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https://www.readbyqxmd.com/read/29474261/pharmacokinetics-short-term-safety-and-efficacy-of-the-approved-once-daily-darunavir-r-dosing-regimen-in-hiv-infected-children
#1
Diane E T Bastiaans, Sibyl P M Geelen, Eline G Visser, Michiel van der Flier, Clementien L Vermont, Angela P H Colbers, Monique Roukens, David M Burger, Annemarie M C van Rossum
In this multicenter pharmacokinetic study in HIV-infected children (6-12 years), we validated the approved once-daily darunavir/ritonavir dosing recommendations.The geometric mean darunavir area under the plasma concentration-time curve was 63.1 h.mg/l, substantially lower than the mean value observed in adults. However, all trough levels were adequate and short-term virological outcome was good. These data support the use of the darunavir/ritonavir once-daily dosing recommendations.
February 22, 2018: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/29473485/high-virologic-failure-rates-with-maraviroc-based-salvage-regimens-among-indian-patients-a-preliminary-analysis-maraviroc-effectiveness-in-hiv-1-subtype-c
#2
Sanjay Pujari, Sunil Gaikwad, Vivek Bele, Kedar Joshi, Digamber Dabhade
BACKGROUND: There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses. METHODS: We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history)...
January 2018: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/29469716/associated-conditions-in-patients-with-multiple-dermatofibromas-case-reports-and-literature-review
#3
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/29463535/grl-079-a-novel-p2-tp-thf-c5-alkylamine-and-p2-abt-containing-hiv-1-protease-inhibitor-is-extremely-potent-against-multi-drug-resistant-hiv-1-variants-including-hiv-drv-r-p51-and-has-a-high-genetic-barrier-against-the-emergence-of-resistant-variants
#4
Nicole S Delino, Manabu Aoki, Hironori Hayashi, Shin-Ichiro Hattori, Simon B Chang, Yuki Takamatsu, Cuthbert D Martyr, Debananda Das, Arun K Ghosh, Hiroaki Mitsuya
We identified four novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs), GRL-078, -079, -077, and -058, containing an alkylamine at the C5 position of P2-tetrahydropyrano-tetrahydrofuran (Tp-THF) and a P2' -cyclopropyl (Cp)(or isopropyl)-aminobenzothiazole (Abt). Their 50% effective concentrations (EC50 s) were 2.5-30 nM against wild-type HIV-1NL4-3 , 0.3-6.7 nM against HIV-2EHO , and 0.9-90 nM against laboratory-selected-PI-resistant HIV-1 and clinical HIV-1 variants resistant to multiple FDA-approved PIs (HIVMDR )...
February 20, 2018: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/29458132/therapeutic-drug-monitoring-in-treatment-experienced-hiv-infected-patients-receiving-darunavir-based-salvage-regimens-a-case-series
#5
Sébastien Landry, Chi-Nan Chen, Nimish Patel, Alice Tseng, Richard G Lalonde, Denis Thibeault, Steven Sanche, Nancy L Sheehan
Therapeutic drug monitoring (TDM) constitutes a compelling approach for the optimization of antiretroviral therapy in treatment-experienced HIV-1 patients. While various inhibitory indices have been proposed to predict virologic outcome, there is a lack of consensus on the clinical value of TDM. Here, we report the comparative results of TDM in 14 HIV-1-infected patients who had previously received at least two different PI-based regimens and who initiated darunavir (DRV)-based salvage therapy. Pharmacokinetic/pharmacodynamics (PK/PD) parameters were calculated for each subject...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29457713/probing-structural-changes-among-analogous-inhibitor-bound-forms-of-hiv-1-protease-and-a-drug-resistant-mutant-in-solution-by-nuclear-magnetic-resonance
#6
Shahid N Khan, John D Persons, Janet L Paulsen, Michel Guerrero, Celia A Schiffer, Nese Kurt-Yilmaz, Rieko Ishima
In the era of state-of-the-art inhibitor design and high-resolution structural studies, detection of significant but small protein structural differences in the inhibitor-bound forms is critical to further developing the inhibitor. Here, we probed differences in HIV-1 protease (PR) conformation among darunavir and four analogous inhibitor-bound forms and compared them with a drug-resistant mutant using nuclear magnetic resonance chemical shifts. Changes in amide chemical shifts of wild-type (WT) PR among these inhibitor-bound forms, ΔCSP, were subtle but detectable and extended >10 Å from the inhibitor-binding site, asymmetrically between the two subunits of PR...
February 19, 2018: Biochemistry
https://www.readbyqxmd.com/read/29447085/paritaprevir-ritonavir-ombitasvir-plus-dasabuvir-in-hiv-hcv-coinfected-patients-with-genotype-1-in-real-life-practice
#7
Juan A Pineda, Antonio Rivero-Juárez, Ignacio de Los Santos, Antonio Collado, Dolores Merino, Luis E Morano-Amado, María J Ríos, Montserrat Pérez-Pérez, Francisco Téllez, Rosario Palacios, Ana B Pérez, María Mancebo, Antonio Rivero, Juan Macías
Background Data on the efficacy, safety, and concomitant use with other drugs of the combination ritonavir-boosted paritaprevir/ombitasvir plus dasabuvir (PrOD) in HIV/HCV-coinfected patients in real life are limited. The objectives of this study were to analyze these topics in HIV/HCV-coinfected subjects bearing HCV genotype 1 (GT1). Methods One hundred and eighty-two HIV/HCV-coinfected patients with GT1 (87 1a, 71 1b, 23 other) treated with PrOD, plus ribavirin (RBV) in 119 cases, in routine clinical practice were analyzed...
February 15, 2018: HIV Clinical Trials
https://www.readbyqxmd.com/read/29444582/dolutegravir-based-regimens-are-active-in-integrase-strand-transfer-inhibitor-naive-patients-with-nucleoside-reverse-transcriptase-inhibitor-resistance
#8
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/29438199/changes-in-cerebral-function-parameters-with-maraviroc-intensified-antiretroviral-therapy-in-treatment-na%C3%A3-ve-hiv-positive-individuals-a-randomised-controlled-study
#9
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
https://www.readbyqxmd.com/read/29435471/hiv-1-drug-resistance-and-third-line-therapy-outcomes-in-patients-failing-second-line-therapy-in-zimbabwe
#10
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/29430854/darunavir-cobicistat-showing-similar-effectiveness-as-darunavir-ritonavir-monotherapy-despite-lower-trough-concentrations
#11
Alicia Gutierrez-Valencia, Maria Trujillo-Rodriguez, Tamara Fernandez-Magdaleno, Nuria Espinosa, Pompeyo Viciana, Luis F López-Cortés
INTRODUCTION: When darunavir (DRV) 800 mg is boosted with 150 mg cobicistat (DRVcobi ), DRV trough concentration (Ctrough ) is about 30% lower as compared to 100 mg ritonavir (DRVrtv ). DRVcobi shows similar virological efficacy as DRVrtv when combined with two nucleos(t)ide analogue reverse-transcriptase inhibitors, but it is unknown whether a lower DRV Ctrough would undermine the effectiveness of DRVcobi when given as monotherapy (mtDRVcobi ). METHODS: Prospective observational study on virologically suppressed HIV-infected subjects who switched to mtDRVcobi ...
February 2018: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29429441/characteristics-and-early-outcomes-of-children-and-adolescents-treated-with-darunavir-ritonavir-raltegravir-or-etravirine-containing-antiretroviral-therapy-in-the-western-cape-province-of-south-africa
#12
J Nuttall, V Pillay
BACKGROUND: There is an increasing need for third-line treatment regimens in HIV-infected children with antiretroviral treatment (ART) failure. Data are limited on darunavir/ritonavir (DRV/r)-, raltegravir (RAL)- and etravirine (ETR)-containing regimens in treatment-experienced children from resource-constrained settings receiving these drugs as part of routine care. OBJECTIVE: To describe the characteristics and early outcomes of treatment-experienced children (<20 years of age) in the Western Cape Province of South Africa treated with DRV/r-, RAL- or ETR-containing regimens...
February 1, 2018: South African Medical Journal, Suid-Afrikaanse Tydskrif Vir Geneeskunde
https://www.readbyqxmd.com/read/29395300/effect-of-body-weight-and-composition-on-efavirenz-atazanavir-or-darunavir-concentration
#13
Célia Lloret-Linares, Yasmin Rahmoun, Amanda Lopes, Dorothée Chopin, Guy Simoneau, Andrew Green, Brigitte Delhotal, Hélène Sauvageon, Stéphane Mouly, Jean-François Bergmann, Pierre-Olivier Sellier
BACKGROUND: To compare the steady state plasma concentrations (Css) of three antiretroviral drugs in both normal and overweight patients, and to determine the relationship between Css and fat mass (FM) or lean body mass. METHODS: Patients treated for more than 6 months once daily with one of the antiretroviral drugs: efavirenz (EFV) 600mg, atazanavir boosted with ritonavir (ATV-r) 300mg/100mg, or darunavir boosted with ritonavir (DRV-r) 800mg/100mg, combined with two nucleoside analogues, were enrolled prospectively...
November 2, 2017: Thérapie
https://www.readbyqxmd.com/read/29388732/long-term-effectiveness-of-recommended-boosted-protease-inhibitor-based-antiretroviral-therapy-in-europe
#14
J R Santos, A Cozzi-Lepri, A Phillips, S De Wit, C Pedersen, P Reiss, A Blaxhult, A Lazzarin, M Sluzhynska, C Orkin, C Duvivier, J Bogner, P Gargalianos-Kakolyris, P Schmid, G Hassoun, I Khromova, M Beniowski, V Hadziosmanovic, D Sedlacek, R Paredes, J D Lundgren
OBJECTIVES: The aim of the study was to evaluate the long-term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)-, darunavir/ritonavir (DRV/r)-, and lopinavir/ritonavir (LPV/r)-containing regimens. METHODS: Data were analysed for 5678 EuroSIDA-enrolled patients starting a DRV/r-, ATZ/r- or LPV/r-containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART-naïve subjects (8%) at ritonavir-boosted protease inhibitor (PI/r) initiation; (2) ART-experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV-1 RNA copies/mL; and (3) ART-experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL...
February 1, 2018: HIV Medicine
https://www.readbyqxmd.com/read/29385867/combination-therapy-with-tenofovir-disoproxil-fumarate-emtricitabine-elvitegravir-cobicistat-plus-darunavir-once-daily-in-antiretroviral-naive-and-treatment-experienced-patients-a-retrospective-review
#15
Mark J Naccarato, Deborah M Yoong, Ignatius W Fong, Kevin A Gough, Marian A Ostrowski, Darrell H S Tan
BACKGROUND: Patients with drug-resistant HIV often require complex antiretroviral regimens. However, combining fixed-dose combination tablets such as tenofovir-disoproxil-fumarate, emtricitabine, and cobicistat-boosted elvitegravir (TDF/FTC/EVG/cobi) with darunavir (DRV) can provide a simple, once-daily (QD), 2-tablet regimen for patients with drug-resistant HIV. Primary objective was to determine the percentage of patients with HIV-1 RNA <40 copies/mL at 48 weeks. METHODS: We performed a retrospective chart review of patients initiated on TDF/FTC/EVG/cobi plus DRV...
January 2018: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/29373758/drug-drug-interactions-between-pa-824-and-darunavir-based-on-pharmacokinetics-in-rats-by-lc-ms-ms
#16
Libin Wang, Jun Zhao, Ruitao Zhang, Le Mi, Xin Shen, Nan Zhou, Tian Feng, Juan Jing, Xueying Liu, Shengyong Zhang
Currently, patients with co-infection with HIV and tuberculosis are treated with more than one drug. PA-824 a new chemical entity and a member of a class of compounds known as nitroimidazo-oxazines, has significant antituberculosis activity and a unique mechanism of action. Darunavir (PrezistaTM) is a new protease inhibitor of HIV-1. A simple, sensitive and rapid LC-MS-MS method has been developed and validated for simultaneous determination of PA-824 and darunavir. Chromatographic separation was achieved on Agilent Eclipse plus C18 column (100 mm × 2...
January 24, 2018: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/29365125/decreased-darunavir-concentrations-during-once-daily-co-administration-with-maraviroc-and-raltegravir-optiprim-anrs-147-trial
#17
Claire Pressiat, Déborah Hirt, Jean-Marc Treluyer, Yi Zheng, Philippe Morlat, Alice Naqvi, Laurent Tran, Jean-Paul Viard, Véronique Avettand-Fenoel, Christine Rouzioux, Laurence Meyer, Antoine Cheret
Background: The OPTIPRIM-ANRS 147 trial compared intensive combination ART (darunavir/ritonavir, tenofovir disoproxil fumarate/emtricitabine, raltegravir and maraviroc) started early during primary HIV-1 infection with standard tritherapy with darunavir/ritonavir, tenofovir disoproxil fumarate and emtricitabine. From month 6 to 18, the percentage of viral load values <50 copies/mL was lower in the pentatherapy arm than in the tritherapy arm. Here we compared antiretroviral drug concentrations between the two arms...
January 22, 2018: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/29342239/hplc-estimation-ex-vivo-everted-sac-permeability-and-in-vivo-pharmacokinetic-studies-of-darunavir
#18
Vasanti M Suvarna, Preeti C Sangave
Darunavir ethanolate (DRV) is an efficient protease inhibitor (PI) used in the treatment of human immunodeficiency virus (HIV) type-1 patients. An isocratic reversed-phase HPLC method was developed to monitor concentration of darunavir in in vitro intestinal fluid samples in everted sac absorption model in the presence of bioenhancers, viz., piperine, quercetin, naringenin. The method was validated and successfully applied to everted sac and pharmacokinetic studies in rats. The absorption profiles of DRV and apparent permeability coefficients were determined...
January 12, 2018: Journal of Chromatographic Science
https://www.readbyqxmd.com/read/29335428/analysis-of-the-hiv-2-protease-s-adaptation-to-various-ligands-characterization-of-backbone-asymmetry-using-a-structural-alphabet
#19
Dhoha Triki, Mario Enrique Cano Contreras, Delphine Flatters, Benoit Visseaux, Diane Descamps, Anne-Claude Camproux, Leslie Regad
The HIV-2 protease (PR2) is a homodimer of 99 residues with asymmetric assembly and binding various ligands. We propose an exhaustive study of the local structural asymmetry between the two monomers of all available PR2 structures complexed with various inhibitors using a structural alphabet approach. On average, PR2 exhibits asymmetry in 31% of its positions-i.e., exhibiting different backbone local conformations in the two monomers. This asymmetry was observed all along its structure, particularly in the elbow and flap regions...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29318459/incidence-and-predictors-of-single-drug-discontinuation-according-to-the-presence-of-hcv-coinfection-in-hiv-patients-from-the-icona-foundation-cohort-study
#20
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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