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Dolutegravir

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https://www.readbyqxmd.com/read/29469716/associated-conditions-in-patients-with-multiple-dermatofibromas-case-reports-and-literature-review
#1
Surget V Beatrous, Ryan R Riahi, Stratton B Grisoli, Philip R Cohen
Dermatofibromas are benign, fibrohistiocytic, dermal tumors. Solitary dermatofibromas may be incidental findings, whereas multiple dermatofibromas may be associated with systemic conditions or previous therapies. Two women and one man with multiple dermatofibromas and an associated systemic condition, immunosuppression, or both, are described. Nine dermatofibromas developed in a woman with hypothyroidism, optic neuritis, and Arnold Chiari I malformation. Five dermatofibromas developed in a woman with breast cancer who had received several systemic antineoplastic therapies...
September 22, 2017: Dermatology Online Journal
https://www.readbyqxmd.com/read/29444582/dolutegravir-based-regimens-are-active-in-integrase-strand-transfer-inhibitor-naive-patients-with-nucleoside-reverse-transcriptase-inhibitor-resistance
#2
James Demarest, Mark Underwood, Marty St Clair, David Dorey, Dannae Brown, Andrew Zolopa
Dolutegravir demonstrated superior virologic efficacy compared with raltegravir in treatment-experienced, integrase strand transfer inhibitor (INSTI)-naive patients with HIV-1 who harbored resistance to ≥2 classes of antiretroviral drugs. Significantly fewer dolutegravir-treated patients demonstrated virologic failure with treatment emergent resistance than raltegravir-treated patients through 48 weeks. Resistance analyses informed the design of investigator-selected background therapy (ISBT) that included at least 1 fully active agent...
February 14, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29442543/dolutegravir-dual-therapy-as-maintenance-treatment-in-hiv-infected-patients-a-review
#3
Rosaleen Boswell, Michelle M Foisy, Christine A Hughes
OBJECTIVE: To review available evidence for dolutegravir-based dual therapy as maintenance treatment in HIV-1 infected patients. DATA SOURCES: A literature search was conducted using PubMed, MEDLINE, and Google Scholar to the end of January 2018. Conference abstracts and article bibliographies were also reviewed. STUDY SELECTION AND DATA EXTRACTION: All English-language, randomized, and observational studies were included. DATA SYNTHESIS: In all, 12 studies were identified: 10 were observational, and 2 were randomized trials...
February 1, 2018: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/29435471/hiv-1-drug-resistance-and-third-line-therapy-outcomes-in-patients-failing-second-line-therapy-in-zimbabwe
#4
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
https://www.readbyqxmd.com/read/29424784/adverse-drug-reactions-to-integrase-strand-transfer-inhibitors
#5
Katherine J Lepik, Benita Yip, Ana Ulloa, Lu Wang, Junine Toy, Linda Akagi, Viviane Dias Lima, Silvia Guillemi, Julio S G Montaner, Rolando Barrios
OBJECTIVES: Describe and compare integrase strand transfer inhibitor (INSTI) adverse drug reactions (ADRs) for raltegravir, elvitegravir-cobicistat and dolutegravir. DESIGN: Population-based, retrospective cohort. METHODS: Antiretroviral-experienced and naive persons ≥19 years were included if they received their first prescription for raltegravir, elvitegravir-cobicistat or dolutegravir in British Columbia, Canada in 2012-2014, and were followed for two years until 31-Dec-2016...
February 8, 2018: AIDS
https://www.readbyqxmd.com/read/29424775/distribution-and-reduction-magnitude-of-hiv-dna-burden-in-cd4-t-cell-subsets-depend-on-art-initiation-timing
#6
Pierre Gantner, Cindy Barnig, Marialuisa Partisani, Guinevere Q Lee, Geneviève Beck-Wirth, Jean-Pierre Faller, Martin Martinot, Mahsa Mosheni-Zadeh, Christine Cheneau, Marie-Laure Batard, Patricia Fischer, Anne Fuchs, Béatrice Uring-Lambert, Siamak Bahram, David Rey, Samira Fafi-Kremer
OBJECTIVE: The aim of our study was to analyze the dynamics of HIV-DNA levels in CD4 T-cell subsets in individuals starting successful dolutegravir-based regimens. DESIGN: Twenty-seven individuals with acute infection (AI, n = 8) or chronic infection (CI, n = 5) and patients in virological success (VS, n = 10) or virological failure (VF, n = 4) on antiretroviral therapy (ART) who initiated a dolutegravir-based regimen were enrolled (NCT02557997)...
February 8, 2018: AIDS
https://www.readbyqxmd.com/read/29415844/a-potential-drug-interaction-between-phenobarbital-and-dolutegravir-a-case-report
#7
Shinichi Hikasa, Akihiro Sawada, Hitomi Seino, Shota Shimabukuro, Kyoko Hideta, Noriko Uwa, Satoshi Higasa, Tazuko Tokugawa, Takeshi Kimura
In this report, we describe a human immunodeficiency virus (HIV)-infected patient in whom changes in phenobarbital (PB) dosage resulted in associated changes in plasma concentrations of dolutegravir (DTG). His plasma concentrations of DTG were 0.934, 0.584, 1.003 and 3.25 μg/mL, respectively, with concomitant daily PB doses of 40, 70, 30 and 0 mg, respectively. This case suggests that PB can lead to a remarkable reduction in the plasma concentration of DTG in a dose-dependent manner.
February 4, 2018: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/29415190/cytokine-mediated-systemic-adverse-drug-reactions-in-a-drug-drug-interaction-study-of-dolutegravir-with-once-weekly-isoniazid-and-rifapentine
#8
Kristina M Brooks, Jomy M George, Alice K Pau, Adam Rupert, Carolina Mehaffy, Prithwiraj De, Karen M Dobos, Anela Kellogg, Mary McLaughlin, Maryellen McManus, Raul M Alfaro, Colleen Hadigan, Joseph A Kovacs, Parag Kumar
Background: Once-weekly isoniazid and rifapentine for 3 months is a treatment option in persons with human immunodeficiency virus and latent tuberculosis infection. This study aimed to examine pharmacokinetic drug-drug interactions between this regimen and dolutegravir, a first-line antiretroviral medication. Methods: This was a single-center, open-label, fixed-sequence, drug-drug interaction study in healthy volunteers. Subjects received oral dolutegravir 50 mg once-daily alone (Days 1-4) and concomitantly with once-weekly isoniazid 900 mg, rifapentine 900 mg, and pyridoxine 50 mg (Days 5-19)...
February 3, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29410019/novel-secondary-mutations-c56s-and-g149a-confer-resistance-to-hiv-1-integrase-strand-transfer-inhibitors
#9
Tomokazu Yoshinaga, Takahiro Seki, Shigeru Miki, Tadashi Miyamoto, Akemi Suyama-Kagitani, Shinobu Kawauchi-Miki, Masanori Kobayashi, Akihiko Sato, Eugene Stewart, Mark Underwood, Tamio Fujiwara
Cabotegravir (CAB, S/GSK1265744) is an investigational second-generation integrase strand transfer inhibitor (INSTI) with a chemical structure similar to dolutegravir. CAB is under development as a long-acting injectable formulation for treatment of HIV-1 infection and for pre-exposure prophylaxis. We conducted an in vitro passage study of raltegravir- or elvitegravir-resistant signature mutants in the presence of CAB to characterize the resistance profile of this drug. During passage with Q148H virus, G140S arose by day 14, followed by G149A and C56S...
January 30, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29402886/creation-of-a-long-acting-nanoformulated-dolutegravir
#10
Brady Sillman, Aditya N Bade, Prasanta K Dash, Biju Bhargavan, Ted Kocher, Saumi Mathews, Hang Su, Georgette D Kanmogne, Larisa Y Poluektova, Santhi Gorantla, JoEllyn McMillan, Nagsen Gautam, Yazen Alnouti, Benson Edagwa, Howard E Gendelman
Potent antiretroviral activities and a barrier to viral resistance characterize the human immunodeficiency virus type one (HIV-1) integrase strand transfer inhibitor dolutegravir (DTG). Herein, a long-acting parenteral DTG was created through chemical modification to improve treatment outcomes. A hydrophobic and lipophilic modified DTG prodrug is encapsulated into poloxamer nanoformulations (NMDTG) and characterized by size, shape, polydispersity, and stability. Retained intracytoplasmic NMDTG particles release drug from macrophages and attenuate viral replication and spread of virus to CD4+ T cells...
February 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29396773/dolutegravir-in-pregnancy-effects-on-hiv-positive-women-and-their-infants
#11
Riikka Bornhede, Sandra Soeria-Atmadja, Katarina Westling, Karin Pettersson, Lars Navér
The development of new drugs for treatment of HIV has increased the efficacy and the quality of life together with decreased unwanted side-effect for people living with HIV. The integrase inhibitor dolutegravir has in short time become part of the first-line treatment in many countries, but is not a recommended first-line drug in pregnancy. As there are few publications of dolutegravir use during pregnancy, we found it valuable to analyze the Stockholm pregnancy cohort. A retrospective analysis of all pregnant women and their infants exposed to dolutegravir at Karolinska University Hospital, 2014-August 2017...
February 2, 2018: European Journal of Clinical Microbiology & Infectious Diseases
https://www.readbyqxmd.com/read/29381562/dolutegravir-and-metformin-a-clinically-relevant-or-just-a-pharmacokinetic-interaction
#12
Dario Cattaneo, Chiara Resnati, Giuliano Rizzardini, Cristina Gervasoni
No abstract text is available yet for this article.
February 20, 2018: AIDS
https://www.readbyqxmd.com/read/29373677/pathway-involving-the-n155h-mutation-in-hiv-1-integrase-leads-to-dolutegravir-resistance
#13
Isabelle Malet, Francesca A Ambrosio, Frédéric Subra, Béatrice Herrmann, Hervé Leh, Marie-Christine Bouger, Anna Artese, Christine Katlama, Carmine Talarico, Isabella Romeo, Stefano Alcaro, Giosuè Costa, Eric Deprez, Vincent Calvez, Anne-Geneviève Marcelin, Olivier Delelis
Background: Dolutegravir, an integrase strand-transfer inhibitor (STI), shows a high genetic barrier to resistance. Dolutegravir is reported to be effective against viruses resistant to raltegravir and elvitegravir. In this study, we report the case of a patient treated with dolutegravir monotherapy. Failure of dolutegravir treatment was observed concomitant with the appearance of N155H-K211R-E212T mutations in the integrase (IN) gene in addition to the polymorphic K156N mutation that was present at baseline in this patient...
January 24, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29371105/effect-of-dolutegravir-in-combination-with-nucleoside-reverse-transcriptase-inhibitors-on-people-living-with-hiv-who-have-pre-existing-nucleoside-reverse-transcriptase-inhibitor-mutations
#14
Erik Sörstedt, Christina Carlander, Leo Flamholc, Bo Hejdeman, Veronica Svedhem, Anders Sönnerborg, Magnus Gisslén, Aylin Yilmaz
BACKGROUND: Until the introduction of dolutegravir (DTG), people living with HIV who have developed nucleoside reverse transcriptase inhibitor (NRTI) mutations have had few other treatment options outside of regimens based on ritonavir-boosted protease inhibitors (PI/r). Here we report treatment results among people living with HIV in Sweden with pre-existing NRTI mutations on antiretroviral treatment (ART) with DTG and 1-2 NRTIs. METHODS: All people living with HIV on ART with DTG and 1-2 NRTIs with pre-existing NRTI mutations were retrospectively identified from the national InfCare HIV database...
January 22, 2018: International Journal of Antimicrobial Agents
https://www.readbyqxmd.com/read/29369162/dolutegravir-pharmacokinetics-in-pregnant-and-postpartum-women-living-with-hiv
#15
Nikki Mulligan, Brookie M Best, Jiajia Wang, Edmund V Capparelli, Alice Stek, Emily Barr, Shelley L Buschur, Edward P Acosta, Elizabeth Smith, Nahida Chakhtoura, Sandra Burchett, Mark Mirochnick
OBJECTIVE: To evaluate dolutegravir pharmacokinetics during pregnancy compared to postpartum and in infant washout samples after delivery. DESIGN: Ongoing, nonrandomized, open-label, parallel-group, multicenter phase-IV prospective study of antiretroviral pharmacokinetics in HIV-infected pregnant women and infants. METHODS: Intensive steady-state 24 h pharmacokinetic profiles after dolutegravir 50 mg once-daily were performed during the second trimester (2T), third trimester (3T) and postpartum (PP)...
January 23, 2018: AIDS
https://www.readbyqxmd.com/read/29368401/patient-perspectives-on-de-simplifying-their-single-tablet-co-formulated-antiretroviral-therapy-for-societal-cost-savings
#16
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
https://www.readbyqxmd.com/read/29353487/absence-of-hiv-1-drug-resistance-mutations-supports-the-use-of-dolutegravir-in-uganda
#17
Emmanuel Ndashimye, Mariano Avino, Fred Kyeyune, Immaculate Nankya, Richard M Gibson, Eva Nabulime, Art F Y Poon, Cissy Kityo, Peter Mugyenyi, Miguel E Quinones-Mateu, Eric Arts
OBJECTIVES: To screen for drug resistance and possible treatment with Dolutegravir (DTG) in treatment naïve patients and those experiencing virologic failure during first, second, and third line combined antiretroviral therapy (cART) in Uganda. DESIGN: Samples from 417 patients in Uganda were analyzed for predicted drug resistance upon failing a first (N=158), second (N=121), or third line (all 51 involving Raltegravir [RAL]) treatment regimen. METHOD: HIV-1 pol gene was amplified and sequenced from plasma samples...
January 21, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29352755/a-mos1-transposase-in-vivo-assay-to-screen-new-hiv-1-integrase-inhibitors
#18
Mariana Cancian, Elgion L S Loreto
The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase. Using a Drosophila strain in which the mobilisation of the mariner element can be quantified by mosaic eyes, we showed that flies maintained in medium containing 210 µM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1 integrase inhibitor used in AIDS treatment, have 23-33% less somatic mobilisation in mosaic eyes when treated with raltegravir and 28-32% when treated with dolutegravir...
January 19, 2018: Genetica
https://www.readbyqxmd.com/read/29350111/sustained-viral-suppression-with-co-administration-of-oxcarbazepine-and-dolutegravir
#19
Manar M Kandil, Melissa E Badowski, Christopher A Schriever
Co-administration of dolutegravir and oxcarbazepine has been reported to reduce levels of dolutegravir and therefore is contraindicated due to insufficient data to make dosing recommendations. We present eight cases in which patients with human immunodeficiency virus (HIV) inadvertently received oxcarbazepine while concurrently receiving 50 mg of dolutegravir daily as part of their antiretroviral therapy. Upon further evaluation, lab results revealed that despite the risk of decreased levels of dolutegravir due to possible oxcarbazepine enzyme induction, patients maintained at or near virologic suppression (viral load <20 copies/ml)...
January 1, 2018: International Journal of STD & AIDS
https://www.readbyqxmd.com/read/29346270/resistance-to-hiv-integrase-inhibitors-about-r263k-and-e157q-mutations
#20
REVIEW
Charlotte Charpentier, Diane Descamps
The use of integrase inhibitors (INI) is increasing in antiretroviral therapies (ART) and INI are not all equal regarding genetic barrier to resistance. The aim of this manuscript was to review main in vivo and in vitro knowledge about two particular integrase resistance-associated mutations: R263K and E157Q. The R263K mutation was the first mutation rarely found selected at time of virological failure in patients failing a first-line dolutegravir-based treatment. Further in vitro studies on R263K mutants showed a moderate increase in phenotypic resistance level and a drastic reduction in viral replicative capacity...
January 18, 2018: Viruses
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