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https://www.readbyqxmd.com/read/28721059/cost-effectiveness-analysis-of-dolutegravir-plus-backbone-compared-with-raltegravir-plus-backbone-darunavir-ritonavir-plus-backbone-and-efavirenz-tenofovir-emtricitabine-in-treatment-na%C3%A3-ve-and-experienced-hiv-positive-patients
#1
Umberto Restelli, Giuliano Rizzardini, Andrea Antinori, Adriano Lazzarin, Marzia Bonfanti, Paolo Bonfanti, Davide Croce
BACKGROUND: In January 2014, the European Medicines Agency issued a marketing authorization for dolutegravir (DTG), a second-generation integrase strand transfer inhibitor for HIV treatment. The study aimed at determining the incremental cost-effectiveness ratio (ICER) of the use of DTG+backbone compared with raltegravir (RAL)+backbone, darunavir (DRV)+ritonavir(r)+backbone and efavirenz/tenofovir/emtricitabine (EFV/TDF/FTC) in HIV-positive treatment-naïve patients and compared with RAL+backbone in treatment-experienced patients, from the Italian National Health Service's point of view...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28717247/characterization-of-hiv-1-integrase-interaction-with-human-ku70-protein-and-initial-implications-for-drug-targeting
#2
Andrey N Anisenko, Ekaterina S Knyazhanskaya, Artur O Zalevsky, Julia Yu Agapkina, Aleksander I Sizov, Timofey S Zatsepin, Marina B Gottikh
Human Ku70/Ku80 protein is known to influence HIV-1 replication. One of the possible reasons may be the protection of integrase from proteasomal degradation by Ku70 subunit. We demonstrated that recombinant HIV-1 integrase and Ku70 form a stable complex, while no interaction of Ku70 with integrase from prototype foamy virus was observed. By analyzing protein subdomains we determined two binding sites in the structure of both Ku70 and integrase: the 51-160 a.a. region of integrase interacts with residues 251-438 of Ku70, whereas Ku70 N-terminal domain (1-250 a...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28715460/early-infant-diagnosis-of-hiv-1-infection-in-luanda-angola-using-a-new-dna-pcr-assay-and-dried-blood-spots
#3
Francisco Martin, Claudia Palladino, Rita Mateus, Anna Bolzan, Perpétua Gomes, José Brito, Ana Patrícia Carvalho, Yolanda Cardoso, Cristovão Domingos, Vanda Sofia Lôa Clemente, Nuno Taveira
BACKGROUND: Early diagnosis and treatment reduces HIV-1-related mortality, morbidity and size of viral reservoirs in infants infected perinatally. Commercial molecular tests enable the early diagnosis of infection in infants but the high cost and low sensitivity with dried blood spots (DBS) limit their use in sub-Saharan Africa. OBJECTIVES: To develop and validate a sensitive and cheap qualitative proviral DNA PCR-based assay for early infant diagnosis (EID) in HIV-1-exposed infants using DBS samples...
2017: PloS One
https://www.readbyqxmd.com/read/28715160/meeting-the-who-90-target-antiretroviral-treatment-efficacy-in-poland-is-associated-with-baseline-clinical-patient-characteristics
#4
Milosz Parczewski, Ewa Siwak, Magdalena Leszczyszyn-Pynka, Iwona Cielniak, Ewa Burkacka, Piotr Pulik, Adam Witor, Karolina Muller, Ewelina Zasik, Anna Grzeszczuk, Maria Jankowska, Małgorzata Lemańska, Anita Olczak, Edyta Grąbczewska, Aleksandra Szymczak, Jacek Gąsiorowski, Bartosz Szetela, Monika Bociąga-Jasik, Paweł Skwara, Magdalena Witak-Jędra, Elżbieta Jabłonowska, Kamila Wójcik-Cichy, Juliusz Kamerys, Małgorzata Janczarek, Dagny Krankowska, Tomasz Mikuła, Katarzyna Kozieł, Dariusz Bielec, Justyna Stempkowska, Aleksandra Kocbach, Wiesława Błudzin, Andrzej Horban
INTRODUCTION: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. M: ethods Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres...
July 17, 2017: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/28711829/prevalence-of-antibiotic-resistance-genes-in-soils-after-continually-applied-with-different-manure-for-30-years
#5
Shuang Peng, Youzhi Feng, Yiming Wang, Xisheng Guo, Haiyan Chu, Xiangui Lin
A 30year field experiment with a wheat-soybean cropping system were performed to compare the long-term anthropogenic influence on soil ARGs. Compared with chemical fertilization, the occurrence of 38 ARGs and the abundance of seven ARGs (tetL, tetB(P), tetO, tetW, sul1, ermB, and ermF) were significantly increased by long term exposure of pig manure. However, application of wheat straw and cow manure not substantially affected the abundance of ARGs except cow manure increased the abundance of tetM and tetW to a detectable level...
June 27, 2017: Journal of Hazardous Materials
https://www.readbyqxmd.com/read/28705967/genome-sequence-of-mycobacterium-phage-crystalp
#6
Christine L Fleischacker, Miriam Segura-Totten, Rebecca A Garlena, Deborah Jacobs-Sera, Welkin H Pope, Daniel A Russell, Graham F Hatfull
Mycobacteriophage CrystalP is a newly isolated phage infecting Mycobacterium smegmatis strain mc(2)155. CrystalP has a 76,483-bp genome and is predicted to contain 143 protein-coding and 2 tRNA genes, including repressor and integrase genes consistent with a temperate lifestyle. CrystalP is related to the mycobacteriophages Toto and Kostya and to other Cluster E phages.
July 13, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28700573/crispr-cas-encoding-of-a-digital-movie-into-the-genomes-of-a-population-of-living-bacteria
#7
Seth L Shipman, Jeff Nivala, Jeffrey D Macklis, George M Church
DNA is an excellent medium for archiving data. Recent efforts have illustrated the potential for information storage in DNA using synthesized oligonucleotides assembled in vitro. A relatively unexplored avenue of information storage in DNA is the ability to write information into the genome of a living cell by the addition of nucleotides over time. Using the Cas1-Cas2 integrase, the CRISPR-Cas microbial immune system stores the nucleotide content of invading viruses to confer adaptive immunity. When harnessed, this system has the potential to write arbitrary information into the genome...
July 12, 2017: Nature
https://www.readbyqxmd.com/read/28698278/on-the-origin-of-reverse-transcriptase-using-crispr-cas-systems-and-their-hyperdiverse-enigmatic-spacer-repertoires
#8
Sukrit Silas, Kira S Makarova, Sergey Shmakov, David Páez-Espino, Georg Mohr, Yi Liu, Michelle Davison, Simon Roux, Siddharth R Krishnamurthy, Becky Xu Hua Fu, Loren L Hansen, David Wang, Matthew B Sullivan, Andrew Millard, Martha R Clokie, Devaki Bhaya, Alan M Lambowitz, Nikos C Kyrpides, Eugene V Koonin, Andrew Z Fire
Cas1 integrase is the key enzyme of the clustered regularly interspaced short palindromic repeat (CRISPR)-Cas adaptation module that mediates acquisition of spacers derived from foreign DNA by CRISPR arrays. In diverse bacteria, the cas1 gene is fused (or adjacent) to a gene encoding a reverse transcriptase (RT) related to group II intron RTs. An RT-Cas1 fusion protein has been recently shown to enable acquisition of CRISPR spacers from RNA. Phylogenetic analysis of the CRISPR-associated RTs demonstrates monophyly of the RT-Cas1 fusion, and coevolution of the RT and Cas1 domains...
July 11, 2017: MBio
https://www.readbyqxmd.com/read/28696279/defining-the-functionally-important-domain-and-amino-acid-residues-in-mycobacterium-tuberculosis-integration-host-factor-for-genome-stability-dna-binding-and-integrative-recombination
#9
Narayanaswamy Sharadamma, Yadumurthy Harshavardhana, Kalappa Muniyappa
The integration host factor of Mycobacterium tuberculosis (mIHF) consists of a single polypeptide chain, the product of the ihf gene. We previously revealed that mIHF is a novel member of a new class of nucleoid-associated proteins that have important roles in DNA damage response, nucleoid compaction and integrative recombination. The mIHF contains a region of 86 amino acids at its N-terminus, absent in both α- and β-subunits of Escherichia coli IHF. However, the functional significance of an extra 86-amino acid region in the full-length protein remains unknown...
July 10, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28692546/hhv8-and-kaposi-s-sarcoma-should-we-really-give-up-protease-inhibitors-in-all-hiv-infected-patients
#10
Patrick Philibert, Laurent Chiche, Sylvie Caillères, Julie Allemand, Stanislas Rebaudet, Marion Delord, Chloé Stavris, Frédérique Retornaz, Hacène Khiri, Philippe Halfon
We describe the first case of a patient presenting Kaposi's Sarcoma with HHV8 viremia after switching from a protease inhibitor (PI) to an integrase inhibitor-based combination antiretroviral therapy, followed by a rapid remission when resuming PI. We suggest that the recent recommendations to switch all HIV patients to PI-free regimens should be carefully reevaluated especially in men who have sex with men HIV patients which are at higher risks of HHV8 infections and associated malignancies.
July 7, 2017: AIDS
https://www.readbyqxmd.com/read/28692532/cardiovascular-outcomes-among-hiv-infected-veterans-receiving-atazanavir-a-us-national-historical-cohort-study
#11
Joanne Lafleur, Adam P Bress, Lisa Rosenblatt, Jacob Crook, Paul E Sax, Joel Myers, Corey Ritchings
OBJECTIVE: Patients with HIV infection have an increased risk of cardiovascular disease compared with uninfected individuals. Antiretroviral therapy with atazanavir delays progression of atherosclerosis markers; whether this reduces cardiovascular disease event risk compared with other antiretroviral regimens is currently unknown. DESIGN: Population-based, non-interventional, historical cohort study conducted from July 1, 2003, through December 31, 2015. SETTING: Veterans Health Administration (VHA) hospitals and clinics throughout the United States...
July 7, 2017: AIDS
https://www.readbyqxmd.com/read/28689442/drug-interactions-in-hiv-infected-patients-treated-for-hepatitis-c
#12
Vicente Soriano, Pablo Labarga, José V Fernandez-Montero, Carmen de Mendoza, Laura Benítez-Gutiérrez, José M Peña, Pablo Barreiro
The introduction of direct-acting antivirals (DAA) has revolutionized the hepatitis C field. Most hepatitis C patients can now be cured, including those coinfected with HIV. However, drug-drug interactions (DDI) between DAA and antiretrovirals (ARV) should be known to prevent either toxicity due to drug overexposure or treatment failures due to low drug concentrations. Areas covered: Clinically significant DDI may be classified as major (when co-administration should be contraindicated) or minor (when they require close monitoring, changes in drug dosage or in timing)...
July 13, 2017: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/28683645/substitution-of-nevirapine-or-raltegravir-for-protease-inhibitor-vs-rosuvastatin-treatment-for-the-management-of-dyslipidaemia-in-hiv-infected-patients-on-stable-antiretroviral-therapy-nevrast-study
#13
Leonardo Calza, Eleonora Magistrelli, Vincenzo Colangeli, Marco Borderi, Linda Bussini, Isabella Bon, Maria Carla Re, Pierluigi Viale
OBJECTIVES: An observational, prospective, cohort study was performed to compare efficacy and safety of a switch from ritonavir-boosted protease inhibitor (PI/r) to nevirapine or raltegravir with that of rosuvastatin addition to current antiretroviral therapy in HIV-infected patients with hyperlipidaemia. METHODS: All HIV-infected patients receiving a stable PI/r-based antiretroviral regimen, with persistently suppressed viremia, naïve to non-nucleoside analogues and to integrase strand transfer inhibitors, with mixed hyperlipidaemia, and who underwent a switch from PI/r to nevirapine (Group A) or raltegravir (Group B) or who started rosuvastatin at 10 mg daily (group C) with unchanged antiretroviral regimen were enrolled into the study...
July 6, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28681118/naturally-occurring-vpr-inhibitors-from-medicinal-plants-of-myanmar
#14
REVIEW
Nwet Nwet Win, Hla Ngwe, Ikuro Abe, Hiroyuki Morita
Human immunodeficiency virus type-1 (HIV-1) is a lentiviral family member that encodes the retroviral Gag, Pol, and Env proteins, along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. The currently approved anti-HIV drugs target the Pol and Env encoded proteins. However, these drugs are only effective in reducing viral replication. Furthermore, the drugs' toxicities and the emergence of drug-resistant strains have become serious worldwide problems. Resistance eventually arises to all of the approved anti-HIV drugs, including the newly approved drugs that target HIV integrase (IN)...
July 5, 2017: Journal of Natural Medicines
https://www.readbyqxmd.com/read/28678879/treatment-with-integrase-inhibitor-suggests-a-new-interpretation-of-hiv-rna-decay-curves-that-reveals-a-subset-of-cells-with-slow-integration
#15
E Fabian Cardozo, Adriana Andrade, John W Mellors, Daniel R Kuritzkes, Alan S Perelson, Ruy M Ribeiro
The kinetics of HIV-1 decay under treatment depends on the class of antiretrovirals used. Mathematical models are useful to interpret the different profiles, providing quantitative information about the kinetics of virus replication and the cell populations contributing to viral decay. We modeled proviral integration in short- and long-lived infected cells to compare viral kinetics under treatment with and without the integrase inhibitor raltegravir (RAL). We fitted the model to data obtained from participants treated with RAL-containing regimes or with a four-drug regimen of protease and reverse transcriptase inhibitors...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28672885/characterization-of-sinorhizobium-sp-lm21-prophages-and-virus-encoded-dna-methyltransferases-in-the-light-of-comparative-genomic-analyses-of-the-sinorhizobial-virome
#16
Przemyslaw Decewicz, Monika Radlinska, Lukasz Dziewit
The genus Sinorhizobium/Ensifer mostly groups nitrogen-fixing bacteria that create root or stem nodules on leguminous plants and transform atmospheric nitrogen into ammonia, which improves the productivity of the plants. Although these biotechnologically-important bacteria are commonly found in various soil environments, little is known about their phages. In this study, the genome of Sinorhizobium sp. LM21 isolated from a heavy-metal-contaminated copper mine in Poland was investigated for the presence of prophages and DNA methyltransferase-encoding genes...
June 26, 2017: Viruses
https://www.readbyqxmd.com/read/28672785/comprehensive-expression-profiling-and-functional-network-analysis-of-porphyra-334-one-mycosporine-like-amino-acid-maa-in-human-keratinocyte-exposed-with-uv-radiation
#17
Sung-Suk Suh, Sung Gu Lee, Ui Joung Youn, Se Jong Han, Il-Chan Kim, Sanghee Kim
Mycosporine-like amino acids (MAAs) have been highlighted as pharmacologically active secondary compounds to protect cells from harmful UV-radiation by absorbing its energy. Previous studies have mostly focused on characterizing their physiological properties such as antioxidant activity and osmotic regulation. However, molecular mechanisms underlying their UV-protective capability have not yet been revealed. In the present study, we investigated the expression profiling of porphyra-334-modulated genes or microRNA (miRNAs) in response to UV-exposure and their functional networks, using cDNA and miRNAs microarray...
June 24, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28666339/control-of-serine-integrase-recombination-directionality-by-fusion-with-the-directionality-factor
#18
Femi J Olorunniji, Arlene L McPherson, Susan J Rosser, Margaret C M Smith, Sean D Colloms, W Marshall Stark
Bacteriophage serine integrases are extensively used in biotechnology and synthetic biology for assembly and rearrangement of DNA sequences. Serine integrases promote recombination between two different DNA sites, attP and attB, to form recombinant attL and attR sites. The 'reverse' reaction requires another phage-encoded protein called the recombination directionality factor (RDF) in addition to integrase; RDF activates attL × attR recombination and inhibits attP × attB recombination. We show here that serine integrases can be fused to their cognate RDFs to create single proteins that catalyse efficient attL × attR recombination in vivo and in vitro, whereas attP × attB recombination efficiency is reduced...
June 28, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28665147/s-mar-element-facilitates-episomal-long-term-persistence-of-adeno-associated-viral-aav-vector-genomes-in-proliferating-cells
#19
Claudia Hagedorn, Maria Schnödt, Philip Boehme, Heba Abdelrazik, Hans Lipps, Hildegard Büning
Adeno-associated viral (AAV) vectors are one of the most frequently applied gene transfer system in research and human clinical trials. Since AAV vectors do not possess an integrase activity, application is restricted to terminally differentiated tissues if transgene expression is required long-term. To overcome this limitation and to generate AAV vectors that persist episomally in dividing cells, we equipped AAV vector genomes with an autonomous replicating unit (Scaffold/matrix attachment region (S/MAR))...
June 30, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28664942/darunavir-stands-up-as-preferred-hiv-protease-inhibitor
#20
Josep Mallolas
Current antiretroviral therapy reaches and maintains viral suppression over the years in more than 90% of treated HIV-infected individuals. Although integrase inhibitors are the preferred third agent in antiretroviral therapy in the current guidelines, rilpivirine, a non-nucleoside reverse transcrip- tase inhibitor, and darunavir (DRV), a second-generation protease inhibitor, are the preferred third companion to be used along with a backbone of two nucleos(t)ide reverse transcriptase inhibitors as first-line triple HIV combination treatment...
April 2017: AIDS Reviews
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