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https://www.readbyqxmd.com/read/28447585/metabolic-profiles-of-individuals-switched-to-second-line-antiretroviral-therapy-after-failing-standard-first-line-therapy-for-treatment-of-hiv-1-infection-in-a-randomized-controlled-trial
#1
Amanda H Yao, Cecilia L Moore, Poh Lian Lim, Jean-Michel Molina, Juan Sierra Madero, Stephen Kerr, Paddy Wg Mallon, Sean Emery, David A Cooper, Mark A Boyd
BACKGROUND: To investigate metabolic changes associated with second-line antiretroviral therapy (ART) following virological failure of first-line ART. METHODS: SECOND-LINE was an open-label randomized controlled trial. Participants were randomized 1:1 to receive ritonavir-boosted lopinavir (LPV/r) with 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTI-group) or raltegravir (RAL-group) Two hundred and ten participants had a dual energy X-ray absorptiometry (DXA)-scan at baseline, week 48 and 96...
April 27, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28427498/plasma-and-saliva-concentrations-of-abacavir-tenofovir-darunavir-and-raltegravir-in-hiv-1-infected-patients%C3%A2
#2
Eiko Yamada, Ritsuo Takagi, Yoshinari Tanabe, Hiroshi Fujiwara, Naoki Hasegawa, Shingo Kato
OBJECTIVE: We studied the relationships between plasma and saliva concentrations of antiretroviral drugs to explore whether saliva can be used for therapeutic drug monitoring (TDM). METHODS: Abacavir (ABC), tenofovir (TFV), darunavir (DRV), and raltegravir (RAL) in plasma and saliva from 30 HIV-1-infected patients were quantified using liquid chromatography-tandem mass spectrometry. RESULTS: Mean saliva-to-plasma concentration ratios were 0...
April 21, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28419778/single-and-multiple-dose-pharmacokinetics-of-once-daily-formulations-of-raltegravir
#3
Rajesh Krishna, Matthew L Rizk, Patrick Larson, Valerie Schulz, Filippos Kesisoglou, Radu Pop
A new once-daily formulation of raltegravir, an integrase strand transfer inhibitor indicated in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus-1 infection, is under development. Single-dose and steady-state pharmacokinetics of 1200 mg for 2 formulations of raltegravir were characterized in 2 open-label phase 1 studies in healthy male and female subjects aged 18 to 55 years. The new raltegravir 600-mg formulation had a higher relative bioavailability compared with the 400-mg tablets...
April 17, 2017: Clinical Pharmacology in Drug Development
https://www.readbyqxmd.com/read/28419270/raltegravir-plus-lamivudine-as-maintenance-therapy-in-suppressed-hiv-1-infected-patients-in-real-life-settings
#4
Giulia Cucchetto, Massimiliano Lanzafame, Stefano Nicolè, Emanuela Lattuada, Leonardo Calza, Ercole Concia
No abstract text is available yet for this article.
April 16, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28403052/second-and-third-line-antiretroviral-therapy-for-children-and-adolescents-a-scoping-review
#5
REVIEW
Erica Lazarus, Simone Nicol, Lisa Frigati, Martina Penazzato, Mark F Cotton, Elizabeth Centeno-Tablante, Avy Violari, Liesl Nicol
BACKGROUND: The World Health Organization identified a need for evidence to inform revision of second- and third-line antiretroviral therapy (ART) options in children failing ART. We performed an in-depth scoping review of all available literature on second-line and subsequent ART regimens in children younger than 18 years. METHODS: We comprehensively searched, without language or date limitations, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform and ClinicalTrials...
May 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28397245/interactions-between-integrase-inhibitors-and-human-arginase-1
#6
Lucia Lisi, Michela Pizzoferrato, Fabiola Teresa Miscioscia, Alessandra Topai, Pierluigi Navarra
The neuro-pathogenic mechanism(s) underlying HIV-associated neurocognitive disorders are mostly unknown. HIV-infected macrophages and microglial cells play a crucial role and the metabolic fate of L-arginine may be highly relevant for microglia activation. In this context Arginase (ARG), which uses L-arginine as substrate, can be on the same time a target and source of oxidative stress and inflammation. In the present study, we investigated whether Integrase Strand Transfer Inhibitors (INSTIs) share with the other antiretroviral drugs the ability to inhibit ARG activity...
April 11, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28395180/total-cellular-hiv-1-dna-decreases-after-switching-to-raltegravir-based-regimens-in-patients-with-suppressed-hiv-1-rna
#7
Barbara Rossetti, Genny Meini, Claudia Bianco, Silvia Lamonica, Annalisa Mondi, Simone Belmonti, Iuri Fanti, Nicoletta Ciccarelli, Simona Di Giambenedetto, Maurizio Zazzi, Andrea De Luca
BACKGROUND: The integrase inhibitor raltegravir has been used to intensify antiretroviral therapy in patients with undetectable plasma HIV-1RNA, resulting in variable perturbation of HIV-1 nucleic acids levels in peripheral blood. OBJECTIVES: We aimed at monitoring residual plasma HIV-1RNA and total cellular HIV-1DNA in virologically suppressed patients switching to raltegravir-based regimens. STUDY DESIGN: Fifty-eight subjects on protease inhibitor (PI) or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens, with plasma HIV-1RNA levels <40 copies/ml for ≥6 months and CD4 counts >200cells/μl for ≥12 months were enrolled...
March 23, 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/28390164/-efficacy-and-safety-of-nucleoside-sparing-regimen-based-on-raltegravir-and-ritonavir-boosted-darunavir-in-hiv-1-infected-treatment-experienced-patients
#8
Elżbieta Jabłonowska, Piotr Pulik, Anna Kalinowska, Jacek Gąsiorowski, Miłosz Parczewski, Monika Bociąga-Jasik, Łukasz Pulik, Ewa Siwak, Kamila Wójcik
AIM: To assess the efficacy and tolerability of dual therapy containing raltegravir (RAL) and ritonavir boosted darunavir (DRV/r) in HIV-1-infected treatment-experienced patients.ethod. Retrospective analysis of 81 HIV-1-infected treatment-experienced patients (56 male and 25 female, 5 Polish centers) who switched to RAL/DRV/r. RESULTS: The main reasons for the introduction of dual therapy were renal dysfunction (16/81 patients - 19.8%) and virologic failure on previous regimens (15/81 patients - 18...
April 8, 2017: Journal of Medical Virology
https://www.readbyqxmd.com/read/28375875/emergent-drug-resistance-with-integrase-strand-transfer-inhibitor-based-regimens-incidence-and-risk-factors
#9
Katherine J Lepik, P Richard Harrigan, Benita Yip, Lu Wang, Marjorie A Robbins, Wendy W Zhang, Junine Toy, Linda Akagi, Viviane Dias Lima, Silvia Guillemi, Julio S G Montaner, Rolando Barrios
OBJECTIVES: To estimate the incidence of and risk factors for emergent resistance to integrase inhibitors (INSTI) and nucleoside(-tide) reverse transcriptase inhibitors (NRTI) in HIV-1-infected adults receiving an INSTI plus two NRTIs. DESIGN: Retrospective cohort study. METHODS: Persons ≥19 years were included if they received their first prescription for raltegravir, elvitegravir or dolutegravir in British Columbia, Canada in 2012-2014, and were followed to 31-Dec-2015...
April 3, 2017: AIDS
https://www.readbyqxmd.com/read/28369593/drug-resistance-mutations-in-hiv-2-patients-failing-raltegravir-and-influence-on-dolutegravir-response
#10
Silvia Requena, Ana Treviño, Teresa Cabezas, Rosa Garcia-Delgado, María José Amengual, Ana Belén Lozano, María Peñaranda, Juan Manuel Fernández, Vicente Soriano, Carmen de Mendoza
Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir. Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded...
March 23, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28369189/association-of-the-hla-b-53-01-allele-with-drug-reaction-with-eosinophilia-and-systemic-symptoms-dress-syndrome-during-treatment-of-hiv-infection-with-raltegravir
#11
Mark Thomas, Chris Hopkins, Eamon Duffy, Daniel Lee, Pierre Loulergue, Diego Ripamonti, David A Ostrov, Elizabeth Phillips
Background.: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is a rare, severe adverse event during treatment with raltegravir. The occurrence of DRESS syndrome during treatment with other drugs is strongly associated with particular HLA alleles. Methods.: We performed HLA testing in 3 of the 5 patients previously reported to have developed raltegravir-induced DRESS syndrome and in 1 previously unreported patient. We then used virtual modeling to visualize interactions between raltegravir and the imputed HLA molecule...
May 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28362071/differential-effects-of-antiretrovirals-on-microbial-translocation-and-gut-microbiota-composition-of-hiv-infected-patients
#12
María J Villanueva-Millán, Patricia Pérez-Matute, Emma Recio-Fernández, José M Lezana Rosales, José A Oteo
INTRODUCTION: Increased bacterial translocation and alterations to gut microbiota composition have been described in HIV infection and contribute to immune activation and inflammation. These effects persist despite combined antiretroviral therapy (cART). However, the contribution of different cART combinations has not yet been investigated. The aim of this study was to analyse the long-term effects of different combinations of cART on bacterial translocation and gut microbiota composition in HIV-infected patients...
March 8, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28361525/a-rapid-validated-uv-hplc-method-for-the-simultaneous-determination-of-the-antiretroviral-compounds-darunavir-and-raltegravir-in-their-dosage-form
#13
G Estan-Cerezo, A García-Monsalve, L Soriano-Irigaray, F J Rodríguez-Lucena, A Navarro-Ruiz
OBJECTIVE: A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet detection has been developed for quantification of darunavir and raltegravir in their pharmaceutical dosage form. METHODS: The assay enables the measurement of both drugs with a linear calibration curve (R2= 0.999) over the concentration range 5-100 mg/L. The determination was performed on an analytical Tracer Excel 120 ODSB (15x0.4.6 cm) column at 35ºC...
March 29, 2017: Revista Española de Quimioterapia: Publicación Oficial de la Sociedad Española de Quimioterapia
https://www.readbyqxmd.com/read/28359840/samhd1-is-active-in-cycling-cells-permissive-to-hiv-1-infection
#14
Roger Badia, Maria Pujantell, Javier Torres-Torronteras, Luis Menéndez-Arias, Ramón Martí, Albert Ruzo, Eduardo Pauls, Bonaventura Clotet, Ester Ballana, José A Esté, Eva Riveira-Muñoz
SAMHD1 is a triphosphohydrolase that restricts HIV-1 by limiting the intracellular dNTP pool required for reverse transcription. Although SAMHD1 is expressed and active/unphosphorylated in most cell lines, its restriction activity is thought to be relevant only in non-cycling cells. However, an in depth evaluation of SAMHD1 function and relevance in cycling cells is required. Here, we show that SAMHD1-induced degradation by HIV-2 Vpx affects the dNTP pool and HIV-1 replication capacity in the presence of the 3'-azido-3'-deoxythymidine (AZT) in cycling cells...
June 2017: Antiviral Research
https://www.readbyqxmd.com/read/28356041/recent-advances-in-antiretroviral-agents-potent-integrase-inhibitors
#15
Mina Psichogiou, Garyphalia Poulakou, Dimitrios Basoulis, Dimitrios Paraskevis, Antonios Markogiannakis, George L Daikos
Integrase strand transfer inhibitors (INSTIs) belong to a novel class of antiretroviral agents that have emerged as the new first-line treatments. Three such compounds are currently available, raltegravir, elvitegravir, dolutegravir and two more under development, bictegravir and cabotegravir. These compounds share the same mode of action but exhibit different pharmacokinetic/ pharmacodynamic properties, and drug-drug interactions. A series of studies in the past decade have established their efficacy compared to previous regimens, both in treatment-naïve and experienced patients...
March 29, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28350300/impact-of-ccr5-integrase-and-protease-inhibitors-on-human-endothelial-cell-function-stress-inflammation-and-senescence
#16
Pauline Afonso, Martine Auclair, Martine Caron-Debarle, Jacqueline Capeau
BACKGROUND: Aging HIV-infected patients present an increased incidence of cardiovascular diseases, endothelial dysfunction being an early alteration. Some protease inhibitors (PI)s have been shown to experience risk of increased cardiovascular disease. We evaluated here the effects of CCR5 or integrase inhibitors as compared to PIs on endothelial functions in vitro. METHODS: Human coronary artery endothelial cells (HCAEC) from adult and old non-HIV infected donors were treated for 15 days with the CCR5 inhibitor maraviroc, the integrase inhibitors dolutegravir or raltegravir or the ritonavir-boosted-PIs, darunavir (DRV/r) or atazanavir (ATV/r), all at Cmax concentrations...
March 28, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28333231/tolerability-of-integrase-inhibitors-in-a-real-life-setting
#17
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
#18
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
#19
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...
May 1, 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
#20
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
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