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https://www.readbyqxmd.com/read/28222098/multicenter-study-of-skin-rashes-and-hepatotoxicity-in-antiretroviral-na%C3%A3-ve-hiv-positive-patients-receiving-non-nucleoside-reverse-transcriptase-inhibitor-plus-nucleoside-reverse-transcriptase-inhibitors-in-taiwan
#1
Pei-Ying Wu, Chien-Yu Cheng, Chun-Eng Liu, Yi-Chien Lee, Chia-Jui Yang, Mao-Song Tsai, Shu-Hsing Cheng, Shih-Ping Lin, De-Yu Lin, Ning-Chi Wang, Yi-Chieh Lee, Hsin-Yun Sun, Hung-Jen Tang, Chien-Ching Hung
OBJECTIVES: Two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs) plus 1 non-NRTI (nNRTI) remain the preferred or alternative combination antiretroviral therapy (cART) for antiretroviral-naive HIV-positive patients in Taiwan. The three most commonly used nNRTIs are nevirapine (NVP), efavirenz (EFV) and rilpivirine (RPV). This study aimed to determine the incidences of hepatotoxicity and skin rashes within 4 weeks of initiation of cART containing 1 nNRTI plus 2 NRTIs. METHODS: Between June, 2012 and November, 2015, all antiretroviral-naive HIV-positive adult patients initiating nNRTI-containing cART at 8 designated hospitals for HIV care were included in this retrospective observational study...
2017: PloS One
https://www.readbyqxmd.com/read/28219799/uplc-ms-ms-method-for-the-simultaneous-quantification-of-three-new-antiretroviral-drugs-dolutegravir-elvitegravir-and-rilpivirine-and-other-thirteen-antiretroviral-agents-plus-cobicistat-and-ritonavir-boosters-in-human-plasma
#2
Marco Simiele, Alessandra Ariaudo, Amedeo De Nicolò, Fabio Favata, Martina Ferrante, Chiara Carcieri, Stefano Bonora, Giovanni Di Perri, Antonio De Avolio
Rilpivirine (RPV), dolutegravir (DTG) and elvitegravir (EVG) are the latest antiretroviral drugs approved for treatment of HIV infection. Currently, poor information is currently available concerning their pharmacokinetic and pharmacodynamic properties, thus making the use of therapeutic drug monitoring for these drugs not useful. This lack of information is partially due to the absence of an high-throughput method for their simultaneous quantification together with other antiretroviral drugs. In this work, we describe the development and validation of a new UPLC-MS/MS method to quantify these drugs, together with other fourteen antiretroviral agents, in human plasma...
February 3, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28207816/hiv-drug-therapy-duration-a-swedish-real-world-nationwide-cohort-study-on-infcarehiv-2009-2014
#3
Amanda Häggblom, Stefan Lindbäck, Magnus Gisslén, Leo Flamholc, Bo Hejdeman, Andreas Palmborg, Amy Leval, Eva Herweijer, Sverrir Valgardsson, Veronica Svedhem
BACKGROUND: As HIV infection needs a lifelong treatment, studying drug therapy duration and factors influencing treatment durability is crucial. The Swedish database InfCareHIV includes high quality data from more than 99% of all patients diagnosed with HIV infection in Sweden and provides a unique opportunity to examine outcomes in a nationwide real world cohort. METHODS: Adult patients who started a new therapy defined as a new 3rd agent (all antiretrovirals that are not N[t]RTIs) 2009-2014 with more than 100 observations in treatment-naive or treatment-experienced patients were included...
2017: PloS One
https://www.readbyqxmd.com/read/28198203/enteral-administration-of-twice-daily-dolutegravir-and-rilpivirine-as-a-part-of-a-triple-therapy-regimen-in-a-critically-ill-patient-with-hiv
#4
Sarah Lynn Turley, Patricia Pecora Fulco
The administration of antiretroviral therapy (ART) in intubated critically ill patients may be challenging. Limited pharmacokinetic data exist characterizing the effects of crushed ART with subsequent enteral administration on antiretroviral drug concentrations or the clinical impact on HIV virologic suppression. We report a case of a 27-year-old HIV-positive male with presumed multidrug-resistant HIV and a diagnosis of lymphoma who required enteral ART administration after intensive care unit admission. Crushed twice-daily dolutegravir (separated from enteral nutrition by 2 hours) and rilpivirine (concurrently with a bolus feed) were administered via an orogastric tube...
January 1, 2017: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/28182783/correction-abacavir-lamivudine-plus-rilpivirine-is-an-effective-and-safe-strategy-for-hiv-1-suppressed-patients-48-week-results-of-the-simriki-retrospective-study
#5
Jesús Troya, Pablo Ryan, Esteban Ribera, Daniel Podzamczer, Victor Hontañón, Jose Alberto Terrón, Vicente Boix, Santiago Moreno, Pilar Barrufet, Manuel Castaño, Ana Carrero, María José Galindo, Ignacio Suárez-Lozano, Hernando Knobel, Miguel Raffo, Javier Solís, María Yllescas, Herminia Esteban, Juan González-García, Juan Berenguer, Arkaitz Imaz
[This corrects the article DOI: 10.1371/journal.pone.0164455.].
2017: PloS One
https://www.readbyqxmd.com/read/28160944/dihydropyrimidinone-isatin-hybrids-as-novel-non-nucleoside-hiv-1-reverse-transcriptase-inhibitors
#6
Titiksh L Devale, Jignesh Parikh, Pankaj Miniyar, Pankaj Sharma, Birendra Shrivastava, Prashant Murumkar
A novel series of substituted N-(2-(2,3-dioxoindolin-1-yl)acetyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxamide was designed, synthesized and evaluated for in vitro Reverse Transcriptase (RT) inhibitory activity. This series is a combination of peculiar structural features from leading scaffolds of [(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and oxyindole. In vitro screening led to identification of two hybrids (9c and 9d) possessing higher RT inhibitory activity than the standard rilpivirine...
January 18, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28151023/emtricitabine-tenofovir-alafenamide-for-the-treatment-of-hiv
#7
Katya C Corado, Eric S Daar
Tenofovir alafenamide is a new oral prodrug of tenofovir resulting in relatively low plasma levels and rapid uptake into peripheral blood mononuclear cells in its active form. The United States Food and Drug Administration has now approved this drug coformulated with elvitegravir/cobicistat/emtricitabine, rilpivirine/emtricitabine and emtricitabine. United States guidelines now list this formulation as one of the preferred components of a variety of antiretroviral regimens, and is included as an alternative in other international guidelines, with the notable exception of the World Health Organization, mostly due to limited availability...
February 2, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28143756/real-world-persistence-with-antiretroviral-therapy-for-hiv-in-the-united-kingdom-a-multicentre-retrospective-cohort-study
#8
Joseph M Lewis, Colette Smith, Adele Torkington, Craig Davies, Shazaad Ahmad, Andrew Tomkins, Jonathan Shaw, Margaret Kingston, Ghadeer Muqbill, Philip Hay, Larissa Mulka, Deborah Williams, Laura Waters, Nataliya Brima, Neal Marshall, Margaret Johnson, Mas Chaponda, Mark Nelson
OBJECTIVES: Persistence with an antiretroviral therapy (ART) regimen for HIV can be defined as the length of time a patient remains on therapy before stopping or switching. We aimed to describe ART persistence in treatment naïve patients starting therapy in the United Kingdom, and to describe differential persistence by treatment regimen. METHODS: We performed a retrospective cohort study at eight UK centres of ART-naïve adults commencing ART between 2012 and 2015...
January 29, 2017: Journal of Infection
https://www.readbyqxmd.com/read/28129253/hiv-drug-resistance-mutations-in-non-b-subtypes-after-prolonged-virological-failure-on-nnrti-based-first-line-regimens-in-sub-saharan-africa
#9
Cissy Kityo, Jennifer Thompson, Immaculate Nankya, Anne Hoppe, Emmanuel Ndashimye, Colin Warambwa, Ivan Mambule, Joep J van Oosterhout, Kara Wools-Kaloustian, Silvia Bertagnolio, Philippa J Easterbrook, Peter Mugyenyi, A Sarah Walker, Nicholas Paton
OBJECTIVE: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing non-nucleoside-reverse-transcriptase-inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) regimens in programmes without routine viral load (VL) monitoring and to examine inter-subtype differences in DRMs. DESIGN: Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, Malawi were analysed...
January 25, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28112280/tenofovir-alafenamide-fumarate-for-the-treatment-of-hiv-infection
#10
R Sampath, J Zeuli, S Rizza, Z Temesgen
Tenofovir alafenamide fumarate is a recently developed prodrug of tenofovir, a nucleotide analogue reverse transcriptase inhibitor with potent inhibitory activity against HIV. The utility of a previously developed tenofovir prodrug, tenofovir disoproxil fumarate, had been hampered by renal and bone mineral adverse events. Tenofovir alafenamide fumarate overcomes the shortcomings of tenofovir disoproxil fumarate by delivering high intracellular concentrations of the parent drug, tenofovir, while substantially reducing systemic exposure...
November 2016: Drugs of Today
https://www.readbyqxmd.com/read/28091393/viral-blips-were-infrequent-in-treatment-naive-adults-treated-with-rilpivirine-emtricitabine-tenofovir-df-or-efavirenz-emtricitabine-tenofovir-df-through-96-weeks
#11
Danielle P Porter, Rima Kulkarni, Will Garner, Michael D Miller, Kirsten L White
BACKGROUND: The clinical impact of transient episodes of HIV viremia (viral blips) on virologic failure and resistance development is not fully understood. Here we investigated the blip frequency and virologic outcomes of HIV-1-infected subjects experiencing viral blips among treatment-naïve subjects initiating therapy on rilpivirine (RPV)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF through 96 weeks of treatment. METHODS: Subjects treated with at least one dose of study drug and with at least one post-baseline HIV-1 RNA value were included in this analysis...
January 16, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28034359/hiv-1-drug-susceptibility-to-potential-second-and-third-line-antiretroviral-regimens-among-cameroonian-patients-evidence-from-a-cross-sectional-design
#12
Aubin J Nanfack, Desire Takou, Joseph Fokam, Romina Salpini, Maria M Santoro, Giulia Cappelli, Martin Baane, Suzie M Tetang, Josef Eberle, Lutz Gürtler, Francesca Ceccherini-Silberstein, Judith N Torimiro, Vittorio Colizzi, Carlo-Federico Perno, Alexis Ndjolo
BACKGROUND: Scale-up of antiretroviral therapy (ART) and the growing number of long-term treated patients may favor multi-HIV drug resistance (HIVDR) in resource-limited settings. Understanding the burden of HIVDR with ART-exposure may provide new insights for an effective long-term management of infected patients. METHODS: Sixty-six HIV-infected individuals (18 ART-naïve, 24 failing first-line, 24 failing second-line ART) living in Yaoundé-Cameroon were evaluated by sequencing protease-reverse transcriptase (PR-RT, n=62), envelope-V3 loop (V3, n=58) and integrase (IN, n=30) regions...
December 29, 2016: Current HIV Research
https://www.readbyqxmd.com/read/28008980/antiretroviral-treatment-with-efavirenz-disrupts-the-blood-brain-barrier-integrity-and-increases-stroke-severity
#13
Luc Bertrand, Levi Dygert, Michal Toborek
The introduction of antiretroviral drugs (ARVd) changed the prognosis of HIV infection from a deadly disease to a chronic disease. However, even with undetectable viral loads, patients still develop a wide range of pathologies, including cerebrovascular complications and stroke. It is hypothesized that toxic side effects of ARVd may contribute to these effects. To address this notion, we evaluated the impact of several non-nucleoside reverse transcriptase inhibitors (NNRTI; Efavirenz, Etravirine, Rilpivirine and Nevirapine) on the integrity of the blood-brain barrier, and their impact on severity of stroke...
December 23, 2016: Scientific Reports
https://www.readbyqxmd.com/read/28008867/dolutegravir-plasma-concentrations-according-to-companion-antiretroviral-drug-unwanted-drug-interaction-or-desirable-boosting-effect
#14
Dario Cattaneo, Davide Minisci, Valeria Cozzi, Agostino Riva, Paola Meraviglia, Emilio Clementi, Massimo Galli, Cristina Gervasoni
BACKGROUND: Studies in healthy volunteers have shown that the recently approved HIV integrase inhibitor dolutegravir has limited drug-to-drug interaction profile. Here we carried out a pharmacokinetic survey in HIV-infected patients given dolutegravir as part of their antiretroviral therapy. METHODS: Dolutegravir plasma trough concentrations were measured in 78 HIV infected patients given the drug in combination with a protease inhibitor, a non nucleoside reverse transcriptase inhibitor or abacavir/lamivudine...
December 23, 2016: Antiviral Therapy
https://www.readbyqxmd.com/read/27999048/pre-existent-nrti-and-nnrti-resistance-impacts-on-maintenance-of-virological-suppression-in-hiv-1-infected-patients-who-switch-to-a-tenofovir-emtricitabine-rilpivirine-single-tablet-regimen
#15
D Armenia, D Di Carlo, A Calcagno, G Vendemiati, F Forbici, A Bertoli, G Berno, S Carta, F Continenza, V Fedele, R Bellagamba, S Cicalini, A Ammassari, R Libertone, M Zaccarelli, V Ghisetti, M Andreoni, F Ceccherini-Silberstein, S Bonora, G Di Perri, A Antinori, C F Perno, M M Santoro
OBJECTIVES: To evaluate the maintenance of virological suppression (VS) in antiretroviral-treated HIV-1-suppressed patients switching to a tenofovir/emtricitabine/rilpivirine (TDF/FTC/RPV) single-tablet regimen, by considering pre-existent resistance (pRes). METHODS: pRes was evaluated according to resistance on all previous plasma genotypic resistance tests. Probability and predictors of virological rebound (VR) were evaluated. RESULTS: Three hundred and nine patients were analysed; 5...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27999010/pharmacokinetics-of-dolutegravir-and-rilpivirine-in-combination-with-simeprevir-and-sofosbuvir-in-hiv-hepatitis-c-virus-coinfected-patients-with-liver-cirrhosis
#16
Marco Merli, Laura Galli, Letizia Marinaro, Alessandra Ariaudo, Emanuela Messina, Caterina Uberti-Foppa, Antonella Castagna, Antonio D'Avolio, Adriano Lazzarin, Stefano Bonora, Hamid Hasson
OBJECTIVES: To evaluate the plasma trough concentrations (Ctrough) of dolutegravir and rilpivirine used in combination with simeprevir and sofosbuvir in HIV/hepatitis C virus (HCV)-coinfected patients with liver cirrhosis. Virological efficacy and safety of both ART and anti-HCV therapy were assessed. PATIENTS AND METHODS: A prospective observational study in HIV/HCV-coinfected patients with liver cirrhosis on ART with dolutegravir plus rilpivirine and treated with simeprevir plus sofosbuvir (±ribavirin) was conducted...
December 20, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27993846/nonnucleoside-reverse-transcriptase-inhibitors-reduce-hiv-1-virus-production-from-latently-infected-resting-cd4-t-cells-following-latency-reversal
#17
Jennifer M Zerbato, Gilda Tachedjian, Nicolas Sluis-Cremer
Therapeutic strategies that target the latent HIV-1 reservoir in resting CD4+ T cells of infected-individuals are always administered in the presence of combination antiretroviral therapy. Using a primary cell of HIV-1 latency, we evaluated whether different antiviral drug classes affected latency reversal (as assessed by extracellular virus production) by anti-CD3/CD28 monoclonal antibodies or by bryostatin 1. We found that the nonnucleoside reverse transcriptase inhibitors efavirenz and rilpivirine significantly decreased HIV-1 production by ≥ 1 log...
December 19, 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27941989/real-world-assessment-of-renal-and-bone-safety-among-patients-with-hiv-infection-exposed-to-tenofovir-disoproxil-fumarate-containing-single-tablet-regimens
#18
Ella T Nkhoma, Lisa Rosenblatt, Joel Myers, Angelina Villasis-Keever, John Coumbis
OBJECTIVES: Tenofovir disoproxil fumarate (TDF)-containing antiretroviral regimens have been associated with an increased incidence of renal and bone adverse outcomes. Here, we estimated the real-world incidence of renal and bone adverse outcomes among patients with HIV infection receiving different TDF-containing single-tablet regimens (STRs). METHODS: This cohort study used US health insurance data spanning the years 2008-2014. We identified HIV-infected patients aged ≥18 years (all HIV patients) and those with ≥6 months of continuous enrollment prior to initiating efavirenz/emtricitabine/TDF (EFV/FTC/TDF), rilpivirine/FTC/TDF (RPV/FTC/TDF) or elvitegravir/cobicistat/FTC/TDF (EVG/COBI/FTC/TDF)...
2016: PloS One
https://www.readbyqxmd.com/read/27869478/etravirine-and-rilpivirine-drug-resistance-among-hiv-1-subtype-c-infected-children-failing-non-nucleoside-reverse-transcriptase-inhibitor-based-regimens-in-south-india
#19
Shanmugam Saravanan, Bagavathi Kausalya, Selvamurthi Gomathi, Sathasivam Sivamalar, Balakrishnan Pachamuthu, Poongulali Selvamuthu, Amrose Pradeep, Solomon Sunil, Sarvode N Mothi, Davey M Smith, Rami Kantor
We have analyzed reverse transcriptase (RT) region of HIV-1 pol gene from 97 HIV-infected children who were identified as failing first-line therapy that included first-generation non-nucleoside RT inhibitors (Nevirapine and Efavirenz) for at least 6 months. We found that 54% and 65% of the children had genotypically predicted resistance to second-generation non-nucleoside RT inhibitors drugs Etravirine (ETR) and Rilpivirine, respectively. These cross-resistance mutations may compromise future NNRTI-based regimens, especially in resource-limited settings...
December 23, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27799824/profile-of-cabotegravir-and-its-potential-in-the-treatment-and-prevention-of-hiv-1-infection-evidence-to-date
#20
REVIEW
Thomas Whitfield, Adele Torkington, Clare van Halsema
Modern antiretroviral therapy has demonstrated effectiveness in preexposure prophylaxis (PrEP) and treatment of HIV infection. There is a demand for prevention and treatment regimens that could overcome challenges of improving adherence, toxicity, and dosing convenience. Cabotegravir is an integrase strand transfer inhibitor and an analog of dolutegravir. Unlike dolutegravir, cabotegravir has a long half-life and can be formulated into a long-acting nanosuspension for parenteral administration. Initial pharmokinetic studies in humans have demonstrated adequate drug levels with intramuscular (IM) administration at 4 weekly and 8 weekly intervals, with few interactions with commonly used concomitant medications...
2016: HIV/AIDS: Research and Palliative Care
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