DOCSLIB.ORG

Supplementary Appendix

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Supplementary Appendix Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Swindells S, Andrade-Villanueva J-F, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med 2020;382:1112-23. DOI: 10.1056/NEJMoa1904398 (PDF updated March 26, 2020) Susan Swindells, et al. Long-Acting Cabotegravir and Rilpivirine for HIV-1 (ATLAS Trial) SUPPLEMENTARY APPENDIX Contents Study Sites and Lead Investigators ............................................................................................................... 2 Eligibility Criteria ........................................................................................................................................... 6 Figure S1. Timeliness of Injections Relative to Target. ............................................................................... 14 Figure S2. Unadjusted Difference (LA Arm Minus CAR Arm) in Percentage Proportion with HIV-1 RNA ≥50 copies/mL at Week 48 (Snapshot) ± 95% CI. ............................................. 15 Figure S3. Incidence of Injection Site Reaction Adverse Events, LA Arm.................................................... 16 Table S1. Summary of Antiretroviral Agents Taken at Baseline. ................................................................ 17 Table S2. Reasons for Exclusion From the Per-Protocol Population .......................................................... 18 Table S3. Additional Secondary Endpoints ................................................................................................. 19 Table S4. Confirmed Virologic Failure. ........................................................................................................ 20 Table S5. On-treatment Adverse Events by System Organ Class and Maximum Toxicity Grade – Maintenance Phase ......................................................................................... 21 Table S6. Serious Adverse Events – Maintenance Phase. ........................................................................... 37 Table S7. Adverse Events Leading to Withdrawal – Maintenance Phase. .................................................. 38 Table S8. On-treatment Laboratory Abnormalities by Maximum Toxicity Grade – Maintenance Phase ....................................................................................................... 39 Table S9. Cabotegravir and Rilpivirine Plasma Concentrations in LA Recipients with Confirmed Virologic Failure. ............................................................................................... 40 Table S10. Change from Baseline in Total Treatment Satisfaction Score by Visit – Adjusted, Last Observation Carried Forward. ............................................................................................. 41 References .................................................................................................................................................. 42 1 Study Sites and Lead Investigators Lead Investigator Site USA 1 Judith Aberg Icahn School of Medicine at Mount Sinai, New York, NY 2 U Fritz Bredeek Metropolis Medical, San Francisco, CA 3 Robert Brennan Infectious Diseases Assoc of Central VA, Lynchburg, VA 4 Cynthia Brinson Central Texas Clinical Research, Austin, TX 5 Indira Brar Henry Ford Hospital, Detroit, MI 6 Douglas Cunningham Pueblo Family Physicians, Phoenix, AZ 7 Franco Felizarta Bakersfield, CA 8 Deborah Goldstein Whitman Walker Clinic, Washington, D.C. 9 Harold Katner Mercer University School of Medicine, Macon, GA 10 Rachel Presti Washington University School of Medicine, St. Louis, MO 11 Edgar Overton University of Alabama 1917 Clinic, Birmingham, AL 12 Alyssa Shon Evergreen Health, University of Buffalo, Buffalo, NY 13 Chris Bettacchi North Texas Infectious Disease Consultants, Dallas, TX 14 Princy Kumar Georgetown University Hospital, Washington, D.C. 15 Christopher Polk Infectious Disease Consultants, Charlotte, NC 16 Gary Simon Medical Faculty Associates, George Washington University, Washington, D.C. 17 David Wohl Medical Faculty Associates, George Washington University, Washington, D.C. 18 Mia Scott Apex Research, Denver, CO 19 Susan Swindells University of Nebraska Medical Center, Omaha, NE 20 Babafemi Taiwo Northwestern University, Chicago, IL 21 Anthony Mills Kaiser Permanente Medical Center, Los Angeles, CA 22 Peter Ruane Los Angeles, CA 23 Jerome De Vente Living Hope Clinical Foundation, Long Beach, CA 24 Margaret Hoffman-Terry Lehigh Valley Hospital, Allentown, PA 25 Chiu-Bin Hsiao Allegheny General Hospital, Pittsburgh, PA 26 Annie Luetkemeyer San Francisco General Hospital, San Francisco, CA 27 Martin Markowitz Aaron Diamond AIDS Research Center, New York, NY 28 Gerald Pierone AIDS Research & Treatment Center of the Treasure Coast, Vero Beach, FL 29 Gary Richmond Fort Lauderdale, FL 30 David Wheeler Clinical Alliance for Research & Education - Infectious Diseases, Annandale, VA 31 Carl Fichtenbaum University of Cincinnati College of Medicine, Cincinnati, OH 32 Gordon Crofoot Houston, TX 33 Hannah Olivet Community Research Initiative of New England, Boston, MA 34 Tanya Schreibman Comprehensive Care Clinic, Sarasota, FL 35 Kenneth Lichtenstein Eisenhower Medical Associates, Palm Springs, CA 2 Lead Investigator Site 36 Moti Ramgopal Fort Pierce, FL Canada 37 Jean-Guy Baril Clinique Medicale Quartier Latin, Montreal, Québec 38 Sylvie Trottier CHU de Québec Hôpital CHUL, Québec, Québec 39 Jonathan Angel The Ottawa Hospital-General Campus, Ottawa, Ontario 40 Alexander Wong Regina Qu’Appelle Health Region, Regina, Saskatchewan 41 Alexandra de Pokomandy Royal Victoria Hospital/McGill University Health Centre (MUHC), Montreal, Québec 42 Graham Smith Maple Leaf Research, Toronto, Ontario Mexico 43 Jaime-Federico Andrade- Hospital Civil de Guadalajara Fray Antonio Alcalde, Villanueva Guadalajara, Jalisco Argentina 44 Pedro Cahn Fundación Huésped, Buenos Aires 45 Isabel Cassetti Helios Salud, Buenos Aires 46 Norma Porteiro Fundación IDEAA, Buenos Aires 47 Sergio Lupo Instituto Caici, Rosario, Santa Fe France 48 Jean-Michel Molina Hôpital Saint Louis, Paris 49 Pierre Delobel Hôpital Purpan, Toulouse 50 Faïza Ajana Hôpital Gustave Dron, Tourcoing 51 Marie-Aude Khuong-Josses Hôpital Delafontaine, Saint Denis 52 Christine Katlama Hôpital de la Pitié-Salpêtrière, Paris 53 Pierre-Marie Girard Hôpital Saint Antoine, Paris 54 Yazdan Yazdanpanah Hôpital Bichat-Claude Bernard, Paris 55 Jacques Reynes Hôpital Gui de Chauliac, Montpellier Germany 56 Axel Baumgarten Zentrum für Infektiologie Berlin Prenzlauer Berg, Berlin 57 Matthias Stoll Medizinische Hochschule Hannover, Hannover 58 Juergen Rockstroh Rheinische Friedrich-Wilhelms Universitaet, Bonn 59 Christoph Stephan Klinikum der J-W-Goethe-Universitaet, Frankfurt am Main 60 Stefan Esser Universitaetsklinikum Essen, Essen 61 Thomas Lutz Infektio Research, Frankfurt 62 Hans Jaeger MUC Research GmbH, Muenchen 63 Olaf Degen Universitaetsklinikum Eppendorf, Hamburg 3 Lead Investigator Site 64 Keikawus Arasteh Epimed GmbH, Berlin 65 Hans-Juergen Stellbrink ICH Study Center, Hamburg Italy 66 Francesco Castelli Azienda Ospedaliera Spedali Civili, Brescia 67 Giuliano Rizzardini PO Ospedale Luigi Sacco - Polo Universitario, Milano Spain 68 Rafael Rubio Hospital 12 de Octubre, Madrid 69 Marisa Montes Hospital la Paz, Madrid 70 Pompeyo Viciana Hospital Universitario Virgen del Rocío, Sevilla Fernández 71 Maria Del Mar Masia Hospital General de Elche, Elche Canuto 72 Miguel Garcia Deltoro Hospital General Universitario, Valencia 73 Antonio Ocampo Hermida Complejo Hospitalario Universitario de Vigo–Hospital Álvaro Cunqueiro, Vigo 74 Manuel Castaño Hospital Carlos Haya, Malaga 75 Antonio Antela Complejo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela 76 Eugenia Negredo Puigmal Hospital Germans Trias i Pujol, Badalona 77 Josep Mallolas Hospital Clinic I Provincial De Barcelona, Barcelona 78 Hernando Knobel Hospital del Mar, Barcelona 79 Vicens Falcó Ferrer Hospital Valle d’Hebrón, Barcelona 80 Antonio Rivero Román Hospital Reina Sofía, Córdoba 81 Santiago Moreno Guillen Hospital Ramón Y Cajal, Madrid Sweden 82 Anders Thalme Karolinska Universitetssjukhuset, Huddinge, Stockholm 83 Carl Johan Treutiger Karolinska Universitetssjukhuset, Huddinge, Stockholm 84 Magnus Gisslén Sahlgrenska Universitetssjukhuset/Östra, Göteborg Russian Federation 85 Vadim Pokrovsky Central Research Institute of Epidemiology, Moscow 86 Denis Gusev St. Petersburg City AIDS Centre, St. Petersburg 87 Olga Tsybakova Smolensk Regional AIDS Centre, Smolensk 88 Svetlana Volkova Sverdlovsk Regional AIDS Center, Ekaterinburg 89 Valery Kulagin Krasnodar’s Area AIDS Centre, Krasnodar 90 Oksana Chernova Tolyatti City AIDS Centre, Tolyatti 91 Olga Borodkina Kemerovo Regional AIDS Centre, Kemerovo 4 Lead Investigator Site 92 Firaya Nagimova Tatarstan Republican AIDS Centre, Kazan 93 Olga Tonkikh Lipetsk Regional AIDS Centre, Lipetsk 94 Alexey Yakovlev City Hospital of Infectious Diseases, St. Petersburg 95 Elena Belonosova Orel Regional AIDS Centre, Orel 96 Eugene Voronin Republican Hospital of Infectious Diseases, St. Petersburg 97 Andrey Shuldyakov Saratov Regional AIDS Centre, Saratov South Africa 98 Mohammed Tayob Mzansi Ethical Research Centre, Middelburg 99 Monja-Marie Nortje Moriana Clinical Research, Brandfort 100 Johannes Jurgens Josha Research, Bloemfontein Lombaard 101 Lelanie van Zyl Syzygy Clinical Research Services, Pretoria 102
Load more

Recommended publications
  • Allosteric Integrase Inhibitor Potency Is Determined Through the Inhibition of HIV-1 Particle Maturation
    Allosteric integrase inhibitor potency is determined through the inhibition of HIV-1 particle maturation Kellie A. Juradoa, Hao Wanga, Alison Slaughterb, Lei Fengb, Jacques J. Kesslb, Yasuhiro Koha, Weifeng Wanga, Allison Ballandras-Colasa, Pratiq A. Patelc, James R. Fuchsc, Mamuka Kvaratskheliab, and Alan Engelmana,1 aDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, MA 02215; and bCenter for Retrovirus Research and Comprehensive Cancer Center and cDivision of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH 43210 Edited by Alan R. Rein, National Cancer Institute, Frederick, MD, and accepted by the Editorial Board April 1, 2013 (received for review January 14, 2013) Integration is essential for HIV-1 replication, and the viral integrase HIV-1 preferentially integrates along the bodies of active genes (IN) protein is an important therapeutic target. Allosteric IN inhib- (6), a trait that is largely attributable to an interaction between itors (ALLINIs) that engage the IN dimer interface at the binding site IN and the host protein lens epithelium-derived growth factor for the host protein lens epithelium-derived growth factor (LEDGF)/ (LEDGF)/transcriptional coactivator p75 (reviewed in refs. 7 and transcriptional coactivator p75 are an emerging class of small mole- 8). LEDGF/p75 functions as a bimodal tether during integration: cule antagonists. Consistent with the inhibition of a multivalent drug elements within its N-terminal region confer constitutive binding to target, ALLINIs display steep antiviral dose–response curves ex vivo. chromatin, whereas a downstream IN-binding domain (IBD) binds ALLINIs multimerize IN protein and concordantly block its assembly lentiviral IN proteins (9, 10).
    [Show full text]
  • An Anti-Cancer Binary System Activated by Bacteriophage HK022 Integrase
    bioRxiv preprint doi: https://doi.org/10.1101/147736; this version posted June 12, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. An anti-cancer binary system activated by bacteriophage HK022 Integrase Amer Elias, Itay Spector1, Natasha Gritsenko, Yael Zilberstein2, Rena Gorovits3, Gali Prag, Mikhail Kolot* Department of Biochemistry and Molecular Biology, Tel-Aviv University, Tel-Aviv 69978, Israel 1 Histospeck, Rishon LeZion PO Box: 75321, Israel 2 Sackler cellular & molecular imaging center, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 69978, Israel 3 Institute of Plant Sciences and Genetics in Agriculture, Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 76100, Israel *Corresponding author: Mikhail Kolot Tel-Aviv University Department of Biochemistry & Molecular Biology Tel-Aviv 69978 Israel Tel.: +972-3-6406695 Fax: +972-3-6406834 E-mail: [email protected] Key words: DTA toxin, cancer therapy, binary system, site-specific recombination, bacteriophage HK022; Integrase, lung cancer, gene delivery 1 bioRxiv preprint doi: https://doi.org/10.1101/147736; this version posted June 12, 2017. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ABSTRACT Cancer gene therapy is a great promising tool for cancer therapeutics due to the specific targeting based on the cancerous gene expression background. Binary systems based on site- specific recombination are one of the most effective potential approaches for cancer gene therapy.
    [Show full text]
  • 693.Full.Pdf
    Vol. 4, 693-696, Marc/i /998 Clinical Cancer Research 693 Inhibition of Cell Growth and Telomerase Activity of Breast Cancer Cells in Vitro by 3’-Azido-3’-deoxythymidine1 Stella M. Melana, James F. Holland, and target for cancer treatment (9). Recently, the effect of AZT on Beatriz G-T. Pogo2 Chinese hamster ovary cells that display telomerase activity was investigated. AZT was preferentially incorporated into telomeric Department of Medicine, Division of Neoplastic Diseases [S. M. M.. J. F. H.. B. G-T. P.]. and Department of Microbiology [B. G-T. P.]. DNA and Z-DNA-containing regions (2). AZT. alone or in Mount Sinai School of Medicine, New York, New York 10029 combination with other antimetabolites, also inhibited the growth of human bladder cancer and colon cancer cell lines (10). Furthermore, AZT was shown to cause progressive te- ABSTRACT lomere shortening in immortalized B and T human lymphocytic The effect of zidovudine (3’-azido-3’-deoxythymidine; cell lines ( 1 1 ). Taken together. these results have stimulated AZT) was investigated in four breast cancer cell lines, a T4 further research on the effect of AZT on cancer cells. We have, cell leukemia, and a normal breast cell line in vitro. AZT therefore, investigated the effect of AZT on breast cancer cells inhibited the growth of all tumoral cell lines, but it did so in that possess tebomerase activity. The results indicated that AZT a wide range of concentrations. The growth of a normal inhibits breast cancer cell growth. anchorage-independent breast cell line was also inhibited, although it required a growth.
    [Show full text]
  • Distribution of Prophages in the Oenococcus Oeni Species
    microorganisms Article Distribution of Prophages in the Oenococcus oeni Species Olivier Claisse , Amel Chaïb, Fety Jaomanjaka ,Cécile Philippe, Yasma Barchi, Patrick M. Lucas and Claire Le Marrec * Unité de Recherche Œnologie, Bordeaux INP, University of Bordeaux, INRAE, ISVV, F-33882 Bordeaux, France; [email protected] (O.C.); [email protected] (A.C.); [email protected] (F.J.); [email protected] (C.P.); [email protected] (Y.B.); [email protected] (P.M.L.) * Correspondence: [email protected]; Tel.: +33-557-575-831 Abstract: Oenococcus oeni is the most exploited lactic acid bacterium in the wine industry and drives the malolactic fermentation of wines. Although prophage-like sequences have been identified in the species, many are not characterized, and a global view of their integration and distribution amongst strains is currently lacking. In this work, we analyzed the complete genomes of 231 strains for the occurrence of prophages, and analyzed their size and positions of insertion. Our data show the limited variation in the number of prophages in O. oeni genomes, and that six sites of insertion within the bacterial genome are being used for site-specific recombination. Prophage diversity patterns varied significantly for different host lineages, and environmental niches. Overall, the findings highlight the pervasive presence of prophages in the O. oeni species, their role as a major source of within-species bacterial diversity and drivers of horizontal gene transfer. Our data also have implications for enhanced understanding of the prophage recombination events which occurred during evolution of O. oeni, as well as the potential of prophages in influencing the fitness of these bacteria in their distinct niches.
    [Show full text]
  • Intestinal Virome Changes Precede Autoimmunity in Type I Diabetes-Susceptible Children,” by Guoyan Zhao, Tommi Vatanen, Lindsay Droit, Arnold Park, Aleksandar D
    Correction MEDICAL SCIENCES Correction for “Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children,” by Guoyan Zhao, Tommi Vatanen, Lindsay Droit, Arnold Park, Aleksandar D. Kostic, Tiffany W. Poon, Hera Vlamakis, Heli Siljander, Taina Härkönen, Anu-Maaria Hämäläinen, Aleksandr Peet, Vallo Tillmann, Jorma Ilonen, David Wang, Mikael Knip, Ramnik J. Xavier, and Herbert W. Virgin, which was first published July 10, 2017; 10.1073/pnas.1706359114 (Proc Natl Acad Sci USA 114: E6166–E6175). The authors wish to note the following: “After publication, we discovered that certain patient-related information in the spreadsheets placed online had information that could conceiv- ably be used to identify, or at least narrow down, the identity of children whose fecal samples were studied. The article has been updated online to remove these potential privacy concerns. These changes do not alter the conclusions of the paper.” Published under the PNAS license. Published online November 19, 2018. www.pnas.org/cgi/doi/10.1073/pnas.1817913115 E11426 | PNAS | November 27, 2018 | vol. 115 | no. 48 www.pnas.org Downloaded by guest on September 26, 2021 Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children Guoyan Zhaoa,1, Tommi Vatanenb,c, Lindsay Droita, Arnold Parka, Aleksandar D. Kosticb,2, Tiffany W. Poonb, Hera Vlamakisb, Heli Siljanderd,e, Taina Härkönend,e, Anu-Maaria Hämäläinenf, Aleksandr Peetg,h, Vallo Tillmanng,h, Jorma Iloneni, David Wanga,j, Mikael Knipd,e,k,l, Ramnik J. Xavierb,m, and
    [Show full text]
  • Virus Replication Cycles
    © Jones and Bartlett Publishers. NOT FOR SALE OR DISTRIBUTION A scanning electron micrograph of Ebola virus particles. Ebola virus contains an RNA genome. It causes Ebola hemorrhagic fever, which is a severe and often fatal disease in hu- mans and nonhuman primates. CHAPTER Virus Replication Cycles OUTLINE 3.1 One-Step Growth Curves 3.3 The Error-Prone RNA Polymerases: 3 3.2 Key Steps of the Viral Replication Genetic Diversity Cycle 3.4 Targets for Antiviral Therapies In the struggle for survival, the ■ 1. Attachment (Adsorption) ■ RNA Virus Mutagens: A New Class “ ■ 2. Penetration (Entry) of Antiviral Drugs? fi ttest win out at the expense of ■ 3. Uncoating (Disassembly and Virus File 3-1: How Are Cellular Localization) their rivals because they succeed Receptors Used for Viral Attachment ■ 4. Types of Viral Genomes and Discovered? in adapting themselves best to Their Replication their environment. ■ 5. Assembly Refresher: Molecular Biology ” ■ 6. Maturation Charles Darwin ■ 7. Release 46 229329_CH03_046_069.indd9329_CH03_046_069.indd 4466 11/18/08/18/08 33:19:08:19:08 PPMM © Jones and Bartlett Publishers. NOT FOR SALE OR DISTRIBUTION CASE STUDY The campus day care was recently closed during the peak of the winter fl u season because many of the young children were sick with a lower respiratory tract infection. An email an- nouncement was sent to all students, faculty, and staff at the college that stated the closure was due to a metapneumovirus outbreak. The announcement briefed the campus com- munity with information about human metapneumonoviruses (hMPVs). The announcement stated that hMPV was a newly identifi ed respiratory tract pathogen discovered in the Netherlands in 2001.
    [Show full text]
  • Remdesivir for the Treatment of Covid-19 — Preliminary Report
    The new england journal of medicine Original Article Remdesivir for the Treatment of Covid-19 — Preliminary Report J.H. Beigel, K.M. Tomashek, L.E. Dodd, A.K. Mehta, B.S. Zingman, A.C. Kalil, E. Hohmann, H.Y. Chu, A. Luetkemeyer, S. Kline, D. Lopez de Castilla, R.W. Finberg, K. Dierberg, V. Tapson, L. Hsieh, T.F. Patterson, R. Paredes, D.A. Sweeney, W.R. Short, G. Touloumi, D.C. Lye, N. Ohmagari, M. Oh, G.M. Ruiz-Palacios, T. Benfield, G. Fätkenheuer, M.G. Kortepeter, R.L. Atmar, C.B. Creech, J. Lundgren, A.G. Babiker, S. Pett, J.D. Neaton, T.H. Burgess, T. Bonnett, M. Green, M. Makowski, A. Osinusi, S. Nayak, and H.C. Lane, for the ACTT-1 Study Group Members*​​ ABSTRACT BACKGROUND Although several therapeutic agents have been evaluated for the treatment of coro- The authors’ full names, academic de- navirus disease 2019 (Covid-19), none have yet been shown to be efficacious. grees, and affiliations are listed in the Ap- pendix. Address reprint requests to Dr. METHODS Beigel at the National Institute of Allergy and Infectious Diseases, National Insti- We conducted a double-blind, randomized, placebo-controlled trial of intravenous tutes of Health, 5601 Fishers Ln., Rm. remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory 7E60, MSC 9826, Rockville, MD 20892- tract involvement. Patients were randomly assigned to receive either remdesivir 9826, or at jbeigel@ niaid . nih . gov. (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional *A complete list of members of the ACTT-1 Study Group is provided in the days) or placebo for up to 10 days.
    [Show full text]
  • Virtual CROI 2021 Schedule at a Glance Version 3 (Short)
    virtual CROI 2021 Schedule at a Glance Version 3 (Short) LIVE PROGRAM TIME SATURDAY, MARCH 6, 2021 SUNDAY, MARCH 7, 2021 10:00 AM W-1 PROGRAM COMMITTEE WORKSHOP FOR NEW INVESTIGATORS AND TRAINEES OPENING SESSION (10:00 – 12:05) EST (10:00 – 14:00) CHAIRS WELCOME TO virtual CROI 2021 START Conveners: Serena S. Spudich and Nicolas Chomont Chairs: Sharon L. Hillier, James A. Hoxie, and Elaine J. Abrams ADVANCES IN MOLECULAR VIROLOGY OF HIV AND SARS-CoV-2 MARTIN DELANEY PRESENTATION LIVE PROGRAM Frank Kirchhoff INTRODUCTION ADVANCES IN HIV AND SARS-CoV-2 IMMUNOLOGY James Pickett Galit Alter VACCINE NATIONALISM IS KILLING US: HOW INEQUITIES IN RESEARCH AND ACCESS TO SARS-CoV-2 VACCINES WILL PERPETUATE THE PANDEMIC ADVANCES IN COVID-19 TREATMENT STRATEGIES AND CONTROLLING THE EPIDEMIC Gregg S. Gonsalves and Fatima Hassan Jürgen Rockstroh BERNARD FIELDS LECTURE ADVANCES IN BIOMEDICAL PREVENTION OF HIV INTRODUCTION Jean-Michel Molina James A. Hoxie and Galit Alter ADVANCES IN HIV CURE NEUTRALIZING ANTIBODIES AGAINST CORONAVIRUSES Katherine J. Bar Pamela J. Bjorkman N'GALY-MANN LECTURE INTRODUCTION Elaine J. Abrams and Tedros Adhanom Ghebreyesus LESSONS FROM THE CONCURRENT HIV/AIDS AND COVID-19 PANDEMICS: A TWO-WAY STREET Anthony S. Fauci 12:20 PM CONCURRENT WORKSHOPS (12:20 – 2:20) EST W-2 FRONTIERS IN LABORATORY TECHNOLOGIES Conveners: Galit Alter and Frank Kirchhoff STRUCTURES OF SARS-CoV-2 ANTIBODIES INDUCED BY INFECTION AND mRNA VACCINES Christopher O. Barnes EMERGING CONCEPTS IN HIV-1 RESTRICTION Edward Campbell SARS-CoV-2 SPECIFIC AND CROSS-REACTIVE T CELL RESPONSES Daniela Weiskopf ARTIFICIAL INTELLIGENCE-INSPIRED ANTIBODY ENGINEERING Sai Reddy W-3 CLINICAL TRIAL DESIGN AND ANALYSIS Conveners: Susan P.
    [Show full text]
  • Cryo-EM Reveals a Novel Octameric Integrase Structure for Β-Retroviral
    HHS Public Access Author manuscript Author ManuscriptAuthor Manuscript Author Nature. Manuscript Author Author manuscript; Manuscript Author available in PMC 2016 August 18. Published in final edited form as: Nature. 2016 February 18; 530(7590): 358–361. doi:10.1038/nature16955. Cryo-EM reveals a novel octameric integrase structure for β- retroviral intasome function Allison Ballandras-Colas1, Monica Brown2, Nicola J. Cook3, Tamaria G. Dewdney1, Borries Demeler4, Peter Cherepanov3,5, Dmitry Lyumkis2, and Alan N. Engelman1 1Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, 450 Brookline Avenue, Boston, Massachusetts 02215 USA 2Laboratory of Genetics and Helmsley Center for Genomic Medicine, The Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, California 92037, USA 3Clare Hall Laboratories, The Francis Crick Institute, Blanche Lane, South Mimms EN6 3LD, UK 4Department of Biochemistry, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA 5Division of Medicine, Imperial College London, St.-Mary’s Campus, Norfolk Place, London W2 1PG, UK Abstract Retroviral integrase (IN) catalyzes the integration of viral DNA (vDNA) into host target (tDNA), which is an essential step in the lifecycle of all retroviruses1. Prior structural characterization of IN-vDNA complexes, or intasomes, from the spumavirus prototype foamy virus (PFV) revealed a functional IN tetramer2–5, and it is generally believed that intasomes derived from other retroviral genera will employ tetrameric IN6–9. However, the intasomes of orthoretroviruses, which include all known pathogenic species, have not been characterized structurally. Using single-particle cryo- electron microscopy (cryo-EM) and X-ray crystallography, we determine here an unexpected octameric IN architecture for the β-retrovirus mouse mammary tumor virus (MMTV) intasome.
    [Show full text]
  • Drosophila: Retrotransposons Making up Telomeres
    Review Drosophila: Retrotransposons Making up Telomeres Elena Casacuberta Institute of Evolutionary Biology, IBE, CSIC—Pompeu Fabra University, Barcelona Spain, Passeig de la Barceloneta 37‐49, 08003 Barcelona, Spain; [email protected]‐csic.es; Tel.: +34‐932309637; Fax: +34‐932309555 Guest Editors: Paul M. Liebermann and Benedikt B. Kaufer Received: 9 June 2017; Accepted: 17 July 2017; Published: 19 July 2017 Abstract: Drosophila and extant species are the best‐studied telomerase exception. In this organism, telomere elongation is coupled with targeted retrotransposition of Healing Transposon (HeT‐A) and Telomere Associated Retrotransposon (TART) with sporadic additions of Telomere Associated and HeT‐A Related (TAHRE), all three specialized non‐Long Terminal Repeat (non‐LTR) retrotransposons. These three very special retroelements transpose in head to tail arrays, always in the same orientation at the end of the chromosomes but never in interior locations. Apparently, retrotransposon and telomerase telomeres might seem very different, but a detailed view of their mechanisms reveals similarities explaining how the loss of telomerase in a Drosophila ancestor could successfully have been replaced by the telomere retrotransposons. In this review, we will discover that although HeT‐A, TART, and TAHRE are still the only examples to date where their targeted transposition is perfectly tamed into the telomere biology of Drosophila, there are other examples of retrotransposons that manage to successfully integrate inside and at the end of telomeres. Because the aim of this special issue is viral integration at telomeres, understanding the base of the telomerase exceptions will help to obtain clues on similar strategies that mobile elements and viruses could have acquired in order to ensure their survival in the host genome.
    [Show full text]
  • Consolidated List of Up-Regulated Proteins Expressed at Different Cr (VI) Concentrations at Time Points
    Electronic Supplementary Material (ESI) for Metallomics.
    [Show full text]
  • Graphene-VP40 Interactions and Potential Disruption of the Ebola Virus Matrix Filaments
    CORE Metadata, citation and similar papers at core.ac.uk Provided by IUPUIScholarWorks ACCEPTED MANUSCRIPT Graphene-VP40 interactions and potential disruption of the Ebola virus matrix filaments Jeevan B. GC1, Rudramani Pokhrel1, Nisha Bhattarai1, Kristen A. Johnson2, Bernard S. Gerstman1,3, Robert V. Stahelin2,4,5, Prem P. Chapagain1,3* 1Department of Physics, Florida International University, Miami, FL 33199, 2Department of Chemistry and Biochemistry, The Eck Institute for Global Health and The Boler- Parseghian Center for Rare and Neglected Diseases, University of Notre Dame, Notre Dame, IN 46556, 3Biomolecular Sciences Institute, Florida International University, Miami, FL 33199, 4Department of Biochemistry and Molecular Biology, Indiana University School of Medicine- South Bend, South Bend, IN 46617. 5Current address: Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, IN 47907. Abstract Ebola virus infections cause hemorrhagic fever that often results in very high fatality rates. In addition to exploring vaccines, developmentMANUSCRIPT of drugs is also essential for treating the disease and preventing the spread of the infection. The Ebola virus matrix protein VP40 exists in various conformational and oligomeric forms and is a potential pharmacological target for disrupting the virus life-cycle. Here we explored graphene-VP40 interactions using molecular dynamics simulations and graphene pelleting assays. We found that graphene sheets associate strongly with VP40 at various interfaces. We also found that the graphene is able to disrupt the C-terminal domain (CTD-CTD) interface of VP40 hexamers. This VP40 hexamer-hexamer interface is crucial in forming the Ebola viral matrix and disruption of this interface may provide a method to use graphene or similar nanoparticle based solutions as a disinfectant that can significantly reduce the spread of the disease and prevent an Ebola epidemic.
    [Show full text]