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https://www.readbyqxmd.com/read/29771694/fostemsavir-a-new-cd4-attachment-inhibitor
#1
Pedro Cahn, Valeria Fink, Patricia Patterson
PURPOSE OF REVIEW: Even in the era of modern HAART, antiretroviral (ARV) failure and emergence of drug resistance is still a problem worldwide. New classes with different mechanisms of action are needed to overcome this challenge. After the integrase inhibitors were launched, more than a decade ago, no new classes were added to the ARV armamentarium. RECENT FINDINGS: Fostemsavir (FTR) is an attachment inhibitor, active regardless of viral tropism, without cross-resistance to any of the existing ARV compounds...
May 15, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29769116/efficacies-of-cabotegravir-and-bictegravir-against-drug-resistant-hiv-1-integrase-mutants
#2
Steven J Smith, Xue Zhi Zhao, Terrence R Burke, Stephen H Hughes
BACKGROUND: Integrase strand transfer inhibitors (INSTIs) are the class of antiretroviral (ARV) drugs most recently approved by the FDA for the treatment of HIV-1 infections. INSTIs block the strand transfer reaction catalyzed by HIV-1 integrase (IN) and have been shown to potently inhibit infection by wild-type HIV-1. Of the three current FDA-approved INSTIs, Dolutegravir (DTG), has been the most effective, in part because treatment does not readily select for resistant mutants. However, recent studies showed that when INSTI-experienced patients are put on a DTG-salvage therapy, they have reduced response rates...
May 16, 2018: Retrovirology
https://www.readbyqxmd.com/read/29764864/targeting-the-hsp40-hsp70-chaperone-axis-as-a-novel-strategy-to-treat-castration-resistant-prostate-cancer
#3
Michael A Moses, Yeong Sang Kim, Genesis M Rivera-Marquez, Nobu Oshima, Matthew J Watson, Kristin Beebe, Catherine Wells, Sunmin Lee, Abbey D Zuehlke, Hao Shao, William E Bingman, Vineet Kumar, Sanjay Malhotra, Nancy L Weigel, Jason E Gestwicki, Jane Trepel, Leonard M Neckers
Castration-resistant prostate cancer (CRPC) is characterized by reactivation of androgen receptor (AR) signaling in part by elevated expression of AR splice variants (ARv) including ARv7, a constitutively active, ligand binding domain (LBD)-deficient variant whose expression has been correlated with therapeutic resistance and poor prognosis. In a screen to identify small molecule dual inhibitors of both androgen-dependent and androgen-independent AR gene signatures, we identified the chalcone C86. Binding studies using purified proteins and CRPC cell lysates revealed C86 to interact with heat shock protein 40 (Hsp40)...
May 15, 2018: Cancer Research
https://www.readbyqxmd.com/read/29756415/the-expression-of-androgen-receptor-and-its-variants-in-human-prostate-cancer-tissue-according-to-disease-status-and-its-prognostic-significance
#4
Sung Woo Park, Jung Hee Kim, Hyun Jung Lee, Dong Hoon Shin, Sang Don Lee, Sik Yoon
PURPOSE: To evaluate changes in the expression of androgen receptor (AR) and its variants (ARVs) in human prostate cancer (PCa) tissues according to disease status, and its prognostic significance following radical prostatectomy (RP). MATERIALS AND METHODS: A total of 282 PCa cases were evaluated, which included 252 localized PCa, 8 metastatic castration resistant prostate cancer (CRPC), and 22 benign prostatic hyperplasia (BPH) cases. Samples were collected from patients who underwent RP or transurethral resection and were stored in ethically approved tissue banks...
April 16, 2018: World Journal of Men's Health
https://www.readbyqxmd.com/read/29742276/hla-b57-01-shields-people-living-with-hiv-for-significantly-better-periodontal-health
#5
Gundolf Schuettfort, Philipp Leuw, Annette Haberl, Eva Herrmann, Kyu-Hyun Park, Timo Wolf, Christoph Stephan
OBJECTIVES: To assess the association between HLA-B57.01 (Human leukocyte antigen) and clinical parameters of chronic periodontitis in people living with HIV (PLWHIV). MATERIALS AND METHODS: All patients were recruited from the HIVCENTER at the Universityhospital Frankfurt during April 2014 and July 2015. Periodontal examination included Periodontal Screening Index (PSI), Gingivalindex (GI), Bleeding on Probing Index (BOP), Periodontal Probing Depth (PD), Clinical Attachment Level (CAL) and DMF-T Score (decayed, missing, filled teeth)...
May 9, 2018: Journal of Periodontology
https://www.readbyqxmd.com/read/29684534/towards-a-maraviroc-long-acting-injectable-nanoformulation
#6
Lee M Tatham, Alison C Savage, Andrew Dwyer, Marco Siccardi, Trevor Scott, Manoli Vourvahis, Andrew Clark, Steven P Rannard, Andrew Owen
Suboptimal adherence to antiretroviral (ARV) therapy can lead to insufficient drug exposure leading to viral rebound and increased likelihood of resistance. This has driven the development of long-acting injectable (LAI) formulations which may mitigate some of these problems. Maraviroc (MVC) is an orally dosed CCR5 antagonist approved for use in patients infected with CCR5-trophic HIV-1. MVC prevents viral entry into host cells, is readily distributed to biologically relevant tissues and has an alternative resistance profile compared to more commonly used therapies...
April 20, 2018: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/29649076/pharmacokinetics-of-tenofovir-alafenamide-when-co-administered-with-other-hiv-antiretrovirals
#7
Rebecca Begley, Moupali Das, Lijie Zhong, John Ling, Brian P Kearney, Joseph M Custodio
BACKGROUND: Tenofovir alafenamide (TAF), a prodrug of the nucleotide analogue tenofovir (TFV), is an antiretroviral (ARV) agent approved either as a complete regimen (elvitegravir/cobicistat/emtricitabine (F)/tenofovir alafenamide (TAF), rilpivirine/F/TAF, bictegravir/F/TAF), or for use with other ARVs (F/TAF), for treatment of HIV. TAF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters. Disposition of TAF may be altered by co-medications that can inhibit or induce P-gp or BCRP transporters...
April 10, 2018: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/29607652/stable-caloric-intake-and-continued-virologic-suppression-for-hiv-positive-antiretroviral-treatment-experienced-women-after-switching-to-a-single-tablet-regimen-of-emtricitabine-rilpivirine-and-tenofovir-disoproxil-fumarate
#8
Prema Menezes, Katie Mollan, Erin Hoffman, Zimeng Xie, Jennifer Wills, Cheryl Marcus, John Rublein, Michael Hudgens, Joseph J Eron
BACKGROUND: Benefits of switching to a single-tablet regimen (STR) of FTC/RPV/TDF in virologically suppressed antiretroviral treatment experienced HIV-positive women include pregnancy category B rating and lack of clinically significant drug interactions between RPV and oral contraceptives. Unfortunately, studies involving switching to FTC/RPV/TDF enrolled fewer than 25% women. We undertook this 48 week study to assess the ability of virologically suppressed HIV-positive women switching to RPV STR to remain virologically suppressed and comply with the caloric intake requirement...
April 1, 2018: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29584723/transmission-of-hiv-1-drug-resistance-mutations-within-partner-pairs-a-cross-sectional-study-of-a-primary-hiv-infection-cohort
#9
Joanne D Stekler, Ross Milne, Rachel Payant, Ingrid Beck, Joshua Herbeck, Brandon Maust, Wenjie Deng, Kenneth Tapia, Sarah Holte, Janine Maenza, Claire E Stevens, James I Mullins, Ann C Collier, Lisa M Frenkel
BACKGROUND: Transmission of human immunodeficiency virus type 1 (HIV-1) drug resistance mutations, particularly that of minority drug-resistant variants, remains poorly understood. Population-based studies suggest that drug-resistant HIV-1 is less transmissible than drug-susceptible viruses. We compared HIV-1 drug-resistant genotypes among partner-pairs in order to assess the likelihood of transmission of drug resistance mutations and investigate the role of minority variants in HIV transmission...
March 2018: PLoS Medicine
https://www.readbyqxmd.com/read/29528852/fixed-dose-darunavir-boosted-with-cobicistat-combined-with-emtricitabine-and-tenofovir-alafenamide-fumarate
#10
Muge Cevik, Chloe Orkin
PURPOSE OF REVIEW: In an era when virological efficacy approaches 100%, novel antiretroviral (ARV) therapies must deliver better tolerability, safety, and convenient coformulated regimens. We review the phase II and III clinical data on the fixed dose combination (FDC) darunavir (DRV) 800mg / cobicistat (COBI/C) 150 mg / emtricitabine (F/FTC) 200 mg / tenofovir alafenamide fumarate (TAF) 10mg (D/C/F/TAF) for the treatment of HIV-1 infection. RECENT FINDINGS: In an exploratory phase II study, D/C/F/TAF FDC demonstrated similar virological efficacy to darunavir/cobicistat FDC + F /tenofovir disoproxil fumarate (TDF) FDC in treatment-naive HIV-1-infected individuals with favorable bone and renal outcomes...
March 9, 2018: Current Opinion in HIV and AIDS
https://www.readbyqxmd.com/read/29504269/brazilian-network-for-hiv-drug-resistance-surveillance-hiv-bresnet-a-survey-of-treatment-naive-individuals
#11
Monica B Arruda, Lídia T Boullosa, Cynthia C Cardoso, Carolina M da Costa, Carlos Rb Alves, Shirlene Ts de Lima, Helena T Kaminski, Agdemir W Aleixo, Ana Op Esposito, Ana Ms Cavalcanti, Maristela Riedel, José C Couto-Fernandez, Selma B Ferreira, Ivi Cm de Oliveira, Loreci E Portal, Hilda Hc Wolf, Sandra B Fernandes, Maria I de M C Pardini, Manoel Vc Feiteiro, Fernanda M Tolentino, Ricardo S Diaz, Giselle Isl Lopes, Roberta Bl Francisco, Nazle Mc Véras, Ana F Pires, Miriam Franchini, Fábio Mesquita, Amilcar Tanuri
INTRODUCTION: In Brazil, more than 487,450 individuals are currently undergoing antiretroviral treatment. In order to monitor the transmission of drug-resistant strains and HIV subtype distribution in the country, this work aimed to estimate its prevalence and to characterize the nationwide pretreatment drug resistance in individuals recently diagnosed with HIV between 2013 and 2015. METHODS: The HIV threshold survey methodology (HIV-THS, WHO) targeting antiretroviral-naive individuals with recent HIV diagnosis was utilized, and subjects were selected from 51 highly populated cities in all five Brazilian macroregions...
March 2018: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/29496619/the-association-between-arv-and-tb-drug-resistance-on-tb-treatment-outcome-among-kazakh-tb-hiv-patients
#12
Kathryn Mishkin, Kamiar Alaei, Elmira Alikeyeva, Christopher Paynter, Altyn Aringazina, Arash Alaei
INTRODUCTION: TB drug resistance poses a serious threat to the public health of Kazakhstan. This paper presents findings related to TB treatment outcome and drug resistant status among people coinfected with HIV and TB in Kazakhstan. METHODS: Cohort study using data were provided by the Kazakhstan Ministry of Health's National Tuberculosis Program for 2014 and 2015. Chi-square and logistical regression were performed to understand factors associated with drug resistant TB status and TB treatment outcome...
February 26, 2018: Journal of Global Antimicrobial Resistance
https://www.readbyqxmd.com/read/29473526/there-is-no-difference-between-sequences-of-hiv-1-infected-patients-with-stable-clinical-status-and-hiv-1-reference-sequence
#13
Marzyeh Nili, Katayoun Tayeri, Mohamad Gholami, Samaneh Moallemi, Farzaneh Sabahi, Saber Kalhori, Kazem Baesi, Mehrdad Hasibi
BACKGROUND: The rate of human immunodeficiency virus type 1 (HIV-1) infection in Iran has increased dramatically in the past few years. HIV-1 genome sequences are pivotal for large-scale studies of inter- and intra-host evolution. To understand the molecular difference between reference HIV-1 isolate and two HIV-1 infected patients in Iran, we conducted this study to analyze some genome segments of Iranian HIV-1 isolates. METHODS: Two HIV-1-infected individuals who were under antiretroviral therapy (ARV) for 8 years with stable clinical status were enrolled...
February 21, 2018: Infectious Disorders Drug Targets
https://www.readbyqxmd.com/read/29473485/high-virologic-failure-rates-with-maraviroc-based-salvage-regimens-among-indian-patients-a-preliminary-analysis-maraviroc-effectiveness-in-hiv-1-subtype-c
#14
Sanjay Pujari, Sunil Gaikwad, Vivek Bele, Kedar Joshi, Digamber Dabhade
BACKGROUND: There is no information on the clinical effectiveness of Maraviroc (MVC) amongst People Living with HIV (PLHIV) in India infected with HIV-1 Subtype C viruses. METHODS: We conducted a retrospective chart review of adult PLHIV on MVC based Antiretroviral (ARV) regimens for at least 6 months. Maraviroc was initiated amongst PLHIV with documented R5 tropic viruses (determined by in-house population sequencing of the V3 loop in triplicate and interpreted using the Geno2Pheno algorithm) in combination with an Optimized Background regimen (designed using genotypic resistance testing and past ARV history)...
January 2018: Journal of the International Association of Providers of AIDS Care
https://www.readbyqxmd.com/read/29401505/inflammatory-markers-the-tryptophan-kynurenine-pathway-and-vitamin-b-status-after-bariatric-surgery
#15
Monika H E Christensen, Dag J Fadnes, Therese H Røst, Eva R Pedersen, John R Andersen, Villy Våge, Arve Ulvik, Øivind Midttun, Per M Ueland, Ottar K Nygård, Gunnar Mellgren
OBJECTIVE: Obesity is associated with increased inflammation and insulin resistance. In conditions with chronic immune activation, low plasma vitamin B6-levels are described, as well as an increased kynurenine:tryptophan-ratio (KTR). We investigated circulating tryptophan, kynurenine and its metabolites, neopterin, B-vitamins, CRP, and HbA1c in individuals with obesity before and after bariatric surgery. METHODS: This longitudinal study included 37 patients with severe obesity, scheduled for bariatric surgery...
2018: PloS One
https://www.readbyqxmd.com/read/29338735/mental-health-service-utilization-is-associated-with-retention-in-care-among-persons-living-with-hiv-at-a-university-affiliated-hiv-clinic
#16
Lauren A Saag, Ashutosh R Tamhane, D Scott Batey, Michael J Mugavero, Ellen F Eaton
BACKGROUND: Mental health (MH) comorbidities reduce retention in care for persons living with HIV (PLWH) and are associated with poor health outcomes. Optimizing retention in primary care is vital, as poor retention is associated with delayed receipt of antiretroviral (ARV) therapy, ARV non-adherence, and poor health outcomes, including failure to suppress viral load, decreased CD4 counts, and clinically significant ARV drug resistance. We hypothesized that MH service utilization would be associated with improved retention in care for patients with HIV and MH comorbidities...
January 16, 2018: AIDS Research and Therapy
https://www.readbyqxmd.com/read/29230203/ibalizumab-targeting-cd4-receptors-an-emerging-molecule-in-hiv-therapy
#17
REVIEW
Simona A Iacob, Diana G Iacob
The HIV infection is responsible for the most devastating global pandemic of the last century. More than 39 million people have died of HIV/AIDS since 1981. The development of the antiretroviral (ARV) treatment begins with the discovery of zidovudine a nucleoside reverse transcriptase inhibitor. This breakthrough was followed by other ARV drug classes and representatives. Presently, HIV treatment employs 27 ARV representatives belonging to five different classes. Despite the proven benefits of ARV treatment and its long-term control of the HIV infection, there is an increasing concern about the numerous adverse effects and resistance to current ARV drugs...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29121950/the-hiv-1-integrase-ledgf-allosteric-inhibitor-mut-a-resistance-profile-impairment-of-virus-maturation-and-infectivity-but-without-influence-on-rna-packaging-or-virus-immunoreactivity
#18
Céline Amadori, Yme Ubeles van der Velden, Damien Bonnard, Igor Orlov, Nikki van Bel, Erwann Le Rouzic, Laia Miralles, Julie Brias, Francis Chevreuil, Daniele Spehner, Sophie Chasset, Benoit Ledoussal, Luzia Mayr, François Moreau, Felipe García, José Gatell, Alessia Zamborlini, Stéphane Emiliani, Marc Ruff, Bruno P Klaholz, Christiane Moog, Ben Berkhout, Montserrat Plana, Richard Benarous
BACKGROUND: HIV-1 Integrase (IN) interacts with the cellular co-factor LEDGF/p75 and tethers the HIV preintegration complex to the host genome enabling integration. Recently a new class of IN inhibitors was described, the IN-LEDGF allosteric inhibitors (INLAIs). Designed to interfere with the IN-LEDGF interaction during integration, the major impact of these inhibitors was surprisingly found on virus maturation, causing a reverse transcription defect in target cells. RESULTS: Here we describe the MUT-A compound as a genuine INLAI with an original chemical structure based on a new type of scaffold, a thiophene ring...
November 9, 2017: Retrovirology
https://www.readbyqxmd.com/read/29066507/pqr309-is-a-novel-dual-pi3k-mtor-inhibitor-with-preclinical-antitumor-activity-in-lymphomas-as-a-single-agent-and-in-combination-therapy
#19
Chiara Tarantelli, Eugenio Gaudio, Alberto J Arribas, Ivo Kwee, Petra Hillmann, Andrea Rinaldi, Luciano Cascione, Filippo Spriano, Elena Bernasconi, Francesca Guidetti, Laura Carrassa, Roberta Bordone Pittau, Florent Beaufils, Reto Ritschard, Denise Rageot, Alexander Sele, Barbara Dossena, Francesca Maria Rossi, Antonella Zucchetto, Monica Taborelli, Valter Gattei, Davide Rossi, Anastasios Stathis, Georg Stussi, Massimo Broggini, Matthias P Wymann, Andreas Wicki, Emanuele Zucca, Vladimir Cmiljanovic, Doriano Fabbro, Francesco Bertoni
Purpose: Activation of the PI3K/mTOR signaling pathway is recurrent in different lymphoma types, and pharmacologic inhibition of the PI3K/mTOR pathway has shown activity in lymphoma patients. Here, we extensively characterized the in vitro and in vivo activity and the mechanism of action of PQR309 (bimiralisib), a novel oral selective dual PI3K/mTOR inhibitor under clinical evaluation, in preclinical lymphoma models. Experimental Design: This study included preclinical in vitro activity screening on a large panel of cell lines, both as single agent and in combination, validation experiments on in vivo models and primary cells, proteomics and gene-expression profiling, and comparison with other signaling inhibitors...
January 1, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29045339/blood-pressure-response-to-renal-denervation-is-correlated-with-baseline-blood-pressure-variability-a-patient-level-meta-analysis
#20
Alexandre Persu, Daniel Gordin, Lotte Jacobs, Lutgarde Thijs, Michiel L Bots, Wilko Spiering, Atena Miroslawska, Jonas Spaak, Ján Rosa, Mark R de Jong, Elena Berra, Fadl Elmula M Fadl Elmula, Grégoire Wuerzner, Alison H M Taylor, Agnieszka Olszanecka, Danuta Czarnecka, Patrick B Mark, Michel Burnier, Jean Renkin, Sverre E Kjeldsen, Jiří Widimský, Arif Elvan, Thomas Kahan, Terje K Steigen, Peter J Blankestijn, Ilkka Tikkanen, Jan A Staessen
BACKGROUND: Sympathetic tone is one of the main determinants of blood pressure (BP) variability and treatment-resistant hypertension. The aim of our study was to assess changes in BP variability after renal denervation (RDN). In addition, on an exploratory basis, we investigated whether baseline BP variability predicted the BP changes after RDN. METHODS: We analyzed 24-h BP recordings obtained at baseline and 6 months after RDN in 167 treatment-resistant hypertension patients (40% women; age, 56...
October 16, 2017: Journal of Hypertension
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