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Darunavir

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https://www.readbyqxmd.com/read/29020293/dual-therapy-with-darunavir-and-ritonavir-plus-lamivudine-versus-triple-therapy-with-darunavir-and-ritonavir-plus-tenofovir-disoproxil-fumarate-and-emtricitabine-or-abacavir-and-lamivudine-for-maintenance-of-hiv-1-viral-suppression-randomised-open-label-non
#1
Federico Pulido, Esteban Ribera, María Lagarde, Ignacio Pérez-Valero, Rosario Palacios, José A Iribarren, Antoni Payeras, Pere Domingo, José Sanz, Miguel Cervero, Adrián Curran, Francisco J Rodríguez-Gómez, María J Téllez, Pablo Ryan, Pilar Barrufet, Hernando Knobel, Antonio Rivero, Belén Alejos, María Yllescas, José R Arribas
Background: Our objective was to assess the therapeutic non-inferiority of dual therapy with darunavir/ritonavir and lamivudine compared to triple therapy with darunavir/ritonavir plus tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine for maintenance of HIV-1 viral suppression. Methods: 48-week, multicenter, open-label, non-inferiority trial (margin 12%). Patients with HIV-1 RNA <50 copies/mL for ≥6 months on triple therapy with darunavir/ritonavir and two nucleos(t)ides (tenofovir disoproxil fumarate and emtricitabine or abacavir and lamivudine), with no resistance, were randomized to continue therapy (n=128) or switch to darunavir/ritonavir and lamivudine (n=129)...
August 17, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28993180/efficacy-and-safety-of-switching-from-boosted-protease-inhibitors-plus-emtricitabine-and-tenofovir-disoproxil-fumarate-regimens-to-single-tablet-darunavir-cobicistat-emtricitabine-and-tenofovir-alafenamide-at-48-weeks-in-adults-with-virologically-suppressed
#2
Chloe Orkin, Jean-Michel Molina, Eugenia Negredo, José R Arribas, Joseph Gathe, Joseph J Eron, Erika Van Landuyt, Erkki Lathouwers, Veerle Hufkens, Romana Petrovic, Simon Vanveggel, Magda Opsomer
BACKGROUND: Simplified regimens with reduced pill burden and fewer side-effects are desirable for people living with HIV. We investigated the efficacy and safety of switching to a single-tablet regimen of darunavir, cobicistat, emtricitabine, and tenofovir alafenamide versus continuing a regimen of boosted protease inhibitor, emtricitabine, and tenofovir disoproxil fumarate. METHODS: EMERALD was a phase-3, randomised, active-controlled, open-label, international, multicentre trial, done at 106 sites across nine countries in North America and Europe...
October 5, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28991888/commonly-prescribed-antiretroviral-therapy-regimens-and-incidence-of-aids-defining-neurological-conditions
#3
Ellen C Caniglia, Andrew Phillips, Kholoud Porter, Caroline A Sabin, Alan Winston, Roger Logan, John Gill, Marie-Anne Vandenhende, Diana Barger, Sara Lodi, Santiago Moreno, José Ramón Arribas, Antonio Pacheco, Sandra W Cardoso, George Chrysos, Charalabos Gogos, Sophie Abgrall, Dominique Costagliola, Laurence Meyer, Remonie Seng, Ard van Sighem, Peter Reiss, Roberto Muga, Santiago Pérez Hoyos, Dominique Braun, Christoph Hauser, Pilar Barrufet, Maria Leyes, Janet Tate, Amy Justice, Miguel A Hernán
BACKGROUND: The differential effects of commonly prescribed combined antiretroviral therapy (cART) regimens on AIDS-defining neurological conditions (neuroAIDS) remain unknown. SETTING: Prospective cohort studies of HIV-positive individuals from Europe and the Americas included in the HIV-CAUSAL Collaboration. METHODS: Individuals who initiated a first-line cART regimen in 2004 or later containing a nucleoside reverse transcriptase inhibitor (NRTI) backbone and either atazanavir, lopinavir, darunavir, or efavirenz were followed from cART initiation until death, lost to follow-up, pregnancy, the cohort-specific administrative end of follow-up, or the event of interest, whichever occurred earliest...
October 4, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28988509/darunavir-for-use-in-pregnant-women-with-hiv
#4
Robert Pope, Angela Kashuba
Combination antiretroviral therapy is recommended during pregnancy to decrease the rate of HIV transmission to the baby and reduce morbidity in the mother. More than 50% of women are prescribed a protease inhibitor-based regimen during pregnancy. Darunavir was recently reclassified as a first-line protease inhibitor for use in pregnancy in the US Department of Health and Human Services Perinatal Guidelines. Areas covered: This is a brief review of the use of protease inhibitor therapy during pregnancy, and a discussion of darunavir's utility in this area...
October 7, 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28969531/kidney-transplant-in-a-human-immunodeficiency-virus-positive-patient-case-report-of-drug-interactions
#5
Mümtaz Yılmaz, Deniz Gökengin, Osman Bozbıyık, Cüneyt Hoşcoşkun, Ayşe Uyan, Hüseyin Töz
End-stage renal disease in the human immunodeficiency virus-positive population is increasing. Kidney transplant is the optimal therapy for this population rather than dialysis modalities if some criteria are met. These include undetectable plasma human immunodeficiency virus RNA, CD4 cell count over 200 cells/μL, and the absence of any AIDS-defining illness. Here, we describe the first living-donor kidney transplant in a human immunodeficiency virus-positive recipient in Turkey. The patient, a 52-year-old male diagnosed as human immunodeficiency virus positive, was on antiretroviral therapy, which consisted of 400 mg twice daily darunavir, 100 mg/day ritonavir, and 50 mg/day dolutegravir...
September 30, 2017: Experimental and Clinical Transplantation
https://www.readbyqxmd.com/read/28964268/a-dual-regimen-of-ritonavir-darunavir-plus-dolutegravir-for-rescue-or-simplification-of-rescue-therapy-48%C3%A2-weeks-observational-data
#6
Amedeo F Capetti, Maria Vittoria Cossu, Giancarlo Orofino, Gaetana Sterrantino, Giovanni Cenderello, Giuseppe V De Socio, Anna Maria Cattelan, Alessandro Soria, Stefano Rusconi, Niccolò Riccardi, Gian Maria Baldin, Fosca P Niero, Giorgio Barbarini, Giuliano Rizzardini
BACKGROUND: Dolutegravir (DTG) plus darunavir/ritonavir (DRV/r) is a simple combination of drugs that has the best genetic barrier to HIV-1 resistance and may be fit for salvage therapy. METHODS: All HIV-1-infected subjects treated with DTG plus DRV/r between March 2014 and September 2015 in eight Italian centres were included in the analysis. The main metabolic data, efficacy parameters and safety data routinely collected were provided. This observational study is aimed to assess the efficacy of such approach...
September 30, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28959444/efficacy-of-raltegravir-etravirine-and-darunavir-ritonavir-for-treatment-experienced-hiv-patients-from-a-non-urban-clinic-population-in-the-united-states
#7
Andrew M Ebers, Yusra Alkabab, Brian Wispelwey, Rebecca Dillingham, Xin-Qun Wang, Julie Schexnayder, Scott K Heysell
BACKGROUND: The regimen of raltegravir (RAL), ritonavir-boosted darunavir (DAR/r), and etravirine (ETR) for HIV treatment-experienced patients in a non-clinical trial setting in the rural/semi-urban United States had not been evaluated. OBJECTIVE: A retrospective cohort analysis was performed of adult patients prescribed the regimen from 2008 to 2013 at a HIV clinic serving such a population. RESULTS: In all, 51 patients met inclusion criteria including 15 with suppressed viral loads at regimen initiation...
September 2017: Therapeutic Advances in Infectious Disease
https://www.readbyqxmd.com/read/28954087/drug-induced-hypersensitivity-syndrome-after-initiation-of-darunavir-and-raltegravir
#8
Walter de Araujo Eyer-Silva, Maria Alessandra Leite Freire, Guilherme Almeida Rosa da Silva
No abstract text is available yet for this article.
July 2017: Revista da Sociedade Brasileira de Medicina Tropical
https://www.readbyqxmd.com/read/28948564/darunavir-loaded-lipid-nanoparticles-for-targeting-to-hiv-reservoirs
#9
Jagruti Desai, Hetal Thakkar
Darunavir has a low oral bioavailability (37%) due to its lipophilic nature, metabolism by cytochrome P450 enzymes and P-gp efflux. Lipid nanoparticles were prepared in order to overcome its low bioavailability and to increase the binding efficacy of delivery system to the lymphoid system. Darunavir-loaded lipid nanoparticles were prepared using high-pressure homogenization technique. Hydrogenated castor oil was used as lipid. Peptide, having affinity for CD4 receptors, was grafted onto the surface of nanoparticles...
September 25, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28948180/safety-and-efficacy-of-ombitasvir-paritaprevir-with-ritonavir-%C3%A2-dasabuvir-with-or-without-ribavirin-in-patients-with-human-immunodeficiency-virus-1-and-hepatitis-c-virus-genotype-1-or-genotype-4-coinfection-turquoise-i-part-2
#10
Jürgen K Rockstroh, Chloe Orkin, Rolando M Viani, David Wyles, Anne F Luetkemeyer, Adriano Lazzarin, Ruth Soto-Malave, Mark R Nelson, Sanjay R Bhagani, Hartwig H F Klinker, Giuliano Rizzardini, Pierre-Marie Girard, Cristina Tural, Nancy S Shulman, Niloufar Mobashery, Yiran B Hu, Linda M Fredrick, Tami Pilot-Matias, Roger Trinh, Edward Gane
BACKGROUND: Ombitasvir, paritaprevir with ritonavir, and dasabuvir (OBV/PTV/r ± DSV) ±ribavirin (RBV) are approved to treat hepatitis C virus (HCV) genotype 1 and 4 infection. Here, we investigate the safety and efficacy of OBV/PTV/r + DSV ±RBV for HCV genotype 1, and OBV/PTV/r + RBV for HCV genotype 4, in human immunodeficiency virus (HIV)-1 coinfected patients with or without compensated cirrhosis. METHODS: TURQUOISE-I, Part 2 is a phase 3 multicenter study...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28947797/grl-09510-a-unique-p2-crown-tetrahydrofuranylurethane-containing-hiv-1-protease-inhibitor-maintains-its-favorable-antiviral-activity-against-highly-drug-resistant-hiv-1-variants-in-vitro
#11
Masayuki Amano, Pedro Miguel Salcedo-Gómez, Ravikiran S Yedidi, Nicole S Delino, Hirotomo Nakata, Kalapala Venkateswara Rao, Arun K Ghosh, Hiroaki Mitsuya
We report that GRL-09510, a novel HIV-1 protease inhibitor (PI) containing a newly-generated P2-crown-tetrahydrofuranylurethane (Crwn-THF), a P2'-methoxybenzene, and a sulfonamide isostere, is highly active against laboratory and primary clinical HIV-1 isolates (EC50: 0.0014-0.0028 μM) with minimal cytotoxicity (CC50: 39.0 μM). Similarly, GRL-09510 efficiently blocked the replication of HIV-1NL4-3 variants, which were capable of propagating at high-concentrations of atazanavir, lopinavir, and amprenavir (APV)...
September 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28926404/metabolic-health-across-the-body-mass-index-spectrum-in-hiv-infected-and-hiv-uninfected-men
#12
Jordan E Lake, Xiuhong Li, Frank J Palella, Kristine M Erlandson, Dorothy Wiley, Lawrence Kingsley, Lisa P Jacobson, Todd T Brown
OBJECTIVES: In the general population, metabolic health (MH) often declines as body mass index (BMI) increases. However, some obese individuals maintain MH. HIV and antiretroviral therapy (ART) have been associated with metabolic disturbances. We hypothesized that HIV-infected (HIV+) men on suppressive ART experience less MH than HIV-uninfected (HIV-) men across all BMI categories. DESIGN/METHODS: In a cross-sectional analysis of 1018 HIV+ and 1092 HIV- men enrolled in the Multicenter AIDS Cohort Study, Poisson regression with robust variance determined associations between HIV serostatus and MH prevalence (defined as meeting 2 of 5 NCEP/ATP III metabolic syndrome criteria), adjusting for age, race, BMI category, smoking and hepatitis C virus infection status...
September 18, 2017: AIDS
https://www.readbyqxmd.com/read/28915040/elucidating-the-interdependence-of-drug-resistance-from-combinations-of-mutations
#13
Debra A Ragland, Troy W Whitfield, Sook-Kyung Lee, Ronald Swanstrom, Konstantin B Zeldovich, Nese Kurt Yilmaz, Celia A Schiffer
HIV-1 protease is responsible for the cleavage of 12 non-homologous sites within the Gag and Gag-Pro-Pol polyproteins in the viral genome. Under the selective pressure of protease inhibition, the virus evolves mutations within (primary) and outside of (secondary) the active site allowing the protease to process substrates while simultaneously countering inhibition. The primary protease mutations impede inhibitor binding directly, while the secondary mutations are considered accessory mutations that compensate for a loss in fitness...
September 15, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28895059/central-nervous-system-penetrating-antiretrovirals-impair-energetic-reserve-in-striatal-nerve-terminals
#14
Kelly L Stauch, Katy Emanuel, Benjamin G Lamberty, Brenda Morsey, Howard S Fox
The use of antiretroviral (ARV) drugs with central nervous system (CNS) penetration effectiveness (CPE) may be useful in the treatment of HIV-associated neurocognitive disorder (HAND) as well as targeting a CNS reservoir in strategies to achieve a functional cure for HIV. However, increased cognitive deficits are linked to at least one of these drugs (efavirenz). As mitochondrial dysfunction has been found with a number of ARVs, and as such can affect neuronal function, the objective of this study was to assess the effects of ARV with high CPE for toxicological profiles on presynaptic nerve terminal energy metabolism...
September 11, 2017: Journal of Neurovirology
https://www.readbyqxmd.com/read/28884279/primary-hiv-infection-clinical-presentation-testing-and-treatment
#15
REVIEW
Aurélia Henn, Clara Flateau, Sébastien Gallien
PURPOSE OF REVIEW: The purpose of this review was to provide current data on clinical presentation, diagnosis, and treatment of primary HIV infection (PHI). RECENT FINDINGS: In 65 to 95% of cases, PHI causes acute retroviral syndrome presenting with unspecific flu-like symptoms. Symptomatic PHI was associated with a faster clinical and immunological progression of HIV infection. Point-of-care tests remain less sensitive than fourth-generation immunoassays (IA) in PHI, especially after tenofovir-based prophylaxis use...
September 7, 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28875397/boceprevir-and-antiretroviral-pharmacokinetic-interactions-in-hiv-hcv-co-infected-persons-aids-clinical-trials-group-study-a5309s
#16
Jennifer J Kiser, Darlene Lu, Susan L Rosenkranz, Gene D Morse, Robin DiFrancesco, Kenneth E Sherman, Adeel A Butt
OBJECTIVE: The objective of this study was to determine the magnitude of drug interactions between the hepatitis C virus (HCV) protease inhibitor boceprevir (BOC) and antiretroviral (ARV) agents in persons with HIV/HCV co-infection. METHODS: Participants taking two nucleos(t)ide analogs with either efavirenz, raltegravir, or ritonavir-boosted atazanavir, darunavir, or lopinavir underwent intensive pharmacokinetic (PK) sampling for ARV 2 weeks before (week 2) and 2 weeks after initiating BOC (week 6) and for BOC at week 6...
September 5, 2017: Drugs in R&D
https://www.readbyqxmd.com/read/28861811/differential-effects-of-antiretroviral-drugs-on-neurons-in-vitro-roles-for-oxidative-stress-and-integrated-stress-response
#17
Anna L Stern, Rebecca N Lee, Nina Panvelker, Jiean Li, Jenna Harowitz, Kelly L Jordan-Sciutto, Cagla Akay-Espinoza
Mounting evidence suggests that antiretroviral drugs may contribute to the persistence of HIV-associated neurocognitive disorders (HAND), which impact 30%-50% of HIV-infected patients in the post-antiretroviral era. We previously reported that two first generation HIV protease inhibitors, ritonavir and saquinavir, induced oxidative stress, with subsequent neuronal death in vitro, which was reversed by augmentation of the endogenous antioxidant response by monomethyl fumarate. We herein determined whether two newer-generation PIs, darunavir and lopinavir, were deleterious to neurons in vitro...
August 31, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28859438/pharmacokinetics-of-once-daily-dolutegravir-and-ritonavir-boosted-darunavir-in-hiv-patients-the-dualis-study
#18
Christoph D Spinner, Tim Kümmerle, Ivanka Krznaric, Olaf Degen, Christiane Schwerdtfeger, Alexander Zink, Eva Wolf, Hartwig H F Klinker, Christoph Boesecke
No abstract text is available yet for this article.
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28856025/efficacy-of-prompt-initiation-of-antiretroviral-therapy-in-the-treatment-of-hemophagocytic-lymphohistiocytosis-triggered-by-uncontrolled-human-immunodeficiency-virus
#19
Bryan P Fitzgerald, Amy L Wojciechowski, Rajinder P S Bajwa
Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening, rapidly progressive hematologic disorder involving uncontrolled immune system activation. HLH has been associated with viral infections, including human immunodeficiency virus (HIV) infections. We report a case of a critically ill 30-year-old female who was hospitalized with HIV-associated HLH, with a CD4 count of 4 cells/mL and HIV viral load of 1,842,730 copies/mL. After ruling out other potential infectious causes of HLH, antiretroviral therapy (ART) was initiated with darunavir, ritonavir, tenofovir, and emtricitabine...
2017: Case Reports in Critical Care
https://www.readbyqxmd.com/read/28843613/evolution-of-inhibitor-resistant-natural-mutant-forms-of-hiv-1-protease-probed-by-pre-steady-state-kinetic-analysis
#20
Maria Yu Zakharova, Alexandra A Kuznetsova, Elena N Kaliberda, Maria A Dronina, Alexander V Kolesnikov, Arina V Kozyr, Ivan V Smirnov, Lev D Rumsh, Olga S Fedorova, Dmitry G Knorre, Alexander G Gabibov, Nikita A Kuznetsov
Pre-steady state kinetic analysis of mechanistic features of substrate binding and processing is crucial for insight into the evolution of inhibitor-resistant forms of HIV-1 protease. These data may provide a correct vector for rational drug design assuming possible intrinsic dynamic effects. These data should also give some clues to the molecular mechanism of protease action and resistance to inhibitors. Here we report pre-steady state kinetics of the interaction of wild type or mutant forms of HIV-1 protease with a FRET-labeled peptide...
August 23, 2017: Biochimie
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