substitution of stavudine exist. We evaluated the effects of preemptive substitution of abacavir for stavudine in children initially without lipodystrophy and virally suppressed on a stavudine-containing regimen...
January 24, 2018: Journal of the Pediatric Infectious Diseases Society
H B Krentz, S Campbell, V C Gill, M J Gill
OBJECTIVES: The incremental costs of expanding antiretroviral (ARV) drug treatment to all HIV-infected patients are substantial, so cost-saving initiatives are important. Our objectives were to determine the acceptability and financial impact of de-simplifying (i.e. switching) more expensive single-tablet formulations (STFs) to less expensive generic-based multi-tablet components. We determined physician and patient perceptions and acceptance of STF de-simplification within the context of a publicly funded ARV budget...
January 25, 2018: HIV Medicine
Chotirat Nakaranurack, Weerawat Manosuthi
OBJECTIVES: The prevalence of non-AIDS-related comorbidities is increasing in HIV-infected patients receiving antiretroviral therapy. In Thailand, data regarding the prevalence of non-AIDS comorbidities and factors associated with metabolic complications in HIV-infected patients have not been well-documented. METHODS: This cross-sectional study was conducted in 2011 and included 874 HIV-infected patients. RESULTS: The age of patients was 45(8) years represented as mean (standard deviation [SD])...
January 2018: Journal of the International Association of Providers of AIDS Care
Victor Collado-Diaz, Isabel Andujar, Ainhoa Sanchez-Lopez, Samuel Orden, María Amparo Blanch-Ruiz, María Angeles Martinez-Cuesta, Ana Blas-García, Juan V Esplugues, Ángeles Álvarez
Objective and methods: The effects of abacavir were evaluated in a validated model of arterial thrombosis. The role of ATP-P2X7-receptors and the actions of two vascular-damaging agents (diclofenac or rofecoxib) and other NRTIs were also analysed. Results: Abacavir dose-dependently promoted thrombus formation. This effect was reversed by a P2X7-receptor antagonist and was non-existent in P2X7 KO mice. The effects of abacavir were similar to those of diclofenac and rofecoxib...
January 16, 2018: Journal of Infectious Diseases
N Chantal Peltenburg, Jörgen Bierau, Jaap A Bakker, Jolanda A Schippers, Selwyn H Lowe, Aimée D C Paulussen, Bianca J C van den Bosch, Mathie P G Leers, Bettina E Hansen, Annelies Verbon
The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5'-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seropositive patients, AEs were defined as events that led to stop of cART regimen. ITPase activity ≥4 mmol IMP/mmol Hb/hour was considered as normal...
2018: PloS One
Binbin Song, Shigeki Aoki, Cong Liu, Takeshi Susukida, Kousei Ito
Genome-wide association studies indicate that several idiosyncratic adverse drug reactions are highly associated with specific human leukocyte antigen (HLA) alleles. For instance, abacavir, a human immunodeficiency virus reverse transcriptase inhibitor, induces multi-organ toxicity exclusively in patients carrying the HLA-B*57:01 allele. However, the underlying mechanism is unclear due to a lack of appropriate animal models. Previously, we developed HLA-B*57:01 transgenic mice and found that topical application of abacavir to the ears induced proliferation of CD8+ lymphocytes in local lymph nodes...
January 8, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
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
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