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Etravirine

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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
#1
Shanmugam Saravanan, Bagavathi Kausalya, Selvamurthi Gomathi, Sathasivam Sivamalar, Balakrishnan Pachamuthu, Selvamuthu Poongulali, Ambrose Pradeep, Solomon S 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 a first generation non-nucleoside reverse transcriptase 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 reverse transcriptase inhibitors drugs Etravirine and Rilpivirine, respectively. These cross-resistance mutations may compromise future NNRTI based regimens, especially in resource-limited settings...
November 21, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27788239/interaction-between-darunavir-and-etravirine-is-partly-mediated-by-cyp3a5-polymorphism
#2
Leïla Belkhir, Laure Elens, Francis Zech, Nadtha Panin, Anne Vincent, Jean Cyr Yombi, Bernard Vandercam, Vincent Haufroid
OBJECTIVES: To assess the impact of the loss-of-function CYP3A5*3 allele (rs776746, 6986A>G SNP) on darunavir (DRV) plasma concentrations. METHODS: 135 HIV-1 infected patients treated with DRV-based therapy were included in the study and plasma samples were obtained immediately before drug intake in order to determine DRV trough concentrations using an ultra performance liquid chromatography method (UPLC) with diode-array detection (DAD). Noteworthy is the fact that in 16 (11...
2016: PloS One
https://www.readbyqxmd.com/read/27780535/etravirine-inhibits-abcg2-drug-transporter-and-affects-transplacental-passage-of-tenofovir-disoproxil-fumarate
#3
Josef Reznicek, Martina Ceckova, Lenka Tupova, Frantisek Staud
INTRODUCTION: All HIV positive pregnant women should receive combination antiretroviral therapy (cART) to prevent mother-to-child transmission (MTCT) of the virus. It has recently been shown that fetal exposure of nucleoside reverse transcriptase inhibitors (NRTIs) tenofovir disoproxil fumarate (TDF) and abacavir is decreased by placental ABC transporters p-glycoprotein (ABCB1) and BCRP (ABCG2). The aim of this study was to evaluate transporter-mediated drug-drug interactions (DDI) between etravirine (TMC125), a novel non-nucleoside reverse transcriptase inhibitor used in cART, and the NRTIs and to assess the relevance of such DDI for transplacental pharmacokinetics of TDF and abacavir...
November 2016: Placenta
https://www.readbyqxmd.com/read/27747723/postoperative-bleeding-after-administration-of-a-single-dose-of-rivaroxaban-to-a-patient-receiving-antiretroviral-therapy
#4
Carmela E Corallo, Louise Grannell, Huyen Tran
A 62-year-old man was admitted to hospital for elective revision of a left total hip arthroplasty. His history was significant for human immunodeficiency virus (HIV) infection for which he was taking the following antiretroviral agents (ARVs): etravirine, ritonavir, darunavir, raltegravir and tenofovir/emtricitabine. Rivaroxaban 10 mg daily was commenced on the second postoperative day for venous thromboembolism (VTE) prophylaxis. Approximately 24 h later, the patient developed hypotension and anaemia, accompanied by thigh swelling due to bleeding at the surgical site...
December 2015: Drug Safety—Case Reports
https://www.readbyqxmd.com/read/27746450/therapeutic-drug-monitoring-of-anti-human-immunodeficiency-virus-drugs-in-a-patient-with-short-bowel-syndrome
#5
Motoko Ikuma, Dai Watanabe, Hiroki Yagura, Misa Ashida, Masaaki Takahashi, Masaaki Shibata, Tadafumi Asaoka, Munehiro Yoshino, Tomoko Uehira, Wataru Sugiura, Takuma Shirasaka
An elderly woman with human immunodeficiency virus-1 infection developed short bowel syndrome as a result of extensive intestinal resection. Considering the possibility of poor absorption of antiretroviral drugs (ARVs), therapeutic drug monitoring (TDM) was performed. A single-dose test of 6 ARVs (darunavir, ritonavir, lopinavir, etravirine, maraviroc, and raltegravir) did not provide information on the appropriate ARV, and repeated TDM under continuous antiretroviral therapy resulted in viral suppression below 50 copies/mL, which was considered to be treatment success...
2016: Internal Medicine
https://www.readbyqxmd.com/read/27704010/human-immunodeficiency-virus-1-sequence-changes-and-drug-resistance-mutation-among-virologic-failures-of-lopinavir-ritonavir-monotherapy-aids-clinical-trials-group-protocol-a5230
#6
Saran Vardhanabhuti, David Katzenstein, John Bartlett, Nagalingeswaran Kumarasamy, Carole L Wallis
Background.  The mechanism of virologic failure (VF) of lopinavir/ritonavir (LPV/r) monotherapy is not well understood. We assessed sequence changes in human immunodeficiency virus-1 reverse-transcriptase (RT) and protease (PR) regions. Methods.  Human immunodeficiency virus-1 pol sequences from 34 participants who failed second-line LPV/r monotherapy were obtained at study entry (SE) and VF. Sequence changes were evaluated using phylogenetic analysis and hamming distance. Results.  Human immunodeficiency virus-1 sequence change was higher over drug resistance mutation (DRM) sites (median genetic distance, 2...
September 2016: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/27665573/evaluation-of-concomitant-antiretrovirals-and-cyp2c9-cyp2c19-polymorphisms-on-the-pharmacokinetics-of-etravirine
#7
Bruce Green, Herta Crauwels, Thomas N Kakuda, Simon Vanveggel, Anne Brochot
BACKGROUND: Etravirine is a non-nucleoside reverse transcriptase inhibitor indicated in combination with other antiretrovirals for treatment-experienced HIV patients ≥6 years of age. Etravirine is primarily metabolized by cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A. This analysis determined the impact of concomitant antiretrovirals and CYP2C9/CYP2C19 phenotype on the pharmacokinetics of etravirine. METHODS: We used 4728 plasma concentrations from 817 adult subjects collected from four clinical studies to develop the population pharmacokinetic model...
September 24, 2016: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/27659733/hiv-1-antiretroviral-drug-resistance-patterns-in-patients-failing-nnrti-based-treatment-results-from-a-national-survey-in-south-africa
#8
K Steegen, M Bronze, M A Papathanasopoulos, G van Zyl, D Goedhals, E Variava, W MacLeod, I Sanne, W S Stevens, S Carmona
BACKGROUND: Routine HIV-1 antiretroviral drug resistance testing for patients failing NNRTI-based regimens is not recommended in resource-limited settings. Therefore, surveys are required to monitor resistance profiles in patients failing ART. METHODS: A cross-sectional survey was conducted amongst patients failing NNRTI-based regimens in the public sector throughout South Africa. Virological failure was defined as two consecutive HIV-1 viral load results >1000 RNA copies/mL...
September 22, 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27645512/clinical-and-emotional-factors-related-to-erectile-dysfunction-in-hiv-infected-men
#9
Carmina R Fumaz, Aintzane Ayestaran, Nuria Perez-Alvarez, Jose A Muñoz-Moreno, Maria Jose Ferrer, Eugenia Negredo, Bonaventura Clotet
The prevalence and associated factors of erectile dysfunction (ED) in Human Immunodeficiency Virus (HIV)-infected men remain controversial. The authors evaluated ED, clinical, and emotional variables in a group of 501 HIV-infected men in a cross-sectional 4-month observational study. ED was assessed using the International Index of Erectile Function-5 and emotional status using the Hospital Anxiety and Depression (HAD) questionnaire. Median age (interquartile range) was 42 (35, 48) years. Time since HIV diagnosis was 6...
September 19, 2016: American Journal of Men's Health
https://www.readbyqxmd.com/read/27632783/development-and-validation-of-a-liquid-chromatographic-tandem-mass-spectrometric-method-for-the-multiplexed-quantification-of-etravirine-maraviroc-raltegravir-and-rilpivirine-in-human-plasma-and-tissue
#10
Teresa L Parsons, Mark A Marzinke
BACKGROUND: Analytical methodologies for antiretroviral (ARV) quantification are important in determining both systemic and localized drug concentrations. The CCR5-antagonist maraviroc (MVC), the non-nucleoside reverse transcriptase inhibitors (NNRTIs) etravirine (ETV) and rilpivirine (RPV), as well as the integrase strand transfer inhibitor (INSTI) raltegravir (RAL), have all been evaluated using both oral and non-oral dosing regimens, demonstrating a need for dynamic and sensitive bioanalytical tools for drug quantification in plasma and tissue...
November 30, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27540363/etravirine-pharmacokinetics-in-hiv-infected-pregnant-women
#11
Nikki Mulligan, Stein Schalkwijk, Brookie M Best, Angela Colbers, Jiajia Wang, Edmund V Capparelli, José Moltó, Alice M Stek, Graham Taylor, Elizabeth Smith, Carmen Hidalgo Tenorio, Nahida Chakhtoura, Marjo van Kasteren, Courtney V Fletcher, Mark Mirochnick, David Burger
BACKGROUND: The study goal was to describe etravirine pharmacokinetics during pregnancy and postpartum in HIV-infected women. METHODS: IMPAACT P1026s and PANNA are on-going, non-randomized, open-label, parallel-group, multi-center phase-IV prospective studies in HIV-infected pregnant women. Intensive steady-state 12-h pharmacokinetic profiles were performed from 2nd trimester through postpartum. Etravirine was measured at two labs using validated ultra performance liquid chromatography (detection limits: 0...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27515949/switching-to-boosted-protease-inhibitor-plus-a-second-antiretroviral-drug-dual-therapy-for-treatment-simplification-a-multicenter-observational-study
#12
Alessandra Latini, Massimiliano Fabbiani, Vanni Borghi, Gaetana Sterrantino, Alberto Giannetti, Patrizia Lorenzini, Laura Loiacono, Adriana Ammassari, Rita Bellagamba, Manuela Colafigli, Gabriella D'Ettorre, Simona Di Giambenedetto, Andrea Antinori, Mauro Zaccarelli
BACKGROUND: Aim of the study was to assess predictors of discontinuation/toxicity of boosted PI-based (PI/r) dual therapy (DT). METHODS: Observational, retrospective switch study in patients successfully treated with triple drugs regimen. Patients switched to PI/r based DT [darunavir (DRV/r), lopinavir (LPV/r) or atazanavir (ATV/r)] plus a second drug: [raltegravir (RAL), maraviroc (MVC) etravirine (ETR), lamivudine (3TC) or tenofovir (TDF)] between 2009 and 2014 were included...
2016: BMC Infectious Diseases
https://www.readbyqxmd.com/read/27439522/high-efficacy-of-first-line-art-in-a-west-african-cohort-assessed-by-dried-blood-spot-virological-and-pharmacological-measurements
#13
Pierre de Truchis, Minh Patrick Lê, Mamane Daou, Boubacar Madougou, Yacouba Nouhou, Sahada Moussa Saley, Achirou Sani, Eric Adehossi, Elisabeth Rouveix, Mamadou Saidou, Gilles Peytavin, Constance Delaugerre
OBJECTIVES: The objectives of this study were to determine the rate of viral success in HIV-infected patients on first-line ART by the assessment of dried blood spot (DBS) viral load (VL) and to assess the performance of DBS sampling for VL measurement, genotypic resistance and antiretroviral concentration determinations. METHODS: HIV-infected patients treated for >1 year with first-line ART in Niamey, Niger were included. VL based on nucleic acid sequence-based amplification (NASBA) assay (limit of quantification <800 copies/mL) was measured on DBS capillary samples...
November 2016: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/27376653/drug-interactions-between-antiretrovirals-and-drugs-used-to-treat-benign-prostatic-hyperplasia-lower-urinary-tract-symptoms
#14
Denise Kreutzwiser, Alice Tseng
INTRODUCTION: Significant advances in antiretroviral (ARV) therapy have transformed HIV into a chronic manageable disease. Co-morbidities associated with aging, such as benign prostatic hyperplasia (BPH), are becoming increasingly prevalent in the HIV-infected population. The pharmacological treatment of BPH involves medications mainly metabolized by CYP 450 enzymes, while many ARVs have inducing or inhibiting effects on the CYP 450 system. Consequently, there is potential for significant pharmacokinetic (PK) interactions between these two classes of medications...
October 2016: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/27367009/effectiveness-of-etravirine-based-therapy-for-treatment-experienced-hiv-infected-patients
#15
Gloria Huerta García, José Antonio Mata-Marín, Juan Carlos Domínguez-Hermosillo, Marcelino Chavez-García, Marco Issac Banda-Lara, Nohemi Nuñez-Rodríguez, Javier Enrique Cruz-Herrera, Jorge Luis Sandoval-Ramírez, Alfredo Villagómez-Ruiz, Bulmaro Manjarrez-Tellez, Jesús Enrique Gaytan-Martínez
INTRODUCTION: Treatment options are limited for HIV-1-infected individuals who have received extensive previous antiretroviral therapy. ETV has shown significant clinical benefits in treatment-experienced HIV-1+ patients with antiretroviral resistance. The aim of this study was to evaluate the effectiveness of ETV plus optimized background regimen in real-life conditions in a cohort of highly HIV-1 antiretroviral-experienced patients. METHODOLOGY: Retrospective cohort of treatment-experienced HIV-1-infected adults with virological failure who started therapy with an ETV-containing regimen...
2016: Journal of Infection in Developing Countries
https://www.readbyqxmd.com/read/27346600/antiretroviral-resistance-after-first-line-antiretroviral-therapy-failure-in-diverse-hiv-1-subtypes-in-the-second-line-study
#16
Edward P Lam, Cecilia L Moore, Eduardo Gotuzzo, Chidi Nwizu, Adeeba Kamarulzaman, Ploenchan Chetchotisakd, Jean van Wyk, Hedy Teppler, Nagalingeswaran Kumarasamy, Jean-Michel Molina, Sean Emery, David A Cooper, Mark A Boyd
We investigate mutations and correlates according to HIV-1 subtype after virological failure (VF) of standard first-line antiretroviral therapy (ART) (non-nucleoside/nucleotide reverse transcriptase inhibitor [NNRTI] +2 nucleoside/nucleotide reverse transcriptase inhibitor [N(t)RTI]). SECOND-LINE study participants were assessed at baseline for HIV-1 subtype, demographics, HIV-1 history, ART exposure, viral load (VL), CD4(+) count, and genotypic ART resistance. We used backward stepwise multivariate regression (MVR) to assess associations between baseline variables and presence of ≥3 N(t)RTI mutations, ≥1 NNRTI mutation, ≥3 thymidine analog-N(t)RTI [ta-N(t)RTI] mutations (TAMs), the K65/K70 mutation, and predicted etravirine (ETV)/rilpivirine (RPV) activity...
September 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27318755/etravirine-as-a-culprit-of-recurrent-drug-eluting-in-stent-restenosis-in-an-hiv-patient
#17
Gaurav K Sharma, Michael Megaly
No abstract text is available yet for this article.
September 15, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27291892/extensive-variation-in-drug-resistance-mutational-profile-of-brazilian-patients-failing-antiretroviral-therapy-in-five-large-brazilian-cities
#18
Carlos Brites, Lauro Pinto-Neto, Melissa Medeiros, Estevão Nunes, Eduardo Sprinz, Mariana Carvalho
BACKGROUND: Development of drug-resistance mutations is the main cause of failure in antiretroviral therapy. In Brazil, there is scarce information on resistance pattern for patients failing antiretroviral therapy. OBJECTIVES: To define the HIV mutational profile associated with drug resistance in Brazilian patients from 5 large cities, after first, second or further failures to antiretroviral therapy. METHODS: We reviewed genotyping results of 1520 patients failing therapy in five Brazilian cities...
July 2016: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27267005/structural-optimization-of-pyridine-type-dapy-derivatives-to-exploit-the-tolerant-regions-of-the-nnrti-binding-pocket
#19
Wenmin Chen, Peng Zhan, Dirk Daelemans, Jiapei Yang, Boshi Huang, Erik De Clercq, Christophe Pannecouque, Xinyong Liu
Based on the crystallographic studies of diarylpyrimidines (DAPYs), we embarked on incorporating the hydrophilic piperidyl or morpholinyl group into the known DAPY derivatives bearing the pyridine moiety as a core structure, with the double aim to exploit additional interactions with the HIV-1 NNRTI binding pocket (NNIBP), as well as to improve the compound solubility. The antiviral evaluation result show that the most potent compounds I-8b2, I-8b3, I-8b4 and I-8c3 exhibited anti-HIV-1 (IIIB) strain activity ranging from 7...
October 4, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27236000/simultaneous-measurement-of-etravirine-maraviroc-and-raltegravir-in-pigtail-macaque-plasma-vaginal-secretions-and-vaginal-tissue-using-a-lc-ms-ms-assay
#20
Anna K Blakney, Yonghou Jiang, Dale Whittington, Kim A Woodrow
Etravirine (ETR), maraviroc (MVC) and raltegravir (RAL) are promising antiretroviral drugs being used in HIV treatment and may be interesting for prevention applications such as oral or topical pre-exposure prophylaxis. Here we describe a sensitive and accurate method for the simultaneous detection of ETR, MVC and RAL from pigtail macaque plasma, vaginal secretions, and vaginal tissue. This method is characterized by a straightforward precipitation extraction method, a limit of quantification <0.5ngmL(-1) for all three antiretrovirals bolstered by a corresponding internal standard for each drug analyte, and short run time...
July 1, 2016: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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