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https://www.readbyqxmd.com/read/28333231/tolerability-of-integrase-inhibitors-in-a-real-life-setting
#1
Judit Peñafiel, Elisa de Lazzari, Mireia Padilla, Jhon Rojas, Ana Gonzalez-Cordon, Jose L Blanco, Jordi Blanch, Maria A Marcos, Montserrat Lonca, Maria Martinez-Rebollar, Montserrat Laguno, Amparo Tricas, Ana Rodriguez, Josep Mallolas, Jose M Gatell, Esteban Martinez
Background: Integrase inhibitors have shown better tolerability than other drugs in clinical trials, but some post-marketing data have suggested potential differences among them. Aims: We compared rates and reasons for discontinuation of raltegravir-, elvitegravir- and dolutegravir-based regimens in a large cohort of HIV-infected patients. Methods: Retrospective analysis of a prospectively followed cohort including all antiretroviral-naive and all virologically suppressed antiretroviral-experienced patients prescribed a first regimen containing raltegravir, elvitegravir or dolutegravir with at least one follow-up visit...
February 28, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28330477/inhibition-of-human-endogenous-retrovirus-k-by-antiretroviral-drugs
#2
Richa Tyagi, Wenxue Li, Danelvis Parades, Mario A Bianchet, Avindra Nath
BACKGROUND: Human endogenous retroviruses (HERVs) are genomic sequences of retroviral origin which were believed to be integrated into germline chromosomes millions of years ago and account for nearly 8% of the human genome. Although mostly defective and inactive, some of the HERVs may be activated under certain physiological and pathological conditions. While no drugs are designed specifically targeting HERVs, there are a panel of antiretroviral drugs designed against the human immunodeficiency virus and approved by the Federal Drug Administration (FDA)...
March 22, 2017: Retrovirology
https://www.readbyqxmd.com/read/28285916/discovery-and-optimization-of-2-pyridinone-aminal-integrase-strand-transfer-inhibitors-for-the-treatment-of-hiv
#3
John D Schreier, Mark W Embrey, Izzat T Raheem, Guillaume Barbe, Louis-Charles Campeau, David Dubost, Jamie McCabe Dunn, Jay Grobler, Timothy J Hartingh, Daria J Hazuda, Daniel Klein, Michael D Miller, Keith P Moore, Natalie Nguyen, Natasa Pajkovic, David A Powell, Vanessa Rada, John M Sanders, John Sisko, Thomas G Steele, John Wai, Abbas Walji, Min Xu, Paul J Coleman
HIV integrase strand transfer inhibitors (InSTIs) represent an important class of antiviral therapeutics with proven efficacy and excellent tolerability for the treatment of HIV infections. In 2007, Raltegravir became the first marketed strand transfer inhibitor pioneering the way to a first-line therapy for treatment-naïve patients. Challenges with this class of therapeutics remain, including frequency of the dosing regimen and the genetic barrier to resistance. To address these issues, research towards next-generation integrase inhibitors has focused on imparting potency against RAL-resistent mutants and improving pharmacokinetic profiles...
February 20, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28263457/ombitasvir-paritaprevir-ritonavir-and-dasabuvir-drug-interactions-with-antiretroviral-agents-and-drugs-forsubstance-abuse
#4
Jennifer R King, Rajeev M Menon
AbbVie's 3 direct-acting antiviral (3D) regimen containing ombitasvir, paritaprevir, ritonavir, and dasabuvir with and without ribavirin is approved for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection. Safe and efficacious antiviral regimens resulting in minimal to no drug-drug interactions (DDIs) with antiretrovirals are needed to ensure that patients coinfected with HCV and the human immunodeficiency virus (HIV) achieve 12-week sustained virologic response rates similar to HCV-monoinfected patients...
March 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28225830/ex-vivo-activation-of-cd4-t-cells-from-donors-on-suppressive-art-can-lead-to-sustained-production-of-infectious-hiv-1-from-a-subset-of-infected-cells
#5
John K Bui, Elias K Halvas, Elizabeth Fyne, Michele D Sobolewski, Dianna Koontz, Wei Shao, Brian Luke, Feiyu F Hong, Mary F Kearney, John W Mellors
The fate of HIV-infected cells after reversal of proviral latency is not well characterized. Simonetti, et al. recently showed that CD4+ T-cells containing intact proviruses can clonally expand in vivo and produce low-level infectious viremia. We hypothesized that reversal of HIV latency by activation of CD4+ T-cells can lead to the expansion of a subset of virus-producing cells rather than their elimination. We established an ex vivo cell culture system involving stimulation of CD4+ T-cells from donors on suppressive antiretroviral therapy (ART) with PMA/ionomycin (day 1-7), followed by rest (day 7-21), and then repeat stimulation (day 21-28), always in the presence of high concentrations of raltegravir and efavirenz to effectively block new cycles of viral replication...
February 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28212411/lack-of-impact-of-pre-existing-t97a-hiv-1-integrase-mutation-on-integrase-strand-transfer-inhibitor-resistance-and-treatment-outcome
#6
Michael E Abram, Renee R Ram, Nicolas A Margot, Tiffany L Barnes, Kirsten L White, Christian Callebaut, Michael D Miller
T97A is an HIV-1 integrase polymorphism associated with integrase strand transfer inhibitor (INSTI) resistance. Using pooled data from 16 clinical studies, we investigated the prevalence of T97A (pre-existing and emergent) and its impact on INSTI susceptibility and treatment response in INSTI-naive patients who enrolled on elvitegravir (EVG)- or raltegravir (RAL)-based regimens. Prior to INSTI-based therapy, primary INSTI resistance-associated mutations (RAMs) were absent and T97A pre-existed infrequently (1...
2017: PloS One
https://www.readbyqxmd.com/read/28207816/hiv-drug-therapy-duration-a-swedish-real-world-nationwide-cohort-study-on-infcarehiv-2009-2014
#7
Amanda Häggblom, Stefan Lindbäck, Magnus Gisslén, Leo Flamholc, Bo Hejdeman, Andreas Palmborg, Amy Leval, Eva Herweijer, Sverrir Valgardsson, Veronica Svedhem
BACKGROUND: As HIV infection needs a lifelong treatment, studying drug therapy duration and factors influencing treatment durability is crucial. The Swedish database InfCareHIV includes high quality data from more than 99% of all patients diagnosed with HIV infection in Sweden and provides a unique opportunity to examine outcomes in a nationwide real world cohort. METHODS: Adult patients who started a new therapy defined as a new 3rd agent (all antiretrovirals that are not N[t]RTIs) 2009-2014 with more than 100 observations in treatment-naive or treatment-experienced patients were included...
2017: PloS One
https://www.readbyqxmd.com/read/28198351/therapeutic-drug-monitoring-guided-raltegravir-dosing-for-prevention-of-vertical-transmission-in-a-premature-neonate-born-to-a-woman-living-with-perinatally-acquired-hiv
#8
Denise Kreutzwiser, Nancy Sheehan, Natalie Dayneka, Benoît Lemire, Alison Wong, Lindy Samson, Jason Brophy
We report a case of therapeutic drug monitoring guided raltegravir use for the prevention of vertical HIV transmission in a premature neonate born to a woman living with perinatally acquired HIV and documented resistance to multiple HIV drugs. Maternal viral load was above 1,000 copies/mL at delivery. This case demonstrates delayed raltegravir elimination in a neonate born at 33 weeks gestational age and a need for less frequent raltegravir dosing than is used in older infants and children.
February 15, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28134057/hiv-viral-kinetics-and-t-cell-dynamics-in-antiretroviral-na%C3%A3-ve-persons-starting-an-integrase-strand-transfer-inhibitor-and-protease-inhibitor-regimen
#9
Maile Y Karris, Sonia Jain, Tyler R C Day, Josué Pérez-Santiago, Miguel Goicoechea, Michael P Dubé, Xiaoying Sun, Celsa Spina, Eric S Daar, Richard H Haubrich, Sheldon Morris
BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens may potentially minimize antiretroviral (ART) toxicities, but demonstrate mixed efficacy and toxicity results. The impact of an integrase strand transfer inhibitor (INSTI) and protease inhibitor (PI) regimen on HIV viral dynamics and T cell kinetics remains underdescribed. OBJECTIVE: To compare the effect of raltegravir + ritonavir boosted lopinavir (RAL + LPV/r) to efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) on HIV kinetics and T cell dynamics...
March 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28125951/quality-of-life-improvement-in-hiv-1-patients-treated-with-raltegravir-in-a-real-life-observational-study-racing
#10
Bruno Spire, Lella Nait-Ighil, Pascal Pugliese, Isabelle Poizot-Martin, Vincent Jullien, Anne-Geneviève Marcelin, Eric Billaud
BACKGROUND: Good efficacy and safety of raltegravir in person living with HIV was demonstrated in clinical trials over five years, but real-life data, particularly about quality of life (QoL), are lacking. QoL was evaluated over time in adult patients first treated or switched to regimens containing raltegravir in an observational cohort study. METHODS: Patient QoL was evaluated using the Fatigue Impact Scale (FIS) and the HIV Symptom Index (HSI). Data were collected at baseline and at 1, 3, 6, 12, 18, and 24 months...
January 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28124232/effectiveness-and-risk-factors-for-virological-outcome-of-raltegravir-based-therapy-for-treatment-experienced-hiv-infected-patients
#11
José Antonio Mata-Marín, Ariane Estrella Weiser Smeke, Mariana Rotzinger Rodriguez, Marcelino Chávez-García, Marco Isaac Banda-Lara, Alma Minerva Pérez Rios, Nohemí Nuñez-Rodríguez, Juan Carlos Domínguez-Hermosillo, Alberto Chaparro Sánchez, Irene Juarez-Kasusky, Javier Enrique Cruz Herrera, Jorge Luis Sandoval Ramírez, Jesús Gaytán-Martínez
OBJECTIVE: We evaluated the effectiveness of a raltegravir (RAL)-containing regimen plus an optimized background regimen in HIV-1 highly treatment-experienced patients. DESIGN: A retrospective cohort, multicentre study was conducted. METHODS: Adult (>16 years old) HIV treatment-experience patients starting therapy with a RAL-containing regimen were included. Effectiveness was evaluated as the percentage of patients with an undetectable HIV-1 RNA viral load (<50 and <200 copies/mL) after 48 weeks, and changes in CD4+ cell counts...
March 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28116848/plasma-trough-concentrations-of-darunavir-ritonavir-and-raltegravir-in-older-patients-with-hiv-1-infection
#12
L Calza, V Colangeli, E Magistrelli, L Bussini, M Conti, E Ramazzotti, R Mancini, P Viale
OBJECTIVES: The aim of the study was to assess plasma concentrations of darunavir/ritonavir and raltegravir in older patients compared with younger patients with HIV-1 infection. METHODS: In this observational, open-label study, adult HIV-infected out-patients aged ≤ 40 years (younger patients) or ≥ 60 years (older patients) and treated with tenofovir/emtricitabine plus darunavir/ritonavir (800/100 mg daily) or raltegravir (400 mg twice daily) were asked to participate...
January 24, 2017: HIV Medicine
https://www.readbyqxmd.com/read/28088884/dual-raltegravir-etravirine-combination-as-maintenance-regimen-in-virologically-suppressed-hiv-1-infected-patients
#13
Leonardo Calza, Eleonora Magistrelli, Vincenzo Colangeli, Roberto Manfredi, Marco Borderi, Nicolò Rossi, Matteo Conti, Rita Mancini, Pierluigi Viale
BACKGROUND: Nucleoside reverse transcriptase inhibitor (NRTI)- and protease inhibitor (PI)-sparing antiretroviral regimens may be useful in selected HIV-infected patients with resistance or intolerance to these drug classes. METHODS: This was an observational prospective study of patients on suppressive antiretroviral therapy containing two NRTIs plus one ritonavir-boosted PI who switched to a dual regimen containing raltegravir plus etravirine. Patients were required not to have prior virological failure to raltegravir and to have efficacy of etravirine showed through the genotypic resistance assay in case of prior non-nucleoside reverse transcriptase inhibitor (NNRTI) virological failure...
January 15, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28086908/hiv-integration-sites-in-latently-infected-cell-lines-evidence-of-ongoing-replication
#14
Jori Symons, Abha Chopra, Eva Malantinkova, Ward De Spiegelaere, Shay Leary, Don Cooper, Chike O Abana, Ajantha Rhodes, Simin D Rezaei, Linos Vandekerckhove, Simon Mallal, Sharon R Lewin, Paul U Cameron
BACKGROUND: Assessing the location and frequency of HIV integration sites in latently infected cells can potentially inform our understanding of how HIV persists during combination antiretroviral therapy. We developed a novel high throughput sequencing method to evaluate HIV integration sites in latently infected cell lines to determine whether there was virus replication or clonal expansion in these cell lines observed as multiple integration events at the same position. RESULTS: We modified a previously reported method using random DNA shearing and PCR to allow for high throughput robotic processing to identify the site and frequency of HIV integration in latently infected cell lines...
January 13, 2017: Retrovirology
https://www.readbyqxmd.com/read/28073704/raltegravir-induced-drug-reaction-with-eosinophilia-and-systemic-symptoms-syndrome-in-a-child
#15
Felicia A Scaggs, Mariam S Aziz, Erica L Palmisano, Mahboobeh Mahdavinia, Sheela S Raikar, Latania K Logan
No abstract text is available yet for this article.
December 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/28065890/impact-of-obesity-on-antiretroviral-pharmacokinetics-and-immuno-virological-response-in-hiv-infected-patients-a-case-control-study
#16
Vincent Madelain, Minh P Le, Karen Champenois, Charlotte Charpentier, Roland Landman, Veronique Joly, Patrick Yeni, Diane Descamps, Yazdan Yazdanpanah, Gilles Peytavin
BACKGROUND: Obesity has high prevalence among HIV-infected patients. Increased adipose tissue mass affects the pharmacokinetics of numerous drugs, but few data are available for antiretroviral drugs. OBJECTIVES: In this study we aimed to explore the pharmacokinetics of antiretroviral drugs and the immuno-virological response in obese patients with HIV infection. PATIENTS AND METHODS: We examined data from 2009 to 2012 in our hospital's database for HIV-1-infected patients who received an antiretroviral drug (abacavir, emtricitabine, lamivudine, tenofovir, efavirenz, etravirine, nevirapine, atazanavir/ritonavir, darunavir/ritonavir, lopinavir/ritonavir or raltegravir)...
January 8, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28051809/pregnancy-related-changes-of-antiretroviral-pharmacokinetics-an-argument-for-tdm
#17
Francesco R Simonetti, Dario Cattaneo, Nadia Zanchetta, Vania Giacomet, Valeria Micheli, Nadia Ciminera, Cristina Gervasoni
Here we describe a case of an HIV-infected young woman with extensive drug-resistant virus, who was successfully switched from a raltegravir-based regimen to a dolutegravir-based intensified antiretroviral regimen a few days before scheduled caesarean section because of the still detectable viral load. The trough concentrations of all antiretroviral drugs before and after delivery are also described.Our case underlines both the difficult management of young women, HIV-infected at young age with very limited treatment options and the great variability in the pregnancy-related physiologic changes affecting the pharmacokinetics of antiretrovirals...
January 4, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28025011/influence-of-raltegravir-intensification-on-viral-load-and-2-ltr-dynamics-in-hiv-patients-on-suppressive-antiretroviral-therapy
#18
Xia Wang, Gregory Mink, Daniel Lin, Xinyu Song, Libin Rong
Antiretroviral therapy can suppress HIV-1 plasma viral load to below the detection limit but cannot eradicate the virus. Whether residual ongoing viral replication persists during suppressive therapy remains unclear. A few clinical studies showed that treatment intensification with an additional drug led to a lower viral load or an increase in 2-LTR (long terminal repeat), a marker for ongoing viral replication. However, some other studies found no change in the viral load and 2-LTR. In this paper, we developed multi-stage models to evaluate the influence of treatment intensification with the integrase inhibitor raltegravir on viral load and 2-LTR dynamics in HIV patients under suppressive therapy...
December 23, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28010138/synthesis-molecular-modeling-and-biological-evaluation-of-two-new-chicoric-acid-analogs
#19
Giuliana Righi, Romina Pelagalli, Valerio Isoni, Ilaria Tirotta, Roberto Dallocchio, Alessandro Dessì, Beatrice Macchi, Caterina Frezza, Ilaria Rossetti, Paolo Bovicelli
Two conformationally constrained compounds similar to chicoric acid but lacking the catechol and carboxyl groups were prepared. In these analogues, the single bond between the two caffeoyl fragments has been replaced with a chiral oxirane ring and both aromatic residues modified protecting completely or partially the catechol moiety as methyl ether. Preliminary molecular modelling studies carried out on the two analogues showed interactions near the active site of HIV integrase; however, in comparison with raltegravir, the biological evaluation confirmed that CAA-1 and CAA-2 were unable to inhibit infection at lower concentration...
February 2017: Natural Product Research
https://www.readbyqxmd.com/read/27999055/unravelling-the-dynamics-of-selection-of-multiresistant-variants-to-integrase-inhibitors-in-an-hiv-1-infected-child-using-ultra-deep-sequencing
#20
Karl Stefic, Maud Salmona, Marisa Capitao, Marion Splittgerber, Zoha Maakaroun-Vermesse, Marie-Laure Néré, Louis Bernard, Marie-Laure Chaix, Francis Barin, Constance Delaugerre
BACKGROUND: Ultra-deep sequencing (UDS) allows detection of minority resistant variants (MRVs) with a threshold of 1% and could be useful to identify variants harbouring single or multiple drug-resistance mutations (DRMs). OBJECTIVES: We analysed the integrase gene region longitudinally using UDS in an HIV-1-infected child rapidly failing a raltegravir-based regimen. METHODS: Longitudinal plasma samples at baseline and weeks 4, 8, 13, 17 and 39 were obtained, as well as the mother's baseline plasma sample...
December 20, 2016: Journal of Antimicrobial Chemotherapy
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