Podcasts about integrase

This month, we're clearing the air around integrase inhibitors. They are by far the world's most commonly prescribed HIV drug class -- but that ubiquity has come with long-standing concerns around their potential to cause a range of adverse events, from weight gain to birth defects and more. Our executive editor Myles Helfand speaks with Laura Waters, M.D., FRCP, the head of the British HIV Association, about what the available science tells us.     Read the transcript: https://www.thebodypro.com/article/future-hiv-care-podcast-integrase-inhibitors-laura-waters      Credits: Our executive producer is Myles Helfand; our project manager is Alina Mogollon-Volk; our audio producers/engineers are Alex Portaluppi and Lucy Mueller; and our series editors are Maria Elena Perez and Juan Michael Porter II. This episode's audio was edited by Kim Buikema.

In this class, the virus is inside the cell however we stop its replication by inhibiting yet another enzyme. Just this year this class got a new drug, how encouraging is that! We are still adding on to the ARVs who knows cure could be around the corner.

While HIV treatment has come a long way over the decades, it still faces challenges. Specifically, HIV therapy such as integrase inhibitors have been associated with increased weight gain but the mechanism and extent of which has remained largely unknown. Listen in as Dave Hachey, HIV expert, and Geoff Wall discuss this and how it impacts medication selection when caring for patients with HIV.The Gamechanger: The risk of weight gain with integrase inhibitor and other potential HIV regimens should be discussed with patientsPatients' comorbidities should risk factors should be considered when determining an appropriate treatment regimenStudies suggest that the mechanism of weight gain from integrase inhibitors and older agents such as tenofovir alafenamide is different, although more research is neededShow Segments: 00:00 – Introductions04:36 – HIV Treatment & Weight Gain 07:27 – Integrase Inhibitors vs Tenofovir Alafenamide 17:12 – The GameChanger26:22 – Closing Remarks Guest Bios:David Hachey, PharmD, AAHIVP Professor Idaho State UniversityAfter graduating from the University of Rhode Island, Dr. Hachey completed a residency and fellowship in Family Medicine at Idaho State University. After, he stayed in Idaho and expanded his role with the College of Pharmacy and the Department of Family Medicine. Dr. Hachey has experience within the community setting and has also served as the director of the regional Ryan White HIV Clinic for the last 15-20 years. His vast experience gives him a unique perspective on the challenges pharmacists and patients face in preventing and managing HIV.   Links to Resources: Excess Weight Gain with Integrase Inhibitors and Tenofovir Alafenamide StudyHow to Claim CE:CE is available for CEimpact members. Click here to claim CPE CreditClick here to claim  CME CreditGet a membership:Join for CPE Credit Join for CME Credit References and resources: Wood B, Huhn G. Excess Weight Gain With Integrase Inhibitors and Tenofovir Alafenamide: What Is the Mechanism and Does It Matter?. Open Forum Infectious Diseases, Volume 8, Issue 12, December 2021. https://doi.org/10.1093/ofid/ofab542Continuing Education Information:Learning Objectives: Describe the proposed mechanism for weight gain due to integrase inhibitorsIdentify co-morbid conditions with HIV that may influence medication selectionDr. Wall is a member of the Janssen Speaker's Bureau. Dr. Hachey reports no actual or potential conflicts of interest associated with this episode.0.05 CEU | 0.5 HrsACPE UAN: 0107-0000-22-070-H01-PInitial release date: 01/03/22Expiration date: 01/03/2023Additional CPE & CME details can be found here

Dr. Burkhead, infectious diseases fellow at the University of South Florida, covers HIV History, the development of HIV antiviral therapy, and current treatment strategies in this comprehensive update. Dr. Burkhead begins by reviewing the different classes of antiretrovirals. He then traces the chronological history of antiretroviral development, from the initial trials of AZT through the introduction of other NRTIs, Protease inhibitors, NNRTIs, and the Integrase inhibitors. Next, Dr. Burkhead discusses antiretroviral therapy in special situations, such as in those who are pregnant, have chronic kidney disease, or cardiac disease. Important antiretroviral mutations are also discussed. Lastly, Dr. Burkhead closes the talk by discussing future directions for antiretroviral therapy.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.18.344481v1?rss=1 Authors: Wang, J. Y., Hoel, C. M., Al-Shayeb, B., Banfield, J. F., Brohawn, S. G., Doudna, J. A. Abstract: CRISPR-Cas systems provide adaptive immunity in bacteria and archaea by targeting foreign DNA for destruction using CRISPR RNA-guided enzymes. CRISPR immunity begins with integration of foreign sequences into the host CRISPR genomic locus, followed by transcription and maturation of CRISPR RNAs. In a few CRISPR systems, the Cas1 integrase and a Cas6 nuclease are fused to a reverse transcriptase that enables viral sequence acquisition from both DNA and RNA sources. To determine how these components work together, we determined a 3.7 [A] resolution cryo-EM structure of a Cas6-RT-Cas1 protein complexed with Cas2, a subunit of the CRISPR integrase. The structure and accompanying mutagenesis experiments provide evidence of bidirectional crosstalk between the Cas1 and RT active sites and unidirectional crosstalk from Cas6 to the Cas1 and RT active sites. Together, these findings suggest regulated structural rearrangements that may coordinate the complex's different enzymatic activities. Copy rights belong to original authors. Visit the link for more info

Hosts: Vincent Racaniello and Daniel Griffin Vincent and Daniel solve the case of the Family with Eosinophilia, and discuss HIV-1 infection and genome integration in the blood fluke Schistosoma mansoni. Become a patron of TWiP. Links for this episode: Family cluster of eosinophilia (Clin Inf Dis) Dientamoeba fragilis (Wikipedia) Parasites without borders HIV integrates into Schistosoma genome (PLoS Path) Image credit Letters read on TWiP 119 This episode is sponsored by CuriosityStream, a subscription streaming service that offers over 1,400 documentaries and non­fiction series from the world's best filmmakers. Get unlimited access starting at just $2.99 a month, and for our audience, the first two months are completely free if you sign up at curiositystream.com/microbe and use the promo code MICROBE. This episode is also sponsored by Drobo, a family of safe, expandable, yet simple to use storage arrays. Drobos are designed to protect your important data forever. Visit www.drobo.com to learn more. Case Study for TWiP 119 This one will be kinder and gentler case. Back in Thailand but could be in several places. 25 yo Thai woman from Bangkok, to hospital, chief complaint facial swelling. Eats typical Thai diet (see previous episodes!) Som tum, etc fish that is not cooked. Migratory - moves around face. Not tender, but mild itchiness. For about a week, no pain. Healthy, no past med/surg history, family all fine. HIV negative, no drugs, no travel. On examination, has swelling on right side, 3-4 cm raised, little redness, firm, does not feel like fluid filled. No fever, no GI problems, no bloods. WBC up, eosinophils up.  Send your case diagnosis, questions and comments to twip@microbe.tv

Host: Vincent Racaniello Guests: Kartik Chandran, Ganjam Kalpana, and Margaret Kielian Vincent travels to Albert Einstein College of Medicine where he speaks with Kartik, Ganjam, and Margaret about their work on Ebolavirus entry, a tumor suppressor that binds the HIV-1 integrase, and the entry of togaviruses and flaviviruses into cells. Links for this episode Antibodies that protect against Sudan virus (ACS Chem Biol) Ebola virus entry requires NPC1 (EMBO J) A toggle switch for virus entry (Nat Comm) Imaging alphavirus exit (J Virol) Defects in HIV-1 unable to interact with INI1 (Retrovirol) Cell cycle arrest by INI1 (Mol Cell Biol) Video of this episode - view at YouTube Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Vincent Racaniello and Glenn Rall meet up with Ann Skalka at the Fox Chase Cancer Center in Philadelphia and talk about her long and productive career in virology, from biochemistry to bacteriophage lambda to retroviruses. Don't miss an episode of MicrobeWorld Video. Subscribe for free using iTunes or help support our work by purchasing the MicrobeWorld podcast application for iPhone and Android devices in the iTunes or Android app stores.

Hosts: Vincent Racaniello and Glenn Rall Guest: Ann Skalka Vincent and Glenn meet up with Ann and talk about her long and productive career in virology, from biochemistry to bacteriophage lambda to retroviruses.   Links for this episode Skalka laboratory Asilomar Conference on recombinant DNA Unexpected inheritance (PLoS Path) Viral sequences in vertebrate genomes (J Virol) Assembly of integrase multimers (J Biol Chem) Cell cycle and retrovirus integration (J Cell Bioch) Video of this episode - view at YouTube Send your virology questions and comments (email or mp3 file) to twiv@twiv.tv

Vincent Racaniello and Glenn Rall meet up with Ann Skalka at the Fox Chase Cancer Center in Philadelphia and talk about her long and productive career in virology, from biochemistry to bacteriophage lambda to retroviruses. Don't miss an episode of MicrobeWorld Video. Subscribe for free using iTunes or help support our work by purchasing the MicrobeWorld podcast application for iPhone and Android devices in the iTunes or Android app stores.

Vincent Racaniello and Glenn Rall meet up with Ann Skalka at the Fox Chase Cancer Center in Philadelphia and talk about her long and productive career in virology, from biochemistry to bacteriophage lambda to retroviruses. Don't miss an episode of MicrobeWorld Video. Subscribe for free using iTunes or help support our work by purchasing the MicrobeWorld podcast application for iPhone and Android devices in the iTunes or Android app stores.

Die Bakteriophagen Integrase PhiC31 stellt ein viel versprechendes Werkzeug zur Integration genetischen Materials im nicht viral-basierten Gentransfer dar. Die PhiC31 Integrase vermittelt die Rekombination von spezifische Erkennungssequenz attB enthaltenden Plasmiden mit natürlich vorkommenden attP Erkennungssequenzen innerhalb des Zielgenoms mit unterschiedlicher Integrationsfrequenz und -spezifität. Nebeneffekte der Integration in Form von insertioneller Mutagenese, wie z.B. große Deletionen und chromosomale Veränderungen im Genom der Zielzelle konnten beobachtet werden. Ziel dieser Dissertation war, die PhiC31 vermittelte Effizienz zu verbessern und die Spezifität zu adressieren. Als Ansatz wurde die Mutagenese der DNA-Bindungsdomäne der Integrase basierend auf Punktmutanten zur verbesserten Integrationseffizienz gewählt. Integrationsassays wurden in verschiedenen humanen Zelllinien durchgeführt. Etablierung von Doppelmutanten, sowie Dosisoptimierung des Integrase kodierenden Plasmids verbesserten die Integrationseffizienz mehr als dreifach, verglichen mit der Wildtypintegrase in den Zelllinien HeLa und HCT. Weitere Assays verglichen die Exzisionsaktivität der Integrasemutanten mit dem Wildtyp. Bei fünf Mutanten wurde eine etwa zweifach erhöhte Exzision gefunden. Die Beurteilung der Spezifität der Integrasemutanten erfolgte durch Substitution der Wildtyp-attP Sequenz mit drei Pseudo attP Erkennungssequenzen des Reporterplasmids, deren erhöhte Spezifität bereits dokumentiert war. Einzelne Mutanten zeigten eine zweifach erhöhte Exzisionsaktivität. Die Rekombinationsaktivität von Integrasemutanten wurde im Kontext chromosomaler DNA mittels einer stabil GFP-exprimierenden Reporterzelllinie, in der die eGFP Expression mittels Integrase-vermittelter „Raus-Rekombination“ eines polyA Stoppsignals angeschaltet wird, untersucht. Auf chromosomaler Ebene wurde keine verbesserte Ausschneidungsaktivität erreicht. Zur Evaluierung der in vivo Effizienz zweier ausgewählter PhiC31 Integrasemutanten, die in vitro erhöhte Integrationsaktivität aufwiesen, wurden zwei Plasmide am C57BL/6 Mausmodell getestet. Reportergen war ein für den humanen Koagulationsfaktor IX kodierendes Gen. In Abhängigkeit von der Integrationseffizienz der Mutanten und des Wildtyps, wurden im Zeitraum von einhundert Tagen ähnliche Expressionslevel gefunden. Die Mutanten zeigten keine Verbesserung der Langzeitexpression von humanem Faktor IX. Die hier durchgeführten Studien zur Mutationsanalyse der Phagenintegrase PhiC31 zeigten einen wirksamen Ansatz zur Verbesserung der PhiC31 Integrase-vermittelten Integrationseffizienz in vitro.

Audio Journal of Global Health Issues Integrase Inhibitor Raltegravir Doubles Antiviral Response Rate in Treatment Experienced HIV-Infected Patients Compared to Optimised Background Therapy Alone REFERENCE: Abstract 105aLB, 105bLB, 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles February 25-28, 2007 ROY STEIGBIGEL, State University of New York at Stony Brook JOHN W. MELLORS, University of Pittsburgh Raltegravir doubled the antiviral response rate and the increase in CD4 cells among treatment-experienced HIV-infected patients who were resistant to at least one drug in each of the nucleoside, non-nucleoside, and protease inhibitor classes. Two placebo controlled trials (BENCHMRK-1 and BENCHMRK-2) randomized a total of almost 700 subjects to either raltegravir 400 mg twice daily or to placebo, each on a background of optimized antiviral background therapy. Raltegravir is an integrase inhibitor and acts to block the enzyme that allows HIV’s nuclei acid to integrate into the DNA of host cells.