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https://www.readbyqxmd.com/read/28525359/i36t%C3%A2-t-mutation-in-south-african-subtype-c-c-sa-hiv-1-protease-significantly-alters-protease-drug-interactions
#1
Sibusiso B Maseko, Eden Padayachee, Thavendran Govender, Yasien Sayed, Gert Kruger, Glenn E M Maguire, Johnson Lin
The efficacy of HIV-1 protease inhibition therapies is often compromised by the emergence of mutations in the protease molecule that reduces the binding affinity of inhibitors while maintaining viable catalytic activity and affinity for natural substrates. In the present study, we used a recombinant HIV-1 C-SA protease and a recently reported variant for inhibition (Ki, IC50) and thermodynamic studies against nine clinically used inhibitors. This is the first time that binding free energies for C-SA PR and the mutant are reported...
May 19, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28522147/cardiovascular-risk-in-advanced-na%C3%A3-ve-hiv-infected-patients-starting-antiretroviral-therapy-comparison-of-three-different-regimens-prevaleat-ii-cohort
#2
Paolo Maggi, Chiara Bellacosa, Armando Leone, Anna Volpe, Elena Delfina Ricci, Nicoletta Ladisa, Stefania Cicalini, Elisabetta Grilli, Rosaria Viglietti, Antonio Chirianni, Lara Ines Bellazzi, Renato Maserati, Canio Martinelli, Paola Corsi, Benedetto Maurizio Celesia, Federica Sozio, Gioacchino Angarano
BACKGROUND AND AIMS: PREVALEAT (PREmature VAscular LEsions and Antiretroviral Therapy) II is a multicenter, longitudinal cohort study aimed at the evaluation of cardiovascular risk among advanced HIV-positive, treatment-naïve patients starting their first therapy. We hypothesized that these patients, present a higher cardiovascular (CV) risk. METHODS: The study included all consecutive naïve patients with less than 200 CD4 cells/ml starting antiretroviral therapy...
May 5, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/28520611/treatment-outcomes-of-third-line-antiretroviral-regimens-in-hiv-infected-thai-adolescents
#3
Wasana Prasitsuebsai, Jiratchaya Sophonphan, Kulkanya Chokephaibulkit, Jurai Wongsawat, Suparat Kanjanavanit, Pope Kosalaraksa, Chaiwat Ngampiyakul, Pakarat Sangkla, Rawiwan Hansudewechakul, Stephen J Kerr, Thanyawee Puthanakit, Jintanat Ananworanich
BACKGROUND: Efficacy and safety data of third-line antiretroviral (ARV) regimens in adolescents are limited. METHODOLOGY: This study enrolled HIV-infected Thais who were treated with third-line regimens consisting of darunavir/ritonavir (DRV/r), etravirine (ETR), tipranavir/ritonavir (TPV/r) or raltegravir (RAL). RESULTS: Fifty-four adolescents 2-17 years of age were enrolled from 8 sites and followed for 48 weeks. Reasons for switch were second-line failure (n=44) and toxicity to second-line regimens (n=10)...
May 16, 2017: Pediatric Infectious Disease Journal
https://www.readbyqxmd.com/read/28520610/candidates-for-inclusion-in-a-universal-antiretroviral-regimen-dolutegravir
#4
Pedro Cahn
PURPOSE OF REVIEW: The review addresses the role of dolutegravir (DTG) in first-line therapy. In the era of test and treat, where United Nations AIDS Program and WHO have set the ambitious targets of 90/90/90, new efficacious, well tolerated, and simple therapeutic options are needed. RECENT FINDINGS: DTG has been tested in large clinical trials in treatment-naïve patients, showing noninferiority to raltegravir and superiority compared with efavirenz and ritonavir-boosted darunavir, respectively...
May 16, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28484975/a-clinical-cassette-dosing-study-for-evaluating-the-contribution-of-hepatic-oatps-and-cyp3a-to-drug-drug-interactions
#5
Takashi Yoshikado, Kazuya Maeda, Sawako Furihata, Hanano Terashima, Takeshi Nakayama, Keiko Ishigame, Kazunobu Tsunemoto, Hiroyuki Kusuhara, Ken-Ichi Furihata, Yuichi Sugiyama
PURPOSE: To demonstrate the relative importance of organic anion-transporting polypeptides (OATPs) and cytochrome P450 3A (CYP3A) in the hepatic elimination of substrate drugs. METHODS: A cocktail of subtherapeutic doses of bosentan, repaglinide, clarithromycin, darunavir, simeprevir, and midazolam (CYP3A probe) was administered orally to eight healthy volunteers. Rifampicin (OATP inhibitor; 600 mg, p.o.) and itraconazole (CYP3A inhibitor; 200 mg, i.v.) were coadministered with the cocktail in the second and third phases, respectively...
May 8, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28482097/once-daily-atazanavir-cobicistat-and-darunavir-cobicistat-exposure-over-72%C3%A2-h-post-dose-in-plasma-urine-and-saliva-contribution-to-drug-pharmacokinetic-knowledge
#6
Emilie R Elliot, Alieu Amara, Nicole Pagani, Laura Else, Graeme Moyle, Alex Schoolmeesters, Chris Higgs, Saye Khoo, Marta Boffito
No abstract text is available yet for this article.
May 6, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28477212/efficacy-and-tolerability-of-switching-to-a-dual-therapy-with-darunavir-ritonavir-plus-raltegravir-in-hiv-infected-patients-with-hiv-1-rna-%C3%A2-50%C3%A2-cp-ml
#7
Giordano Madeddu, Stefano Rusconi, Alessandro Cozzi-Lepri, Simona Di Giambenedetto, Stefano Bonora, Alessia Carbone, Andrea De Luca, Nicola Gianotti, Antonio Di Biagio, Andrea Antinori
BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitors (NRTI) toxicity may represent a threat for long-term success of combined antiretroviral therapy. Some studies have suggested a possible improvement of NRTI-related toxicity after switching to NRTI-sparing regimens. OBJECTIVES: We aimed to explore the efficacy and tolerability of switching to darunavir/ritonavir (DRV/r) plus raltegravir (RAL) while having a viral load (VL) ≤50 copies/mL in the clinical setting...
May 5, 2017: Infection
https://www.readbyqxmd.com/read/28449051/viral-kinetics-in-semen-with-different-antiretroviral-families-in-treatment-na%C3%A3-ve-hiv-infected-patients-a-randomized-trial
#8
Alicia Gutierrez-Valencia, Omar J Benmarzouk-Hidalgo, Inmaculada Rivas-Jeremías, Nuria Espinosa, María Trujillo-Rodríguez, Tamara Fernandez-Magdaleno, Pompeyo Viciana, Luis F López-Cortés
Background: There are several regimens for starting antiretroviral treatment, but it remains unknown whether either of them is more advantageous regarding the time course and magnitude of HIV-RNA decay in semen. Objective: To evaluate the differential effect of different antiretroviral drug families on viral kinetics in seminal plasma of treatment-naïve HIV-infected patients. Methods: Phase II, randomized, open-label study in which participants were randomized 1:1:1 to receive tenofovir-DF plus emtricitabine, and either cobicistat-boosted elvitegravir (EVGcobi), rilpivirine (RPV), or ritonavir-boosted darunavir (DRVrtv)...
April 25, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28427498/plasma-and-saliva-concentrations-of-abacavir-tenofovir-darunavir-and-raltegravir-in-hiv-1-infected-patients%C3%A2
#9
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/28426519/toward-a-universal-antiretroviral-regimen-special-considerations-of-pregnancy-and-breast-feeding
#10
Amy L Slogrove, Polly Clayden, Elaine J Abrams
PURPOSE OF REVIEW: As optimized antiretroviral therapy (ART) regimens are prepared for introduction in low-income and middle-income countries (LMIC), we consider the current evidence related to dosing, efficacy and safety during pregnancy and breastfeeding of next-generation first-line and second-line ART regimens proposed for imminent introduction in the global marketplace. RECENT FINDINGS: Pregnancy pharmacokinetic considerations include potentially insufficient efavirenz exposure if dosed at 400 mg/day, the need for twice daily darunavir dosing and the paucity of data related to tenofovir alafenamide and dolutegravir dosing, safety and efficacy...
April 19, 2017: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/28418652/design-and-development-of-highly-potent-hiv-1-protease-inhibitors-with-a-crown-like-oxotricyclic-core-as-the-p2-ligand-to-combat-multidrug-resistant-hiv-variants
#11
Arun K Ghosh, Kalapala Venkateswara Rao, Prasanth R Nyalapatla, Heather L Osswald, Cuthbert D Martyr, Manabu Aoki, Hironori Hayashi, Johnson Agniswamy, Yuan-Fang Wang, Haydar Bulut, Debananda Das, Irene T Weber, Hiroaki Mitsuya
Design, synthesis, and evaluation of a new class of exceptionally potent HIV-1 protease inhibitors are reported. Inhibitor 5 displayed superior antiviral activity and drug-resistance profiles. In fact, this inhibitor showed several orders of magnitude improved antiviral activity over the FDA approved drug darunavir. This inhibitor incorporates an unprecedented 6-5-5 ring-fused crown-like tetrahydropyranofuran as the P2 ligand and an aminobenzothiazole as the P2' ligand with the (R)-hydroxyethylsulfonamide isostere...
April 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28416195/pitavastatin-versus-pravastatin-in-adults-with-hiv-1-infection-and-dyslipidaemia-intrepid-12-week-and-52-week-results-of-a-phase-4-multicentre-randomised-double-blind-superiority-trial
#12
Judith A Aberg, Craig A Sponseller, Douglas J Ward, Vladimir A Kryzhanovski, Stuart E Campbell, Melanie A Thompson
BACKGROUND: People living with HIV-1 infection are at greater risk for cardiovascular disease than seronegative adults. Treatment of dyslipidaemia with statins has been challenging in people with HIV because of an increased potential for drug interactions due to competing cytochrome P450 metabolism between statins and commonly used antiretroviral agents. Neither pitavastatin nor pravastatin depend on cytochrome P450 for primary metabolism. We aimed to assess the safety and efficacy of pitavastatin versus pravastatin in adults with HIV and dyslipidaemia...
April 13, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28407075/once-daily-atazanavir-cobicistat-and-darunavir-cobicistat-exposure-over-72%C3%A2-h-post-dose-in-plasma-urine-and-saliva-contribution-to-drug-pharmacokinetic-knowledge
#13
Emilie R Elliot, Alieu Amara, Nicole Pagani, Laura Else, Graeme Moyle, Alex Schoolmeesters, Chris Higgs, Saye Khoo, Marta Boffito
Background: We investigated the pharmacokinetics (PK) of atazanavir/cobicistat and darunavir/cobicistat once daily over 72 h following drug intake cessation in plasma, saliva and urine. Methods: Healthy volunteers received a fixed-dose combination of 300/150 mg of atazanavir/cobicistat once daily for 10 days, followed by a 10 day washout period and then a fixed-dose combination of 800/150 mg of darunavir/cobicistat once daily for 10 days. Full PK profiles were assessed for each phase for 72 h following day 10 and parameters determined to the last measurable concentration in plasma, saliva and urine by non-compartmental methods...
April 12, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28403798/treating-older-hiv-1-infected-subjects-with-cobicistat-boosted-darunavir-in-a-48-week-phase-3-trial
#14
Kimberley Brown, Brooke Patterson-Browning, Chris Liu, Meera Patel, Lisa Stewart, Richard E Nettles
BACKGROUND: An aging HIV-1-infected population warrants examination of the acceptability of individual antiretroviral regimens. In a previous study of ritonavir-boosted darunavir (ARTEMIS), similar safety/efficacy profiles were observed in younger (≤45 years) and older (>45 years) HIV-1-infected subjects. OBJECTIVE: To evaluate safety and efficacy outcomes in HIV-1-infected younger versus older subjects treated with cobicistat-boosted darunavir. METHOD: In a 48-week, phase 3b, open-label trial, HIV-1-infected adults were administered darunavir 800 mg and cobicistat 150 mg once-daily with 2 nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs)...
April 7, 2017: Reviews on Recent Clinical Trials
https://www.readbyqxmd.com/read/28403052/second-and-third-line-antiretroviral-therapy-for-children-and-adolescents-a-scoping-review
#15
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/28400541/correction-salvage-therapy-or-simplification-of-salvage-regimens-with-dolutegravir-plus-ritonavir-boosted-darunavir-dual-therapy-in-highly-cart-experienced-subjects-an-italian-cohort
#16
Amedeo F Capetti, Gaetana Sterrantino, Maria V Cossu, Giovanni Cenderello, Anna M Cattelan, Giuseppe V De Socio, Stefano Rusconi, Niccolò Riccardi, Gian M Baldin, Serena Cima, Fosca P Niero, Giuliano Rizzardini, Lolita Sasset
No abstract text is available yet for this article.
November 28, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/28399819/comparison-of-atazanavir-ritonavir-and-darunavir-ritonavir-based-antiretroviral-therapy-for-antiretroviral-na%C3%A3-ve-patients
#17
Tony Antoniou, Leah Szadkowski, Sharon Walmsley, Curtis Cooper, Ann N Burchell, Ahmed M Bayoumi, Julio S G Montaner, Mona Loutfy, Marina B Klein, Nima Machouf, Christos Tsoukas, Alexander Wong, Robert S Hogg, Janet Raboud
BACKGROUND: Atazanavir/ritonavir and darunavir/ritonavir are common protease inhibitor-based regimens for treating patients with HIV. Studies comparing these drugs in clinical practice are lacking. METHODS: We conducted a retrospective cohort study of antiretroviral naïve participants in the Canadian Observational Cohort (CANOC) collaboration initiating atazanavir/ritonavir- or darunavir/ritonavir-based treatment. We used separate Fine and Gray competing risk regression models to compare times to regimen failure (composite of virologic failure or discontinuation for any reason)...
April 11, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28398959/emergence-of-untreatable-multidrug-resistant-hiv-1-in-patients-failing-second-line-therapy-in-kenya
#18
Seth C Inzaule, Raph L Hamers, Irene Mukui, Kennedy Were, Prestone Owiti, Daniel Kwaro, Tobias F Rinke de Wit, Clement Zeh
: We performed a countrywide assessment of HIV drug resistance among 123 patients with virological failure on second-line antiretroviral therapy (ART) in Kenya. The percentage of patients harboring intermediate-to-high-level resistance was 27% for lopinavir-ritonavir, 24% for atazanavir-ritonavir and 7% for darunavir-ritonavir, and 25% had complete loss of activity to all available first- and second-line drugs. Overall, one in four patients failing second-line ART have completely exhausted available antiretrovirals in Kenya, highlighting the need for increased access to third-line drugs...
April 10, 2017: AIDS
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
#19
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/28390117/different-cell-cycle-modulation-in-skov-3-ovarian-cancer-cell-line-by-anti-hiv-drugs
#20
Angelica Perna, Angela Lucariello, Carmine Sellitto, Iolanda Agliata, Maria Carleo, Vincenzo Sangiovanni, Vincenzo Esposito, Germano Guerra, Luigi Cobellis, Antonio De Luca
Anti-retroviral drugs used for the treatment of Human Immunodeficiency Virus (HIV) have proven to be effective even against cancer. Drawing from this background the aim of our research project was to evaluate the effects of anti-HIV drugs that belong to the Nucleoside and Nucleotide Reverse Transcriptase Inhibitors (NRTI, abacavir and tenofovir), Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTI, efavirenz and etravirine) and Protease Inhibitors (PI, darunavir) on ovarian adenocarcinoma cell line (Skov-3)...
March 26, 2017: Oncology Research
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