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https://www.readbyqxmd.com/read/28219611/integrase-inhibitors-go-head-to-head
#1
Tristan Barber
No abstract text is available yet for this article.
February 14, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28219610/bictegravir-versus-dolutegravir-each-with-emtricitabine-and-tenofovir-alafenamide-for-initial-treatment-of-hiv-1-infection-a-randomised-double-blind-phase-2-trial
#2
Paul E Sax, Edwin DeJesus, Gordon Crofoot, Douglas Ward, Paul Benson, Robin Dretler, Anthony Mills, Cynthia Brinson, Julie Peloquin, Xuelian Wei, Kirsten White, Andrew Cheng, Hal Martin, Erin Quirk
BACKGROUND: All recent treatment guidelines recommend integrase strand transfer inhibitors (INSTIs) as components of initial HIV therapy. Bictegravir, a novel, once-daily, unboosted INSTI, showed potent activity in a 10 day monotherapy study and has a high in-vitro resistance barrier. On the basis of these results, we did a phase 2 trial comparing bictegravir with dolutegravir. METHODS: In this randomised, double-blind, phase 2 trial, we recruited previously untreated adults (aged ≥18 years) with HIV-1 infections from 22 outpatient centres in the USA...
February 14, 2017: Lancet HIV
https://www.readbyqxmd.com/read/28212411/lack-of-impact-of-pre-existing-t97a-hiv-1-integrase-mutation-on-integrase-strand-transfer-inhibitor-resistance-and-treatment-outcome
#3
Michael E Abram, Renee R Ram, Nicolas A Margot, Tiffany L Barnes, Kirsten L White, Christian Callebaut, Michael D Miller
T97A is an HIV-1 integrase polymorphism associated with integrase strand transfer inhibitor (INSTI) resistance. Using pooled data from 16 clinical studies, we investigated the prevalence of T97A (pre-existing and emergent) and its impact on INSTI susceptibility and treatment response in INSTI-naive patients who enrolled on elvitegravir (EVG)- or raltegravir (RAL)-based regimens. Prior to INSTI-based therapy, primary INSTI resistance-associated mutations (RAMs) were absent and T97A pre-existed infrequently (1...
2017: PloS One
https://www.readbyqxmd.com/read/28202942/duration-of-shiv-production-by-infected-cells-is-not-exponentially-distributed-implications-for-estimates-of-infection-parameters-and-antiviral-efficacy
#4
Catherine A A Beauchemin, Tomoyuki Miura, Shingo Iwami
The duration of the eclipse phase, from cell infection to the production and release of the first virion progeny, immediately followed by the virus-production phase, from the first to the last virion progeny, are important steps in a viral infection, by setting the pace of infection progression and modulating the response to antiviral therapy. Using a mathematical model (MM) and data for the infection of HSC-F cells with SHIV in vitro, we reconfirm our earlier finding that the eclipse phase duration follows a fat-tailed distribution, lasting 19 h (18-20 h)...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28196003/antiviral-activity-safety-and-pharmacokinetics-of-bictegravir-as-10-day-monotherapy-in-hiv-1-infected-adults
#5
Joel E Gallant, Melanie Thompson, Edwin DeJesus, Gene W Voskuhl, Xuelian Wei, Heather Zhang, Kirsten White, Andrew Cheng, Erin Quirk, Hal Martin
OBJECTIVE: to evaluate antiviral activity, safety, and pharmacokinetics of short-term monotherapy with bictegravir (bic), a novel, potent hiv integrase strand-transfer inhibitor (insti) DESIGN:: Phase 1b, randomized, double-blinded, adaptive, sequential cohort, placebo-controlled study METHODS:: HIV-infected adults not taking antiretroviral therapy were randomized to receive BIC (5, 25, 50, or 100 mg) or placebo once daily for 10 days. Primary endpoint was time-weighted average change from baseline to Day 11 (DAVG11) for plasma HIV-1 RNA...
February 8, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28195163/targeted-gene-knock-in-by-crispr-cas-ribonucleoproteins-in-porcine-zygotes
#6
Ki-Eun Park, Anne Powell, Shelley E S Sandmaier, Chan-Mi Kim, Alan Mileham, David M Donovan, Bhanu P Telugu
The domestic pig is an important "dual purpose" animal model for agricultural and biomedical applications. There is an emerging consensus in the biomedical community for the use of large animal models such as pigs to either serve as an alternative, or complement investigations from the mouse. However, the use of pig has not proven popular due to technical difficulties and time required in generating models with desired genetic modifications. In this regard, the ability to directly modify the genome in the zygote and generate edited animals is highly desirable...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28190823/probable-secondary-transmission-of-antimicrobial-resistant-escherichia-coli-between-people-living-with-and-without-pets
#7
Yeon Soo Chung, Young Kyung Park, Yong Ho Park, Kun Taek Park
Companion animals are considered as one of the reservoirs of antimicrobial-resistant (AR) bacteria that can be cross-transmitted to humans. However, limited information is available on the possibility of AR bacteria originating from companion animals being transmitted secondarily from owners to non-owners sharing the same space. To address this issue, the present study investigated clonal relatedness among AR E. coli isolated from dog owners and non-owners in the same college classroom or household. Anal samples (n=48) were obtained from 14 owners and 34 non-owners; 31 E...
February 11, 2017: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/28186334/a-novel-bxb1-integrase-rmce-system-for-high-fidelity-site-specific-integration-of-mab-expression-cassette-in-cho-cells
#8
Mara C Inniss, Kalpanie Bandara, Barbara Jusiak, Tim K Lu, Ron Weiss, Liliana Wroblewska, Lin Zhang
As CHO cell line development for biotherapeutic production becomes more sophisticated through the availability of the CHO genome sequence, the ability to accurately and reproducibly engineer the host cell genome has become increasingly important. Multiple well characterized systems for site-specific integration will enable more complex cell line engineering to generate cell lines with desirable attributes. We built and characterized a novel recombinase mediated cassette exchange (RMCE) system using Bxb1 integrase and compared it to the commonly used Flp/FRT RMCE system...
February 10, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/28184005/a-c-terminal-tail-region-in-the-rous-sarcoma-virus-integrase-provides-high-plasticity-of-functional-integrase-oligomerization-during-intasome-assembly
#9
Krishan K Pandey, Sibes Bera, Ke Shi, Hideki Aihara, Duane P Grandgenett
The retrovirus integrase (IN) inserts the viral cDNA into the host DNA genome. Atomic structures of five different retrovirus INs complexed with their respective viral DNA or branched viral/target DNA substrates have indicated these intasomes are composed of IN subunits ranging from tetramers, to octamers or to hexadecamers. IN precursors are monomers, dimers or tetramers in solution. But, how intasome assembly is controlled remains unclear. Therefore, we sought to unravel the functional mechanisms in different intasomes...
February 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28182989/6-cyclohexylmethyl-3-hydroxypyrimidine-2-4-dione-as-an-inhibitor-scaffold-of-hiv-reverase-transcriptase-impacts-of-the-3-oh-on-inhibiting-rnase-h-and-polymerase
#10
Jing Tang, Karen A Kirby, Andrew D Huber, Mary C Casey, Juan Ji, Daniel J Wilson, Stefan G Sarafianos, Zhengqiang Wang
3-Hydroxypyrimidine-2,4-dione (HPD) represents a versatile chemical core in the design of inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT)-associated RNase H and integrase strand transfer (INST). We report herein the design, synthesis and biological evaluation of an HPD subtype (4) featuring a cyclohexylmethyl group at the C-6 position. Antiviral testing showed that most analogues of 4 inhibited HIV-1 in the low nanomolar to submicromolar range, without cytotoxicity at concentrations up to 100 μM...
January 30, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28181950/clinicopathologic-and-molecular-pathology-of-collecting-duct-carcinoma-and-related-renal-cell-carcinomas
#11
REVIEW
An Na Seo, Ghilsuk Yoon, Jae Y Ro
Collecting duct carcinoma (CDC) and related tumors [ie, renal medullary carcinoma (RMC)] are rare types of highly aggressive renal cell carcinomas (RCC) with poor prognosis. Because of the rarity and diagnostic uncertainty of them, their molecular pathology and significance have not yet been fully elucidated. CDC, RMC, fumarate hydratase-deficient RCC (including hereditary leiomyomatosis and RCC-associated RCC HLRCC-RCC), and recently reported anaplastic lymphoma kinase (ALK)-rearrangement RCC have significant morphologic overlaps, but they are separately distinct entities having different molecular pathway and clinical settings...
March 2017: Advances in Anatomic Pathology
https://www.readbyqxmd.com/read/28177285/target-dna-bending-by-the-mu-transpososome-promotes-careful-transposition-and-prevents-its-reversal
#12
James Richard Fuller, Phoebe A Rice
The transposition of bacteriophage Mu serves as a model system for understanding DDE transposases and integrases. All available structures of these enzymes at the end of the transposition reaction, including Mu, exhibit significant bends in the transposition target site DNA. Here we use Mu to investigate the ramifications of target DNA bending on the transposition reaction. Enhancing the flexibility of the target DNA or prebending it increases its affinity for transpososomes by over an order of magnitude and increases the overall reaction rate...
February 8, 2017: ELife
https://www.readbyqxmd.com/read/28166800/a-purine-rich-element-in-foamy-virus-pol-regulates-env-splicing-and-gag-pol-expression
#13
Rebecca Moschall, Sarah Denk, Steffen Erkelenz, Christian Schenk, Heiner Schaal, Jochen Bodem
BACKGROUND: The foamy viral genome encodes four central purine-rich elements localized in the integrase-coding region of pol. Previously, we have shown that the first two of these RNA elements (A and B) are required for protease dimerization and activation. The D element functions as internal polypurine tract during reverse transcription. Peters et al., described the third element (C) as essential for gag expression suggesting that it might serve as an RNA export element for the unspliced genomic transcript...
February 6, 2017: Retrovirology
https://www.readbyqxmd.com/read/28158344/comment-on-integrase-strand-transfer-inhibitor-polymorphic-and-accessory-resistance-substitutions-in-patients-with-acute-recent-hiv-infection
#14
Claudia Fabrizio, Luciana Lepore, Antonella Lagioia, Grazia Punzi, Annalisa Saracino, Gioacchino Angarano, Laura Monno
No abstract text is available yet for this article.
January 31, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28139886/genomic-integration-of-the-full-length-dystrophin-coding-sequence-in-duchenne-muscular-dystrophy-induced-pluripotent-stem-cells
#15
Alfonso P Farruggio, Mital S Bhakta, Haley du Bois, Julia Ma, Michele P Calos
We developed plasmid vectors that express the full-length human dystrophin coding sequence in human cells. Dystrophin, the protein mutated in Duchenne muscular dystrophy, is extraordinarily large, providing challenges for cloning and plasmid production in E. coli. We expressed dystrophin from the strong, widely expressed CAG promoter, along with co-transcribed luciferase and mCherry marker genes useful for tracking plasmid expression. Introns were added at the 3' and 5' ends of the dystrophin sequence to prevent translation in E...
January 31, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/28134625/autophagy-facilitates-macrophage-depots-of-sustained-release-nanoformulated-antiretroviral-drugs
#16
Divya Prakash Gnanadhas, Prasanta K Dash, Brady Sillman, Aditya N Bade, Zhiyi Lin, Diana L Palandri, Nagsen Gautam, Yazen Alnouti, Harris A Gelbard, JoEllyn McMillan, R Lee Mosley, Benson Edagwa, Howard E Gendelman, Santhi Gorantla
Long-acting anti-HIV products can substantively change the standard of care for patients with HIV/AIDS. To this end, hydrophobic antiretroviral drugs (ARVs) were recently developed for parenteral administration at monthly or longer intervals. While shorter-acting hydrophilic drugs can be made into nanocarrier-encased prodrugs, the nanocarrier encasement must be boosted to establish long-acting ARV depots. The mixed-lineage kinase 3 (MLK-3) inhibitor URMC-099 provides this function by affecting autophagy. Here, we have shown that URMC-099 facilitates ARV sequestration and its antiretroviral responses by promoting the nuclear translocation of the transcription factor EB (TFEB)...
January 30, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28134057/hiv-viral-kinetics-and-t-cell-dynamics-in-antiretroviral-na%C3%A3-ve-persons-starting-an-integrase-strand-transfer-inhibitor-and-protease-inhibitor-regimen
#17
Maile Y Karris, Sonia Jain, Tyler R C Day, Josué Pérez-Santiago, Miguel Goicoechea, Michael P Dubé, Xiaoying Sun, Celsa Spina, Eric S Daar, Richard H Haubrich, Sheldon Morris
BACKGROUND: Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens may potentially minimize antiretroviral (ART) toxicities, but demonstrate mixed efficacy and toxicity results. The impact of an integrase strand transfer inhibitor (INSTI) and protease inhibitor (PI) regimen on HIV viral dynamics and T cell kinetics remains underdescribed. OBJECTIVE: To compare the effect of raltegravir + ritonavir boosted lopinavir (RAL + LPV/r) to efavirenz/tenofovir disoproxil fumarate/emtricitabine (EFV/TDF/FTC) on HIV kinetics and T cell dynamics...
January 30, 2017: HIV Clinical Trials
https://www.readbyqxmd.com/read/28124959/-prevalence-of-human-leukocyte-antigen-hla-b-57-01-in-hiv-infected-patients
#18
Aydın Deveci, Ahmet Yılmaz Çoban, Belma Durupınar
Deaths related with human immunodeficiency virus (HIV) infections have been decreased by the introduction of combined anti-retroviral therapy (ART) into the clinical practice. Combined ART usually consists of two nucleoside/nucleotide analogs reverse transcriptase inhibitors (NRTI) that is called backbone and a third drug that belongs to either non-nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI), integrase strand transfer inhibitors (INSTI) or entry inhibitors. During abacavir therapy which is a member of NRTI, hypersensitivity reactions can occur approximately 4-9% of the patients that lead difficulties for the management of HIV infections...
October 2016: Mikrobiyoloji Bülteni
https://www.readbyqxmd.com/read/28122976/the-fact-complex-promotes-avian-leukosis-virus-dna-integration
#19
Shelby Winans, Ross C Larue, Carly M Abraham, Nikolozi Shkriabai, Amelie Skopp, Duane Winkler, Mamuka Kvaratskhelia, Karen L Beemon
: All retroviruses need to integrate a DNA copy of their genome into the host chromatin. Cellular proteins regulating and targeting lentiviral and gammaretroviral integration in infected cells have been discovered, but the factors that mediate alpharetroviral avian leukosis virus (ALV) integration are unknown. Here, we have identified the FACT protein complex, which consists of SSRP1 and Spt16, as a principal cellular binding partner of ALV integrase (IN). Biochemical experiments with purified recombinant proteins show that SSRP1 and Spt16 are able to individually bind ALV IN, but only the FACT complex effectively stimulates ALV integration activity in vitro Likewise, in infected cells, the FACT complex promotes ALV integration activity with proviral integration frequency varying directly with cellular expression levels of the FACT complex...
January 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28118801/early-clinical-experience-of-dolutegravir-in-an-hiv-cohort-in-a-larger-teaching-hospital
#20
Sej Todd, P Rafferty, E Walker, M Hunter, W W Dinsmore, C M Donnelly, E J McCarty, S P Quah, C R Emerson
Dolutegravir (DTG) is the third HIV integrase inhibitor (INI) available for prescription in Belfast since July 2014. It has shown high virological efficacy in both treatment-naïve and -experienced patients. We carried out a retrospective case chart analysis of HIV-1-positive adults commenced on DTG between July 2014 and September 2015. Patients were identified from records as either treatment-naïve or antiretroviral therapy (ART) experienced. Outcomes included: (1) virological response (HIV-1 RNA viral load at 0, 4, 8 and 12 weeks), (2) immunological response (CD4+ cell count at 0, 4, 8 and 12 weeks) and (3) tolerability (side effects and discontinuation)...
January 1, 2017: International Journal of STD & AIDS
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