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https://www.readbyqxmd.com/read/28427498/plasma-and-saliva-concentrations-of-abacavir-tenofovir-darunavir-and-raltegravir-in-hiv-1-infected-patients%C3%A2
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
https://www.readbyqxmd.com/read/28384599/the-effect-of-veno-venous-ecmo-on-the-pharmacokinetics-of-ritonavir-darunavir-tenofovir-and-lamivudine
#13
Mohamed A Ghazi Suliman, Kayode Ogungbenro, Christos Kosmidis, Alan Ashworth, Julian Barker, Anita Szabo-Barnes, Andrew Davies, Lee Feddy, Igor Fedor, Tim Hayes, Sarah Stirling, Ignacio Malagon
INTRODUCTION: To our knowledge, there is no published data on the pharmacokinetic (PK) profile of antiretroviral (ART) drugs on patients undergoing extracorporeal membrane oxygenation (ECMO) therapy. We present PK analyses of Ritonavir, Darunavir, Lamivudine and Tenofovir in a patient with HIV who required veno-venous ECMO (VV ECMO). METHODS: Plasma concentrations for Ritonavir, Darunavir, Tenofovir and Lamivudine were obtained while the patient was on ECMO following pre-emptive dose adjustments...
March 12, 2017: Journal of Critical Care
https://www.readbyqxmd.com/read/28382208/etravirine-combined-with-antiretrovirals-other-than-darunavir-ritonavir-for-hiv-1-infected-treatment-experienced-adults-week-48-results-of-a-phase-iv-trial
#14
Eduardo Arathoon, Asad Bhorat, Rodica Silaghi, Herta Crauwels, Ludo Lavreys, Lotke Tambuyzer, Ben Van Baelen, Simon Vanveggel, Magda Opsomer
OBJECTIVE: VIOLIN (TMC125IFD3002; NCT01422330) evaluated the safety, tolerability, and pharmacokinetics of etravirine with antiretrovirals other than darunavir/ritonavir in HIV-1-infected patients. METHODS: In a 48-week, phase IV, single-arm, multicenter study, patients on prior antiretroviral therapy (⩾8 weeks) who needed to change regimen for virologic failure (viral load ⩾ 500 copies/mL) or simplification/adverse events (viral load < 50 copies/mL) received etravirine 200 mg bid with ⩾1 other active antiretroviral, excluding darunavir/ritonavir or only nucleoside/tide reverse transcriptase inhibitors...
2017: SAGE Open Medicine
https://www.readbyqxmd.com/read/28369542/variable-endothelial-cell-function-restoration-after-initiation-of-two-antiretroviral-regimens-in-hiv-infected-individuals
#15
P Echeverría, E Gómez-Mora, S Roura, A Bonjoch, J Puig, N Pérez-Alvarez, A Bayés-Genís, B Clotet, J Blanco, E Negredo
Background: The effect of ART on endothelial cell function is incompletely characterized. Methods: We performed a 24 week prospective, case-control and comparative pilot study of ART-naive HIV-infected patients who started a darunavir- or rilpivirine-based regimen, matched with non-HIV-infected volunteers, to compare changes at week 24 from baseline in levels of circulating endothelial cells (CECs), endothelial progenitor cells (EPCs) and circulating angiogenic cells, as well as changes in immune-activation markers...
March 22, 2017: Journal of Antimicrobial Chemotherapy
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
#16
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/28361290/efficacy-and-safety-of-atazanavir-ritonavir-based-antiretroviral-therapy-for-hiv-1-infected-subjects-a-systematic-review-and-meta-analysis
#17
REVIEW
Amr Menshawy, Ammar Ismail, Abdelrahman Ibrahim Abushouk, Hussien Ahmed, Esraa Menshawy, Ahmed Elmaraezy, Mohamed Gadelkarim, Mohamed Abdel-Maboud, Attia Attia, Ahmed Negida
Atazanavir (ATZ) is a well-tolerated protease inhibitor that can be boosted with ritonavir (r) to treat infection with resistant strains of human immunodeficiency virus 1 (HIV-1). The aim of this meta-analysis was to compare the efficacy, safety, and metabolic effects of ATZ/r regimen versus commonly used antiretroviral drugs such as lopinavir (LPV) and darunavir (DRV) in HIV-1-infected patients. We searched PubMed, Scopus, Embase and Cochrane CENTRAL, using relevant keywords. Data were extracted from eligible randomized trials and pooled as risk ratios (RR) or standardized mean differences (SMD) in a meta-analysis model using RevMan software...
March 30, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28358514/interdependence-of-inhibitor-recognition-in-hiv-1-protease
#18
Janet L Paulsen, Florian Leidner, Debra A Ragland, Nese Kurt Yilmaz, Celia A Schiffer
Molecular recognition is a highly interdependent process. Subsite couplings within the active site of proteases are most often revealed through conditional amino acid preferences in substrate recognition. However, the potential effect of these couplings on inhibition and thus inhibitor design is largely unexplored. The present study examines the interdependency of subsites in HIV-1 protease using a focused library of protease inhibitors, to aid in future inhibitor design. Previously a series of darunavir (DRV) analogs was designed to systematically probe the S1' and S2' subsites...
April 11, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28350802/impact-of-lopinavir-ritonavir-exposure-in-hiv-1-infected-children-and-adolescents-in-madrid-spain-during-2000-2014
#19
Patricia Rojas Sánchez, Luis Prieto, Santiago Jiménez De Ory, Elisa Fernández Cooke, Maria Luisa Navarro, José Tomas Ramos, África Holguín
BACKGROUND: The most-used protease-inhibitor in children is Lopinavir-ritonavir (LPV/r), which provides durable suppression of viral load and increases CD4+T-counts. This study describes the virological outcome of the HIV-1-infected paediatric population exposed to LPV/r during 15 years in Spain. METHODOLOGY: Patients from the Madrid Cohort of HIV-1-infected-children and adolescents exposed to LPV/r as different line therapy during 2000-2014 were selected. The baseline epidemiological-clinical features, viral suppression, changes in CD4+T-CD8+T cell counts and drug susceptibility were recorded before and during LPV/r exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28350300/impact-of-ccr5-integrase-and-protease-inhibitors-on-human-endothelial-cell-function-stress-inflammation-and-senescence
#20
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
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