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Dolutegravir

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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/27893693/two-case-reports-of-severe-myocarditis-associated-with-the-initiation-of-dolutegravir-treatment-in-hiv-patients
#2
Keren Mahlab-Guri, Ilan Asher, Shira Rosenberg-Bezalel, Daniel Elbirt, Michael Burke, Zev M Sthoeger
RATIONALE: The integrase inhibitor dolutegravir is now recommended as first-line treatment for HIV. A single case of myocarditis after treatment with dolutegravir was reported in the FLAMINGO trial. We present here 2 cases of severe myocarditis that occurred shortly after the initiation of dolutegravir treatment. PATIENTS CONCERNS: The first case is a 45-year-old female who developed severe congestive heart failure and died, weeks after the initiation of dolutegravir treatment (for simplification of her antiretroviral regimen)...
November 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27882352/quantitative-evaluation-of-the-antiretroviral-efficacy-of-dolutegravir
#3
Sarah B Laskey, Robert F Siliciano
The second-generation HIV-1 integrase strand transfer inhibitor (InSTI) dolutegravir (DTG) has had a major impact on the treatment of HIV-1 infection. Here we describe important but previously undetermined pharmacodynamic parameters for DTG. We show that the dose-response curve slope, which indicates cooperativity and is a major determinant of antiviral activity, is higher for DTG than for first-generation InSTIs. This steepness does not reflect inhibition of multiple steps in the HIV-1 life cycle, as is the case for allosteric integrase inhibitors and HIV-1 protease inhibitors...
November 17, 2016: JCI Insight
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/27834772/early-neuropsychological-adverse-events-after-switching-from-pi-r-to-dolutegravir-could-be-related-to-hyperthyroidism-in-patients-under-levothyroxine
#6
Jean-Luc Berger, Yohan Nguyen, Delphine Lebrun, Caroline Migault, Maxime Hentzien, Hélène Marty, Firouzé Bani-Sadr
No abstract text is available yet for this article.
December 11, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27826447/experience-of-dolutegravir-in-hiv-infected-treatment-naive-patients-from-a-tertiary-care-university-hospital-in-ireland
#7
Sarmad Waqas, Mairead O'Connor, Ciara Levey, Paddy Mallon, Gerard Sheehan, Anjali Patel, Gordana Avramovic, John S Lambert
OBJECTIVE: Dolutegravir, an HIV integrase inhibitor, is a relatively new treatment option. To assess the tolerability, side effects, and time to viral decline to non-detectable in patients newly started on dolutegravir. METHODS: Retrospective health care record of 61 consecutive HIV treatment-naive patients started on dolutegravir was reviewed and analysed on SPSS. RESULTS: The mean initial viral load was 160826.05 copies/mL (range, 79-1,126,617 copies/mL)...
2016: SAGE Open Medicine
https://www.readbyqxmd.com/read/27824625/intolerance-of-dolutegravir-containing-combination-antiretroviral-therapy-regimens-in-real-life-clinical-practice
#8
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/27804313/antiretroviral-treatment-for-hiv-infection-swedish-recommendations-2016
#9
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/27799824/profile-of-cabotegravir-and-its-potential-in-the-treatment-and-prevention-of-hiv-1-infection-evidence-to-date
#10
REVIEW
Thomas Whitfield, Adele Torkington, Clare van Halsema
Modern antiretroviral therapy has demonstrated effectiveness in preexposure prophylaxis (PrEP) and treatment of HIV infection. There is a demand for prevention and treatment regimens that could overcome challenges of improving adherence, toxicity, and dosing convenience. Cabotegravir is an integrase strand transfer inhibitor and an analog of dolutegravir. Unlike dolutegravir, cabotegravir has a long half-life and can be formulated into a long-acting nanosuspension for parenteral administration. Initial pharmokinetic studies in humans have demonstrated adequate drug levels with intramuscular (IM) administration at 4 weekly and 8 weekly intervals, with few interactions with commonly used concomitant medications...
2016: HIV/AIDS: Research and Palliative Care
https://www.readbyqxmd.com/read/27798496/how-recent-findings-on-the-pharmacokinetics-and-pharmacodynamics-of-integrase-inhibitors-can-inform-clinical-use
#11
Emilie Elliot, Mimie Chirwa, Marta Boffito
PURPOSE OF REVIEW: This review of recent published literature and data presented at scientific meetings on integrase stand transfer inhibitors (InSTIs) examines how these findings may impact on their future clinical use. RECENT FINDINGS: Elvitegravir (EVG), raltegravir (RAL) and dolutegravir (DTG) are InSTIs recommended as first-line options for treatment naive patients by the European AIDS Clinical Society, British HIV Association, International AIDS Society-USA and DHHS...
October 27, 2016: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/27789848/dolutegravir-50%C3%A2-mg-thrice-weekly-plus-atazanavir-400%C3%A2-mg-daily-in-a-long-term-virologically-suppressed-hiv-infected-patient
#12
Massimiliano Lanzafame, Emanuela Lattuada, Stefano Nicolè, Fabio Rigo, Giulia Cucchetto, Ercole Concia, Sandro Vento
Highly active antiretroviral therapy (HAART) has changed the natural course of HIV infection. However, the toxicities associated with long-term use of nucleoside reverse transcriptase inhibitors (NRTIs) have led to the assessment of dual-therapy approaches with less toxicity. Atazanavir and dolutegravir have antiviral potency, tolerability and favourable metabolic profile. In suppressed HIV-infected patients, with NRTIs-related toxicity effects, the association of atazanavir and dolutegravir, favoured by their positive pharmacokinetics interaction, could be used as 'maintenance' antiretroviral therapy...
October 27, 2016: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/27782968/dolutegravir-in-breast-milk-and-maternal-and-infant-plasma-during-breastfeeding
#13
Robin Kobbe, Stein Schalkwijk, Gabor Dunay, Johanna M Eberhard, Ulf Schulze-Sturm, Bettina Hollwitz, Olaf Degen, Marga Teulen, Angela Colbers, David Burger
No abstract text is available yet for this article.
November 13, 2016: AIDS
https://www.readbyqxmd.com/read/27781100/how-can-we-achieve-universal-access-to-low-cost-treatment-for-hiv
#14
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/27741309/switch-to-dolutegravir-plus-rilpivirine-dual-therapy-in-cart-experienced-subjects-an-observational-cohort
#15
Amedeo F Capetti, Gaetana Sterrantino, Maria Vittoria Cossu, GianCarlo Orofino, Giorgio Barbarini, Giuseppe V De Socio, Simona Di Giambenedetto, Antonio Di Biagio, Benedetto M Celesia, Barbara Argenteri, Giuliano Rizzardini
INTRODUCTION: Little information is available on the efficacy and safety of the dual combination of ripivirine plus dolutegravir. This work aims at beginning to fill this gap. METHODS: All HIV-1 infected subjects treated with ripivirine plus dolutegravir between October 2014 and September 2015 in eight Italian centres were included in an observational cohort. Data were collected at baseline and at weeks 4, 12, 24 and 48. RESULTS: One hundred and thirty-two subjects were followed for a median of 24 months, mean 33 months...
2016: PloS One
https://www.readbyqxmd.com/read/27737783/development-of-a-phenotypic-susceptibility-assay-for-hiv-1-integrase-inhibitors
#16
Eva Heger, Alexandra Andrée Theis, Klaus Remmel, Hauke Walter, Alejandro Pironti, Elena Knops, Veronica Di Cristanziano, Björn Jensen, Stefan Esser, Rolf Kaiser, Nadine Lübke
Phenotypic resistance analysis is an indispensable method for determination of HIV-1 resistance and cross-resistance to novel drug compounds. Since integrase inhibitors are essential components of recent antiretroviral combination therapies, phenotypic resistance data, in conjunction with the corresponding genotypes, are needed for improving rules-based and data-driven tools for resistance prediction, such as HIV-Grade and geno2pheno[integrase]. For generation of phenotypic resistance data to recent integrase inhibitors, a recombinant phenotypic integrase susceptibility assay was established...
October 11, 2016: Journal of Virological Methods
https://www.readbyqxmd.com/read/27736953/projected-uptake-of-new-antiretroviral-arv-medicines-in-adults-in-low-and-middle-income-countries-a-forecast-analysis-2015-2025
#17
Aastha Gupta, Sandeep Juneja, Marco Vitoria, Vincent Habiyambere, Boniface Dongmo Nguimfack, Meg Doherty, Daniel Low-Beer
With anti-retroviral treatment (ART) scale-up set to continue over the next few years it is of key importance that manufacturers and planners in low- and middle-income countries (LMICs) hardest hit by the HIV/AIDS pandemic are able to anticipate and respond to future changes to treatment regimens, generics pipeline and demand, in order to secure continued access to all ARV medicines required. We did a forecast analysis, using secondary WHO and UNAIDS data sources, to estimate the number of people living with HIV (PLHIV) and the market share and demand for a range of new and existing ARV drugs in LMICs up to 2025...
2016: PloS One
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
#18
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/27714978/switching-regimens-in-virologically-suppressed-hiv-1-infected-patients-evidence-base-and-rationale-for-integrase-strand-transfer-inhibitor-insti-containing-regimens
#19
REVIEW
F Raffi, S Esser, G Nunnari, I Pérez-Valero, L Waters
In an era when most individuals with treated HIV infection can expect to live into old age, clinicians should proactively review their patients' current and future treatment needs and challenges. Clinical guidelines acknowledge that, in the setting of virological suppression, treatment switch may yield benefits in terms of tolerability, regimen simplification, adherence, convenience and long-term health considerations, particularly in the context of ageing. In this paper, we review evidence from six key clinical studies on switching virologically suppressed patients to regimens based on integrase strand transfer inhibitors (INSTIs), the antiretroviral class increasingly preferred as initial therapy in clinical guidelines...
October 2016: HIV Medicine
https://www.readbyqxmd.com/read/27699622/a-two-way-steady-state-pharmacokinetic-interaction-study-of-doravirine-mk-1439-and-dolutegravir
#20
Matt S Anderson, Sauzanne Khalilieh, Ka Lai Yee, Rachael Liu, Li Fan, Matthew L Rizk, Vedangi Shah, Azra Hussaini, Ivy Song, Lisa L Ross, Joan R Butterton
INTRODUCTION: Doravirine, a non-nucleoside reverse-transcriptase inhibitor in development for the treatment of patients with human immunodeficiency virus-1 infection, has potential to be used concomitantly in antiretroviral therapy with dolutegravir, an integrase strand transfer inhibitor. The pharmacokinetic interactions between these drugs were therefore assessed. METHODS: Oral formulations of doravirine and dolutegravir were dosed both individually and concomitantly once daily in healthy adults...
October 4, 2016: Clinical Pharmacokinetics
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