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Arv resistance

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
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
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
Kazem Baesi, Marzyeh Nili, Katayoun Tayeri, Mohamad Gholami, Samaneh Moallemi, Farzaneh Sabahi, Saber Kalhori, 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
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
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
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
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
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
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
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
Rachel A Silverman, Ingrid A Beck, Catherine Kiptinness, Molly Levine, Ross Milne, Christine J McGrath, Steve Bii, Barbra A Richardson, Grace John-Stewart, Bhavna Chohan, Samah R Sakr, James N Kiarie, Lisa M Frenkel, Michael H Chung
Background: Pre-antiretroviral-treatment drug resistance (PDR) is a predictor of HIV treatment failure. We determined PDR-prevalence and correlates in a Kenyan cohort. Methods: We conducted a cross-sectional analysis of antiretroviral (ARV) treatment-eligible HIV-infected participants in 2013-2014 at three clinics. PDR was defined as ≥2% mutant-frequency in a participant's HIV-quasispecies at pol codons K103N, Y181C, G190A, M184 V, or K65R by oligonucleotide ligation assay...
October 10, 2017: Journal of Infectious Diseases
Clara Strauss, Kenneth Hugdahl, Flavie Waters, Mark Hayward, Josef J Bless, Liv E Falkenberg, Bodil Kråkvik, Arve Egil Asbjørnsen, Erik Johnsen, Igne Sinkeviciute, Rune A Kroken, Else-Marie Løberg, Neil Thomas
Hallucinated voices are common across psychiatric and non-clinical groups. The predominant cognitive theory about the impact of voices posits that beliefs about voice power ('Omnipotence') and voice intent ('Malevolence'/'Benevolence') play a key role in determining emotional and behavioral reactions. The revised Beliefs about Voices Questionnaire (BAVQ-R) was designed to assess these constructs, together with two styles of responding (Engagement and Resistance). The BAVQ-R is widely used in clinical and research settings, yet it has not received validation of its constructs and factor structure...
October 5, 2017: Psychiatry Research
Arash Memarnejadian, Hamed Gouklani, Samira Mohammadi, Masoomeh Moosazadeh, Joshua Choi
HIV-1 transmitted drug resistance (TDR) occurs when primary viruses bear drug resistance mutations (DRMs). TDR causes first-line antiretroviral (ARV) therapy (ART) failure and is becoming more pronounced due to the widespread use of ART. With the absence of routine individual-level drug resistance testing, the World Health Organization (WHO) recommends the tracking of TDR mutations and optimizing the first-line ART following pre-treatment drug resistance (PDR) surveys. Here, we report the PDR frequency for the first time in Hormozgan, a southern province of Iran...
October 5, 2017: Archives of Virology
Sana-Kay Whyte-Allman, Md Tozammel Hoque, Mohammad-Ali Jenabian, Jean-Pierre Routy, Reina Bendayan
Poor antiretroviral drug (ARV) penetration in the testes could be due, in part, to the presence of ATP-binding cassette (ABC) membrane-associated drug efflux transporters such as P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins (MRPs) expressed at the blood-testis barrier (BTB). The functional expression of these transporters is known to be regulated by ligand-activated nuclear receptors pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in various tissues...
December 2017: Journal of Pharmacology and Experimental Therapeutics
Robert W Shafer
As treatment options coalesce around a smaller number of antiretroviral drugs (ARVs), data are emerging on the drug resistance mutations (DRMs) selected by the most widely used ARVs and on the impact of these DRMs on ARV susceptibility and virological response to first- and later-line treatment regimens. Recent studies have described the DRMs that emerge in patients receiving tenofovir prodrugs, the nonnucleoside reverse transcriptase inhibitors efavirenz and rilpivirine, ritonavir-boosted lopinavir, and the integrase inhibitors raltegravir and elvitegravir...
December 1, 2017: Journal of Infectious Diseases
Letícia M Raposo, Flavio F Nobre
Resistance to antiretrovirals (ARVs) is a major problem faced by HIV-infected individuals. Different rule-based algorithms were developed to infer HIV-1 susceptibility to antiretrovirals from genotypic data. However, there is discordance between them, resulting in difficulties for clinical decisions about which treatment to use. Here, we developed ensemble classifiers integrating three interpretation algorithms: Agence Nationale de Recherche sur le SIDA (ANRS), Rega, and the genotypic resistance interpretation system from Stanford HIV Drug Resistance Database (HIVdb)...
August 30, 2017: Journal of Medical Systems
Olivier Sheik Amamuddy, Nigel T Bishop, Özlem Tastan Bishop
BACKGROUND: Drug resistance in HIV treatment is still a worldwide problem. Predicting resistance to antiretrovirals (ARVs) before starting any treatment is important. Prediction accuracy is essential, as low-accuracy predictions increase the risk of prescribing sub-optimal drug regimens leading to patients developing resistance sooner. Artificial Neural Networks (ANNs) are a powerful tool that would be able to assist in drug resistance prediction. In this study, we constrained the dataset to subtype B, sacrificing generalizability for a higher predictive performance, and demonstrated that the predictive quality of the ANN regression models have definite improvement for most ARVs...
August 15, 2017: BMC Bioinformatics
M A Kuti, J O Akinyemi, B O Ogunbosi, K M Kuti, O A Adesina, O A Awolude, O S Michael, I F Adewole
OBJECTIVES: To determine the metabolic abnormalities among Hepatitis C Virus (HCV) co infected HAART naïve HIV infected persons within the adult ARV clinic of the University College Hospital/University of Ibadan, Ibadan, Nigeria Methods: This was a retrospective study involving the review of clinical records of newly recruited HIV-infected persons in the adult antiretroviral (ARV) clinic over a 12 month period (January - December 2006). Baseline results for fasting plasma glucose (FPG) and fasting lipid profile were retrieved...
July 2017: Nigerian Journal of Clinical Practice
Roger Paredes, Philip L Tzou, Gert van Zyl, Geoff Barrow, Ricardo Camacho, Sergio Carmona, Philip M Grant, Ravindra K Gupta, Raph L Hamers, P Richard Harrigan, Michael R Jordan, Rami Kantor, David A Katzenstein, Daniel R Kuritzkes, Frank Maldarelli, Dan Otelea, Carole L Wallis, Jonathan M Schapiro, Robert W Shafer
INTRODUCTION: HIV-1 genotypic resistance test (GRT) interpretation systems (IS) require updates as new studies on HIV-1 drug resistance are published and as treatment guidelines evolve. METHODS: An expert panel was created to provide recommendations for the update of the Stanford HIV Drug Resistance Database (HIVDB) GRT-IS. The panel was polled on the ARVs to be included in a GRT report, and the drug-resistance interpretations associated with 160 drug-resistance mutation (DRM) pattern-ARV combinations...
2017: PloS One
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