2017 HIV/AIDS Medicines in Development
Total Page：16
File Type：pdf, Size：1020Kb
Load more
Recommended publications
-
Review CCR5 Antagonists: Host-Targeted Antivirals for the Treatment of HIV Infection
Antiviral Chemistry & Chemotherapy 16:339–354 Review CCR5 antagonists: host-targeted antivirals for the treatment of HIV infection Mike Westby* and Elna van der Ryst Pfizer Global R&D, Kent, UK *Corresponding author: Tel: +44 1304 649876; Fax: +44 1304 651819; E-mail: [email protected] The human chemokine receptors, CCR5 and suggest that these compounds have a long plasma CXCR4, are potential host targets for exogenous, half-life and/or prolonged CCR5 occupancy, which small-molecule antagonists for the inhibition of may explain the delay in viral rebound observed HIV-1 infection. HIV-1 strains can be categorised by following compound withdrawal in short-term co-receptor tropism – their ability to utilise CCR5 monotherapy studies. A switch from CCR5 to (CCR5-tropic), CXCR4 (CXCR4-tropic) or both (dual- CXCR4 tropism occurs spontaneously in approxi- tropic) as a co-receptor for entry into susceptible mately 50% of HIV-infected patients and has been cells. CCR5 may be the more suitable co-receptor associated with, but is not required for, disease target for small-molecule antagonists because a progression. The possibility of a co-receptor natural deletion in the CCR5 gene preventing its tropism switch occurring under selection pressure expression on the cell surface is not associated by CCR5 antagonists is discussed. The completion with any obvious phenotype, but can confer of ongoing Phase IIb/III studies of maraviroc, resistance to infection by CCR5-tropic strains – the aplaviroc and vicriviroc will provide further insight most frequently sexually-transmitted strains. into co-receptor tropism, HIV pathogenesis and The current leading CCR5 antagonists in clinical the suitability of CCR5 antagonists as a potent development include maraviroc (UK-427,857, new class of antivirals for the treatment of HIV Pfizer), aplaviroc (873140, GlaxoSmithKline) and infection. -
Product Monograph for CELSENTRI
PRODUCT MONOGRAPH PrCELSENTRI maraviroc Tablets 150 and 300 mg CCR5 antagonist ViiV Healthcare ULC 245, boulevard Armand-Frappier Laval, Quebec H7V 4A7 Date of Revision: July 05, 2019 Submission Control No: 226222 © 2019 ViiV Healthcare group of companies or its licensor. Trademarks are owned by or licensed to the ViiV Healthcare group of companies. Page 1 of 60 Table of Contents PART I: HEALTH PROFESSIONAL INFORMATION.........................................................3 SUMMARY PRODUCT INFORMATION ........................................................................3 INDICATIONS AND CLINICAL USE..............................................................................3 CONTRAINDICATIONS ...................................................................................................3 WARNINGS AND PRECAUTIONS..................................................................................4 ADVERSE REACTIONS....................................................................................................9 DRUG INTERACTIONS ..................................................................................................19 DOSAGE AND ADMINISTRATION..............................................................................28 OVERDOSAGE ................................................................................................................31 ACTION AND CLINICAL PHARMACOLOGY ............................................................31 STORAGE AND STABILITY..........................................................................................36 -
Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis
Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis Centers for Disease Control and Prevention Office of Infectious Diseases National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination June 2013 This document is accessible online at http://www.cdc.gov/tb/TB_HIV_Drugs/default.htm Suggested citation: CDC. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis [online]. 2013. Available from URL: http://www.cdc.gov/tb/TB_HIV_Drugs/default.htm Table of Contents Introduction 1 Methodology for Preparation of these Guidelines 2 The Role of Rifamycins in Tuberculosis Treatment 4 Managing Drug Interactions with Antivirals and Rifampin 5 Managing Drug Interactions with Antivirals and Rifabutin 9 Treatment of Latent TB Infection with Rifampin or Rifapentine 10 Treating Pregnant Women with Tuberculosis and HIV Co-infection 10 Treating Children with HIV-associated Tuberculosis 12 Co-treatment of Multidrug-resistant Tuberculosis and HIV 14 Limitations of these Guidelines 14 HIV-TB Drug Interaction Guideline Development Group 15 References 17 Table 1a. Recommendations for regimens for the concomitant treatment of tuberculosis and HIV infection in adults 21 Table 1b. Recommendations for regimens for the concomitant treatment of tuberculosis and HIV infection in children 22 Table 2a. Recommendations for co-administering antiretroviral drugs with RIFAMPIN in adults 23 Table 2b. Recommendations for co-administering antiretroviral drugs with RIFAMPIN in children 25 Table 3. Recommendations for co-administering antiretroviral drugs with RIFABUTIN in adults 26 ii Introduction Worldwide, tuberculosis is the most common serious opportunistic infection among people with HIV infection. -
Cytokines and Chemokines in SARS-Cov-2 Infections—Therapeutic Strategies Targeting Cytokine Storm
biomolecules Review Cytokines and Chemokines in SARS-CoV-2 Infections—Therapeutic Strategies Targeting Cytokine Storm Alexandra Pum 1, Maria Ennemoser 1, Tiziana Adage 2 and Andreas J. Kungl 1,3,* 1 Institute Of Pharmaceutical Sciences, Karl-Franzens-University Graz, Schubertstrasse 1, 8010 Graz, Austria; [email protected] (A.P.); [email protected] (M.E.) 2 Brain Implant Therapeutics (BIT) Pharma, Leonhardstrasse 109, 8010 Graz, Austria; [email protected] 3 Antagonis Biotherapeutics GmbH, Strasserhofweg 77, 8045 Graz, Austria * Correspondence: [email protected] Abstract: The recently identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, the cause of coronavirus disease (COVID-19) and the associated ongoing pandemic, frequently leads to severe respiratory distress syndrome and pneumonia with fatal consequences. Although several factors of this infection and its consequences are not completely clear, the presence and involvement of specific chemokines is undoubtedly crucial for the development and progression of COVID-19. Cytokine storm and the often-resulting cytokine release syndrome (CRS) are patho- physiological hallmarks in COVID-19 infections related to its most severe and fatal cases. In this hyperinflammatory event, chemokines and other cytokines are highly upregulated and are therefore not fulfilling their beneficial function in the host response anymore but causing harmful effects. Here, we present the recent views on the involvement of chemokines and selected cytokines in COVID-19 and the therapeutics currently in clinical development targeting or interfering with them, discussing their potentials in the treatment of COVID-19 infections. Keywords: chemokines; SARS-CoV-2; COVID-19; coronavirus; cytokine storm Citation: Pum, A.; Ennemoser, M.; Adage, T.; Kungl, A.J. -
Therapeutic Guidelines for Antiretroviral (ARV) Treatment of Adult HIV Infection September 2015
Therapeutic Guidelines for Antiretroviral (ARV) Treatment of Adult HIV Infection September 2015 Prepared by J Montaner (editor), S Guillemi and M Harris (co-editors) on behalf of the Committee for Drug Evaluation and Therapy, British Columbia Centre for Excellence in HIV/AIDS The BC-CfE Therapeutic Guidelines have remained generally consistent but not identical with the IAS-USA Guidelines since 1996. The current Guidelines are consistent with those published by H.F. Günthard et al. in 2014 (Günthard HF, Aberg JA, Eron JJ, et al. Antiretroviral Treatment of Adult HIV Infection: 2014 Recommendations of the International Antiviral Society–USA Panel. JAMA 2014; 312(4):410-425). However, the reader should be aware that the use of antiretroviral drugs for the treatment of HIV infection within the BC-CfE programs is exclusively guided by the 2015 Guidelines as outlined here. BC-CfE 2015 ARV Guidelines Page: 2 Committee for Drug Evaluation and Therapy of the BC Centre for Excellence in HIV/AIDS Co-chairs Rolando Barrios Val Montessori Committee Members Linda Akagi Silvia Guillemi Marianne Harris Robert Hogg Mark Hull Deborah Money David Moore Peter Phillips Neora Pick BC-CfE 2015 ARV Guidelines Page: 3 TABLE OF CONTENTS Glossary of abbreviations……………………………………………………………………….….…………….5 I. Summary…………………………………………….…………………………………………………….……...………7 II. Introduction…………………………………………………………………………………………………..……….…9 III. When to start…………………………………………………………………………………………………………..10 A. Recommendations ……………………………………………………………………………………………10 B. Evidence…………………………………………………………………………………………………….……..10 -
Case Series of Four Critically Ill Patients Treated with Leronlimab --Manuscript Draft
Journal of Translati onal Autoimmunity Disruption of CCR5 Signaling to Treat COVID-19-Associated Cytokine Storm: Case Series of Four Critically Ill Patients Treated with Leronlimab --Manuscript Draft-- Manuscript Number: JTAUTO-D-20-00043R1 Full Title: Disruption of CCR5 Signaling to Treat COVID-19-Associated Cytokine Storm: Case Series of Four Critically Ill Patients Treated with Leronlimab Article Type: Review Article Keywords: Leronlimab, Acute respiratory distress syndrome, monoclonal antibody, Cytokine storm, treatment, CCR5 Corresponding Author: Nicholas Agresti, M.D. Southeast Georgia Health System Inc Brunswick, Georgia UNITED STATES Corresponding Author Secondary Information: Corresponding Author's Institution: Southeast Georgia Health System Inc Corresponding Author's Secondary Institution: First Author: Nicholas Agresti, M.D. First Author Secondary Information: Order of Authors: Nicholas Agresti, M.D. Jay Lelazari, MD Phillip Amodeo, MD Kabir Mody, MD Stephen Mosher, MD Harish Seethamraju, MD Scott Kelly, MD Nader Pourhassan, PhD David Sudduth, MD Christopher Bovinet, MD Mohammed Elsharkawi, MD Bruce K Patterson, MD Reejis Stephens, MD Jonah Sacha, PhD Helen Wu, PhD Seth Gross, MD FACG Kush Dhody, MBBS, MS, CCRA Order of Authors Secondary Information: Manuscript Region of Origin: UNITED STATES Abstract: The trafficking of inflammatory cells into the lungs of patients with SARS-Cov-2 and ARDS appears to be controlled by signaling through the CCR1 and/ or the CCR5 pathways. We report the first case series of critically ill patients with SARS-Cov-2 successfully treated with leronlimab, a monoclonal antibody which binds to the CCR5 Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation receptor found on T cells and macrophages. -
Overview on Chemokine Co-Receptor-5 (CCR-5) HIV-1 Entry
Pant et al Journal of Drug Delivery & Therapeutics. 2018; 8(4):73-79 Available online on 15.07.2018 at jddtonline.info Journal of Drug Delivery and Therapeutics Open Access to Pharmaceutical and Medical Research © 2011-18, publisher and licensee JDDT, This is an Open Access article which permits unrestricted non- commercial use, provided the original work is properly cited Open Access Review Article Overview on Chemokine Co-Receptor-5 (CCR-5) HIV-1 Entry Inhibitors Pant Kavita*, Singh Anita Department of Pharmaceutical Sciences, Kumaun University Campus Bhimtal, Nainital-263136, Uttarakhand, India ABSTRACT In the 21st century, HIV-1 has turned into a noteworthy global challenge in medication. As per WHO report 2017, HIV is one of the deadliest diseases adding to an aggregate of 36.7 million contaminations until December 2016 among which 1.8 million were analyzed in 2016 itself. In 2016, 19.5 million individuals experienced to anti-retroviral treatment summing up to US$ 11 billion. With regards to rising resistance from anti-retroviral medication in HIV treatment, the advancement of most recent medication classes with a newer mode of action stays essential. The CCR5 co-receptor inhibitors suppress the fusion of HIV with the host cell by upsetting the connection of gp-120 protein with the CCR5 receptor. Though severalCCR5 antagonists are assessed in clinical trials, just Maraviroc has been endorsed for clinical use in the treatment of HIV infected patients. The efficacy and safety profile of CCR5 adversaries with a consideration on maraviroc are assessed here in conjunction with their use in newer and developing clinical trials. -
CCR2/CCR5-Mediated Macrophage–Smooth Muscle Cell Crosstalk in Pulmonary Hypertension
ORIGINAL ARTICLE PULMONARY HYPERTENSION AND BASIC SCIENCE CCR2/CCR5-mediated macrophage– smooth muscle cell crosstalk in pulmonary hypertension Shariq Abid1,2, Elisabeth Marcos1,2, Aurélien Parpaleix1,2, Valérie Amsellem1,2, Marielle Breau1,2, Amal Houssaini1,2, Nora Vienney1,2, Marine Lefevre3, Genevieve Derumeaux1,2, Steven Evans4, Cedric Hubeau4, Marion Delcroix 5, Rozenn Quarck5, Serge Adnot1,2 and Larissa Lipskaia1,2 Affiliations: 1INSERM U955, Département de Physiologie, Hôpital Henri Mondor, AP-HP, DHU A-TVB, Créteil, France. 2Université Paris-Est Créteil (UPEC), Créteil, France. 3Departement Anatomopathologie, Institut Mutualiste Montsouris, Paris, France. 4Inflammation and Immunology Research Unit, Pfizer Worldwide Research and Development, Cambridge, MA, USA. 5Respiratory Division, University Hospitals of Leuven and Dept of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium. Correspondence: Serge Adnot, Hôpital Henri Mondor, Service de Physiologie-Explorations Fonctionnelles, 94010, Créteil, France. E-mail: [email protected] @ERSpublications CCR2 and CCR5 are required for collaboration between macrophages and pulmonary artery smooth muscle cells (PASMCs) to initiate and amplify PASMC proliferation. Dual targeting of CCR2 and CCR5 may hold promise for treating pulmonary artery hypertension. http://bit.ly/2L3izU6 Cite this article as: Abid S, Marcos E, Parpaleix A, et al. CCR2/CCR5-mediated macrophage–smooth muscle cell crosstalk in pulmonary hypertension. Eur Respir J 2019; 54: 1802308 [https://doi.org/10.1183/ 13993003.02308-2018]. ABSTRACT Macrophages are major players in the pathogenesis of pulmonary arterial hypertension (PAH). To investigate whether lung macrophages and pulmonary-artery smooth muscle cells (PASMCs) collaborate to stimulate PASMC growth and whether the CCL2-CCR2 and CCL5-CCR5 pathways inhibited macrophage–PASMC interactions and PAH development, we used human CCR5-knock-in mice and PASMCs from patients with PAH and controls. -
Small Molecules
www.adipogen.com INFLAMMATION Small Molecules Inflammasome Reagents 2 TLR Agonists & Antagonists 3 Antiviral & Anti-inflammatory Reagents 4 HIGHLIGHTS Potent Immunosuppressors 4 Antimicrobial Compounds 5 METABOLIC RESEARCH AMPK Modulators 6 Synthetic Small Molecules PPAR Agonists 7 Energy Metabolism Modulators 8 Cardiovascular Reagents 9 Other Metabolic Research Reagents 9 Unique Natural Products CANCER & IMMUNOLOGY Autophagy Modulators Overview 10 PP2A Inhibitors 10 Proteasome Inhibitors 11 PI3K Inhibitors & mTOR Modulators 12 Protein Kinase Modulators 13 Rare Antibiotics Microtubule & F-Actin Modulators 14 H+-V-ATPase Inhibitors 14 Angiogenesis (VEGF) Modulators 15 Potent iNKT Stimulators 16 Gangliosides 16 manufactured in switzerland Sonic Hedgehog Modulators 17 Farnesyltransferase Inhibitors 17 Ubiquitin Related Inhibitors 17 Selected Anticancer Compounds 18 HDAC & HAT Inhibitors 19 Caspase Inhibitors 19 Antioxidants, ROS, NO and H2S 19 Full Panel of >1500 Small Molecules NEUROCHEMICALS Over 25 Years of Experience Receptor Agonists & Antagonists 20 High-end Customer & Technical Support Neurotoxins 21 BULK Quantities Anti-neurodegenerative Diseases 21 Model Compound for Sensory Studies 21 COMMODITIES ROCK Inhibitors 22 Collaborating with: Stem Cell Modulators 22 Notch Processing Inhibitors 22 Commodity Standards 23 Probes & Dyes 24 New HDAC6 Inhibitors 24 www.adipogen.com Selected NLRP3 Inflammasome Inhibitors NEW Arglabin MCC950 . Na AG-CN2-0458 1 mg | 5 mg AG-CR1-3615 1 mg | 5 mg | 10 mg BAY 11-7082 Formula: C20H23N2NaO5S AG-CR1-0013 10 mg | 50 mg MW: 426.5 O O O Colchicine CAS: 256373-96-3 H C S 3 N N HO Na H AG-CN2-0048 500 mg | 1 g Potent and selective NLRP3 O H3C inflammasome inhibitor. Glyburide (USP) LIT: A small-molecule inhibitor of the NLRP3 inflammasome for the treatment AG-CR1-3613 1 g | 5 g | 10 g of inflammatory diseases: R.C. -
CCR5 Inhibitors And
Update On CCR5 Inhibitors: Scientific Rationale, Clinical Evidence, and Anticipated Uses In August of 2007, the Food and Drug Administration (fda) approved Binding of gp120 to its primary receptor on the cell surface, cd4, is the first chemokine c-c( motif) receptor 5 (ccr5) inhibitor, maraviroc, the first step in membrane fusion (Figure 1b). Thecd 4 binding site is not for treatment-experienced patients infected with r5-using virus. In an completely formed in unliganded gp120, but is stabilized and fixed by the effort to better educate physicians and patients about these new drugs, approach of cd4.8 After cd4 binding, sequential binding of the coreceptor this article will review the available clinical data on ccr5 antagonists and is typically the next step in the fusion process (Figure 1c). It should discuss implications for clinical practice. Chemokine receptor antagonists be noted, however, that some interactions of cd4 with gp120 lead to are the first antiretrovirals to bind a cellular protein of the host and, as inappropriate shedding of gp120 and inactivation of the fusion reaction. such, engender unique safety concerns. We will review the biology of hiv For fusion to proceed, gp120 must next bind its coreceptor, either ccr5 chemokine usage and entry into cells that first suggested the attractiveness or cxcr4. The interaction of gp120 with cd4 leads to a conformational of ccr5 blockade as a therapeutic target. We will discuss the 2 primary change that results in formation of the coreceptor binding site on gp120.9 means of ccr5 antagonism—small molecule inhibition and monoclonal Coreceptor recognition is determined by several structural elements of antibody steric blockade recognizing that, in the near future, only the small gp120 that include the v1-v2 region, the bridging sheet (an antiparallel, molecule antagonist maraviroc is fda approved for clinical use. -
Should Leronlimab (PRO 140) Be Used in the Treatment of COVID-19?
Should Leronlimab (PRO 140) be used in the treatment of COVID-19? Authors: Lylah D. Reyes, MD, MSc, Eva I. Bautista, MD, MSc] Date of Review: [13-APRIL-2020 (version #1)] Last Updated: [13-April-2020 (version # 1)] KEY FINDINGS There is no evidence that Leronlimab is an effective treatment for COVID 19. • Leronlimab (PRO 140),1 a humanized IgG4 monoclonal antibody, is an investigational drug initially indicated for treatment of HIV infection and metastatic triple-negative breast cancer (mTNBC).1 Leronlimab, a CCR5 receptor antagonist, can potentially offer therapeutic benefit by improving the immune response while abating the “cytokine storm” in COVID-19.2 • There is no available evidence that Leronlimab is an effective treatment for COVID 19. • There is limited evidence for its safety based on trials conducted for HIV.3 The commonly reported adverse events include headache, lymphadenopathy, diarrhea, fatigue, hypertension, nasal congestion and pruritus.3 • Currently, it has been granted emergency Interventional New Drug (eIND) status by FDA, targeted to treat patients with respiratory complications associated with COVID-19.2 There are two ongoing trials involving COVID-19 cases. • Leronlimab is not included in the recommended therapeutic options for COVID19 in the WHO Interim Guidance, and US CDC Clinical Interim Guidelines. Disclaimer: The aim of these rapid reviews is to retrieve, appraise, summarize and update the available evidence on COVID-related health technology. The reviews have not been externally peer-reviewed; they should not replace individual clinical judgement and the sources cited should be checked. The views expressed represent the views of the authors and not necessarily those of their host institutions. -
Cellular Senescence and Inflammaging in Age-Related Diseases
Mediators of Inflammation Cellular Senescence and Inflammaging in Age-Related Diseases Lead Guest Editor: Carmela R. Balistreri Guest Editors: Fabiola Olivieri, Johannes Grillari, and Francesco Prattichizzo Cellular Senescence and Inflammaging in Age-Related Diseases Mediators of Inflammation Cellular Senescence and Inflammaging in Age-Related Diseases Lead Guest Editor: Carmela R. Balistreri Guest Editors: Fabiola Olivieri, Johannes Grillari, and Francesco Prattichizzo Copyright © 2018 Hindawi. All rights reserved. This is a special issue published in “Mediators of Inflammation.” All articles are open access articles distributed under the Creative Com- mons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Editorial Board Anshu Agrawal, USA Antonella Fioravanti, Italy Kutty Selva Nandakumar, China Muzamil Ahmad, India Stefanie B. Flohé, Germany Hannes Neuwirt, Austria Maria Jose Alcaraz, Spain Jan Fric, Czech Republic Nadra Nilsen, Norway Simi Ali, UK Tânia Silvia Fröde, Brazil Daniela Novick, Israel Amedeo Amedei, Italy Julio Galvez, Spain Marja Ojaniemi, Finland Oleh Andrukhov, Germany Mirella Giovarelli, Italy Sandra Helena Penha Oliveira, Brazil Emiliano Antiga, Italy Denis Girard, Canada Olivia Osborn, USA Adone Baroni, Italy Ronald Gladue, USA Carla Pagliari, Brazil Jagadeesh Bayry, France Markus H. Gräler, Germany Martin Pelletier, Canada Jürgen Bernhagen, Germany Hermann Gram, Switzerland Vera L. Petricevich, Mexico Tomasz Brzozowski, Poland Francesca Granucci, Italy Sonja Pezelj-Ribarić, Croatia Philip Bufler, Germany Oreste Gualillo, Spain Phileno Pinge-Filho, Brazil Elisabetta Buommino, Italy Elaine Hatanaka, Brazil Michele T. Pritchard, USA Daniela Caccamo, Italy Nobuhiko Kamada, USA Michal A. Rahat, Israel Luca Cantarini, Italy Yoshihide Kanaoka, USA Zoltan Rakonczay Jr., Hungary Raffaele Capasso, Italy Yona Keisari, Israel Marcella Reale, Italy Calogero Caruso, Italy Alex Kleinjan, Netherlands Alexander Riad, Germany Maria Rosaria Catania, Italy Marije I.