DOCSLIB.ORG

Case Report Lamivudine Therapy for a Hepatitis B Surface Antigen

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Case Report Lamivudine Therapy for a Hepatitis B Surface Antigen Bone Marrow Transplantation (2000) 26, 1243–1245 2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt Case report Lamivudine therapy for a hepatitis B surface antigen (HBsAg)-positive leukemia patient receiving myeloablative chemotherapy and autologous stem cell transplantation N Uchida1, H Gondo1, D Himeji1, Y Kaji1, M Sata2 and Y Niho1 1First Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka; and 2Second Department of Internal Medicine, Faculty of Medicine, Kurume University, Fukuoka, Japan Summary: Case report Hepatitis B virus (HBV) can be a cause of fatal liver failure after chemotherapy for viral carrier patients and A 33-year-old Japanese man was diagnosed with acute limits the indication of myeloablative therapy for them. myelogenous leukemia (FAB classification, M2) and found We describe an HBsAg-positive leukemia patient who to be an asymptomatic carrier of HBV. After achieving successfully underwent autologous PBSC transplant. complete remission with induction chemotherapy, he After chemotherapeutic treatment his serum HBV DNA received consolidation chemotherapy twice (Figure 1).6 His level rose in association with hepatitis. To prevent pro- clinical course was uneventful until following his second gression to fulminant hepatitis, we administered lamivu- consolidation chemotherapy when HBV DNA and ALT dine, a viral reverse transcriptase inhibitor, during the levels increased to 3800 meq/ml (measured by branched transplantation procedure. The patient did not show DNA probe method7) and 217 U/l, respectively. With bed any increase of HBV DNA or a worsening of his hepa- rest only these levels decreased to normal by 3 months. titis. Thus, lamivudine may be a promising treatment Since his leukemic cells had poor prognostic karyotypes for HBsAg-positive patients receiving myeloablative (trisomy 8 and 21), the patient decided to receive an auto- chemotherapy and autologous stem cell transplantation. logous peripheral blood stem cell transplantation as further Bone Marrow Transplantation (2000) 26, 1243–1245. treatment. The pretransplant conditioning regimen con- Keywords: lamivudine; hepatitis type B; stem cell trans- sisted of busulfan, cytosine arabinoside and etoposide plantation (BEA regimen).6 Granulocyte colony-stimulating factor (G- CSF) was administered concurrently with the BEA regimen during conditioning. Lamivudine (Glaxo Wellcome Reactivation of the hepatitis B virus (HBV) and subsequent Research and Development, Greenford, UK) 100 mg/day fulminant hepatitis have been reported following myeloabl- was administered orally starting on day −1. Peripheral + ative chemotherapy and stem cell transplantation for leuke- blood stem cells (3.7 × 106 CD34 cells/kg) which had been mia patients with HBV infection.1 Interferon is effective collected during recovery after consolidation chemotherapy in approximately 30% of such patients with chronic HBV were infused on day 0. infection.2 However, adverse effects including fever, mal- Post transplantation, granulocytes exceeded 500 × 106/l aise, anorexia and depression are major concerns with inter- and platelets exceeded 20 × 109/l on days 14 and 18, feron treatment. Lamivudine is a nucleoside analogue respectively. HBV DNA or ALT levels were not elevated which specifically inhibits viral reverse transcriptase while during the therapy (Figure 1), and lamivudine adminis- suppressing HBV replication.3 A trial of lamivudine for tration was discontinued 3 months after transplantation. The chronic HBV infection has demonstrated that it signifi- patient subsequently experienced HBV DNA elevation 4 cantly reduces HBV DNA and alanine aminotransferase months later, but this was successfully treated with read- (ALT) levels.4,5 In the present study, lamivudine was ministration of lamivudine. There were no adverse effects administered to an HBsAg-positive leukemia patient to during lamivudine therapy. Lamivudine therapy was prevent progression to fulminant hepatitis following stopped when the patient suffered a relapse of his leukemia. autologous PBSC transplantation. Despite re-induction chemotherapy, the patient did not ach- ieve complete remission and died of pneumonia 3 months after relapse. HBV DNA did not become elevated and he did not develop hepatitis, even after the discontinuation Correspondence: Dr N Uchida, The Terry Fox Laboratory, 601 West 10th of lamivudine. Avenue, Vancouver, British Columbia, V5Z 1L3, Canada Received 8 May 2000; accepted 20 June 2000 Lamivudine therapy for HBV carrier in PBSC transplant N Uchida et al 1244 IDR/ MIT/ VP16/ IDR/ Ara-C Ara-C Ara-C G-CSF Ara-C 400 BU/VP16/Ara-C 300 Lamivudine 100 mg 100 mg PBSCH PBSCT relapse 200 100 Alanine aminotransferase (U/l) 0 4000 3000 2000 1000 0 HBV DNA (meq/ml) HBV DNA 1997 1998 1999 Oct Jan Oct Jan Aug Sept Nov Dec Feb April May June July Aug Sept Nov Dec March Figure 1 Chart showing serum levels of alanine aminotransferase (upper panel) and HBV DNA (lower panel) before and after lamivudine therapy. It shows clear correlation between HBV load and hepatitis which means hepatitis was caused by HBV. Lamivudine therapy kept viral load at a low level and successfully prevented acute exacerbation of hepatitis. IDR, idarubicin; MIT, mitoxantrone; VP16, etoposide; Ara-C, cytosine arabinoside; BU, busulfan; PBSCH, peripheral blood stem cell harvest; PBSCT, peripheral blood stem cell transplantation. Discussion loablative therapy and stem cell transplantation, and that a prospective study of lamivudine for stem cell transplan- Patients with HBV infection are at risk of an exacerbation tation in HBsAg-positive patients is warranted. of viral hepatitis after cytotoxic treatment.1 There are no specific markers to anticipate viral reactivation, and every patient with HBV needs to be carefully monitored during Acknowledgements chemotherapy. Lamivudine, an oral nucleoside analogue, has shown The authors wish to thank the Glaxo Wellcome Research and promise in patients with chronic hepatitis B.3 It inhibits Development (Greenford, UK) for kindly providing lamivudine. viral reverse transcriptase and suppresses viral replication. It has also recently been reported that this drug is also use- ful for the treatment of viral hepatitis after cytotoxic ther- References apy.8,9 In the present patient lamivudine appeared to work to not only avoid HBV exacerbation during transplantation, 1 Lau GKK, Liang R, Chiu EKW et al. Hepatic events after but also to treat reactivation of HBV later. bone marrow transplantation in patients with hepatitis B infec- Lamivudine can be administered without significant tion: a case controlled study. Bone Marrow Transplant 1997; adverse effects, but one of the concerns with this treatment 19: 795–799. is the emergence of viral mutants. A trial of lamivudine 2 Perrillo RP. Treatment of chronic hepatitis B with interferon: for chronic HBV infection has demonstrated that long-term experience in Western countries. Semin Liver Dis 1989; 9: usage of this drug is associated with HBV tyrosine-meth- 240–248. 3 Doong SL, Tsai CH, Schinazi RF et al. Inhibition of the repli- ionine-aspartate-aspartate (YMDD) motif mutation, and the cation of hepatitis B virus in vitro by 2′,3′-dideoxy-3′-thiacyti- incidence of exacerbation is much higher in patients with dine and related analogues. Proc Natl Acad Sci USA 1991; 10 this mutation. As a result it is not recommended that this 88: 8495–8499. drug be administered for long periods of time. We therefore 4 Lai CL, Chien RN, Leung NWY et al. A one-year trial of stopped lamivudine 3 months after transplantation and then lamivudine for chronic hepatitis B. New Engl J Med 1998; carefully followed the serum viral DNA levels. The patient 339: 61–68. experienced viral DNA elevation 4 months later, but was 5 Dienstag JL, Schiff ER, Wright TL et al. Lamivudine as initial again successfully treated with readministration of lamivu- treatment for chronic hepatitis B in the United States. New dine, indicating the virus was still sensitive to this drug. Engl J Med 1999; 341: 1256–1263. Thus, it would appear that lamivudine should be adminis- 6 Gondo H, Harada M, Miyamoto T et al. Autologous peripheral blood stem cell transplantation for acute myelogenous leuke- tered for as short a time as possible, and the HBV DNA mia. Bone Marrow Transplant 1997; 20: 821–826. level carefully monitored, so that the drug can be readmin- 7 Urdea MS, Horn T, Fultz TJ et al. Branched DNA amplifi- istered without delay if necessary. cation multimers for the sensitive, direct detection of human These results suggest that lamivudine may be useful in hepatitis viruses. Nucleic Acids Symp Ser 1991; 24: 197–200. the prophylaxis of HBV fulminant hepatitis following mye- 8 Picardi M, Selleri C, De Rosa G et al. Lamivudine treatment Bone Marrow Transplantation Lamivudine therapy for HBV carrier in PBSC transplant N Uchida et al 1245 for chronic replicative hepatitis B virus infection after allo- 10 Liaw YF, Chien RN, Yeh CT et al. Acute exacerbation and geneic bone marrow transplantation. Bone Marrow Transplant hepatitis B virus clearance after emergence of YMDD motif 1998; 21: 1267–1269. mutation during lamivudine therapy. Hepatology 1999; 30: 9 Clark FL, Drummond MW, Chambers S et al. Successful 567–572. treatment with lamivudine for fulminant reactivated hepatitis B infection following intensive therapy for high-grade non- Hodgkin’s lymphoma. Ann Oncol 1998; 9: 385–387. Bone Marrow Transplantation.
Load more

Recommended publications
  • Design and Evaluation of 5•²-O-Dicarboxylic And
    University of Rhode Island DigitalCommons@URI Open Access Master's Theses 2014 DESIGN AND EVALUATION OF 5′-O-DICARBOXYLIC AND POLYARGININE FATTY ACYL DERIVATIVES OF ANTI-HIV NUCLEOSIDES Bhanu Priya Pemmaraju Venkata University of Rhode Island, [email protected] Follow this and additional works at: https://digitalcommons.uri.edu/theses Recommended Citation Pemmaraju Venkata, Bhanu Priya, "DESIGN AND EVALUATION OF 5′-O-DICARBOXYLIC AND POLYARGININE FATTY ACYL DERIVATIVES OF ANTI-HIV NUCLEOSIDES" (2014). Open Access Master's Theses. Paper 474. https://digitalcommons.uri.edu/theses/474 This Thesis is brought to you for free and open access by DigitalCommons@URI. It has been accepted for inclusion in Open Access Master's Theses by an authorized administrator of DigitalCommons@URI. For more information, please contact [email protected]. DESIGN AND EVALUATION OF 5′-O- DICARBOXYLIC AND POLYARGININE FATTY ACYL DERIVATIVES OF ANTI-HIV NUCLEOSIDES BY BHANU PRIYA, PEMMARAJU VENKATA A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE MASTER’S DEGREE IN BIOMEDICAL AND PHARMACEUTICAL SCIENCES UNIVERSITY OF RHODE ISLAND 2014 MASTER OF SCIENCE THESIS OF BHANU PRIYA, PEMMARAJU VENKATA APPROVED: Thesis Committee: Major Professor Keykavous Parang Roberta King Stephen Kogut Geoffrey D. Bothun Nasser H. Zawia DEAN OF THE GRADUATE SCHOOL UNIVERSITY OF RHODE ISLAND 2014 ABSTRACT 2′,3′-Dideoxynucleoside (ddNs) analogs are the most widely used anti-HIV drugs in the market. Even though these drugs display very potent activities, they have a number of limitations when are used as therapeutic agents. The primary problem associated with ddNs is significant toxicity, such as neuropathy and bone marrow suppression.
    [Show full text]
  • Recent Advances in Antiviral Therapy J Clin Pathol: First Published As 10.1136/Jcp.52.2.89 on 1 February 1999
    J Clin Pathol 1999;52:89–94 89 Recent advances in antiviral therapy J Clin Pathol: first published as 10.1136/jcp.52.2.89 on 1 February 1999. Downloaded from Derek Kinchington Abstract indicated that using a combination of drugs In the early 1980s many institutions in might overcome this problem. The only Britain were seriously considering available drugs during the late 1980s were two whether there was a need for specialist other nucleotide reverse transcriptase inhibi- departments of virology. The arrival of tors (NRTI) which also targeted HIV reverse HIV changed that perception and since transcriptase (HIV-RT): 2',3'-dideoxycytidine then virology and antiviral chemotherapy (ddC) and 2',3'-dideoxyinosine (ddI).56 In have become two very active areas of bio- vitro combination studies gave surprising medical research. Cloning and sequencing results: those viruses that became highly resist- have provided tools to identify viral en- ant to ZDV remained sensitive to both ddC zymes and have brought the day of the and ddI.7 Furthermore, neither cross resistance “designer drug” nearer to reality. At the nor interference between the drugs was an other end of the spectrum of drug discov- issue, and subsequent clinical experience ery, huge numbers of compounds for showed that patients benefited when these two screening can now be generated by combi- compounds were used in combination with natorial chemistry. The impetus to find ZDV.8 It was also found by in vitro studies that drugs eVective against HIV has also virus isolated from patients on long term ZDV stimulated research into novel treatments monotherapy had become insensitive to ZDV, for other virus infections including her- but regained sensitivity when these patients pesvirus, respiratory infections, and were switched to ddI monotherapy.
    [Show full text]
  • Guidelines for the Use of Antiretroviral Agents in Adults and Adolescent Living With
    Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV Developed by the DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents – A Working Group of the Office of AIDS Research Advisory Council (OARAC) How to Cite the Adult and Adolescent Guidelines: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Available at https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/ AdultandAdolescentGL.pdf. Accessed [insert date] [insert page number, table number, etc. if applicable] It is emphasized that concepts relevant to HIV management evolve rapidly. The Panel has a mechanism to update recommendations on a regular basis, and the most recent information is available on the HIVinfo Web site (http://hivinfo.nih.gov). What’s New in the Guidelines? August 16, 2021 Hepatitis C Virus/HIV Coinfection • Table 18 of this section has been updated to include recommendations regarding concomitant use of fostemsavir or long acting cabotegravir plus rilpivirine with different hepatitis C treatment regimens. June 3, 2021 What to Start • Since the release of the last guidelines, updated data from the Botswana Tsepamo study have shown that the prevalence of neural tube defects (NTD) associated with dolutegravir (DTG) use during conception is much lower than previously reported. Based on these new data, the Panel now recommends that a DTG-based regimen can be prescribed for most people with HIV who are of childbearing potential. Before initiating a DTG-based regimen, clinicians should discuss the risks and benefits of using DTG with persons of childbearing potential, to allow them to make an informed decision.
    [Show full text]
  • Safety and Efficacy of Antiviral Therapy for Prevention of Cytomegalovirus Reactivation in Immunocompetent Critically Ill Patien
    1 2 3 PROJECT TITLE 4 Anti-viral Prophylaxis for Prevention of Cytomegalovirus (CMV) Reactivation in Immunocompetent 5 Patients in Critical Care 6 7 STUDY ACRONYM 8 Cytomegalovirus Control in Critical Care - CCCC 9 10 APPLICANTS 11 Dr Nicholas Cowley 12 Specialty Registrar Anaesthesia and Intensive Care Medicine, Intensive Care Research Fellow 13 Queen Elizabeth Hospital Birmingham 14 15 Professor Paul Moss 16 Professor of Haematology 17 Queen Elizabeth Hospital Birmingham 18 19 Professor Julian Bion 20 Professor of Intensive Care Medicine 21 Queen Elizabeth Hospital Birmingham 22 23 Trial Virologist Trial Statistician 24 Dr H Osman Dr P G Nightingale 25 Queen Elizabeth Hospital Birmingham University of Birmingham CCCC CMV Protocol V1.7, 18th September 2013 1 Downloaded From: https://jamanetwork.com/ on 09/23/2021 26 CONTENTS 27 Substantial Amendment Sept 18th 2013 4 28 1 SUMMARY OF TRIAL DESIGN .......................................................................................................... 5 29 2 QEHB ICU Duration of Patient Stay ................................................................................................. 6 30 3 SCHEMA - QEHB PATIENT NUMBERS AVAILABLE FOR RECRUITMENT ........................................... 6 31 4 INTRODUCTION ............................................................................................................................... 7 32 4.1 CMV latent infection is widespread ........................................................................................ 7 33 4.2 CMV Reactivation
    [Show full text]
  • Rational Design and Synthesis of New Nucleoside Analogues Bearing a Cyclohexane Core
    Rational Design and Synthesis of New Nucleoside Analogues Bearing a Cyclohexane Core Beatriz Domínguez Pérez Ph.D. Thesis Ph.D. in Chemistry Supervisors: Dr. Ramon Alibés Arqués Dr. Félix Busqué Sánchez Dr. Jean-Didier Márechal Departament de Química Facultat de Ciències 2015 Memòria presentada per aspirar al Grau de Doctor per Beatriz Domínguez Pérez Beatriz Domínguez Pérez Vist i plau, Dr. Ramon Alibés Arqués Dr. Félix Busqué Sánchez Dr. Jean-Didier Maréchal Bellaterra, 13 de maig de 2015 “When you make the finding yourself-even if you’re the last person on Earth to see the light- you’ll never forget it” Carl Sagan A mis padres, a mi hermana A Jonatan Table of contents Abbreviations................................................................................................................................ 1 I. General introduction ............................................................................................. 5 1. Viruses ................................................................................................................................. 7 1.1. Virus replication ............................................................................................................. 8 1.2. Viral diseases in humans ................................................................................................ 9 2. Antiviral drugs ................................................................................................................... 10 2.1. Nucleoside analogues .................................................................................................
    [Show full text]
  • 1. Global HIV Infection Drug Market Overview 1.1 Global HIV Incidence Scenario 1.2 Market Overview: Global & Regional 1.3 Clinical Pipeline Overview
    August’2014 Global HIV Infection Drug Market & Pipeline Insight Global HIV Infection Drug Market & Pipeline Insight ©KuicK Research Global HIV Infection Drug Market & Pipeline Insight ©KuicK Research All rights reserved. No part of this research study may be reproduced, used, quoted and modified in any form and means without the prior consent of KuicK Research. The use of this research study is only allowed as per the license agreement/purchased from KuicK Research. Global HIV Infection Drug Market & Pipeline Insight ©KuicK Research Page 2 Table of Contents 1. Global HIV Infection Drug Market Overview 1.1 Global HIV Incidence Scenario 1.2 Market Overview: Global & Regional 1.3 Clinical Pipeline Overview 2. Global HIV Infection Drug Market Dynamics 2.1 Favorable Market Drivers 2.2 Market Challenges to be Resolved 2.3 Future Opportunity Outlook 3. FDA Regulatory Framework for Development of HIV Vaccine 3.1 Development of Preventive HIV Vaccines for Use in Paediatric Populations 3.2 Guidance for Submitting HIV Resistance Data 3.3 HIV Resistance Testing in Antiretroviral Drug Development 3.4 HIV-1 Infection: Developing Antiretroviral Drugs for Treatment 4. EMA Regulatory Framework for Development of Medicinal Products for Treatment of HIV Infection 5. Global HIV Infection Drug Clinical Pipeline by Phase, Company & Country 5.1 Phase Unknown 5.2 Research 5.3 Preclinical 5.4 Clinical 5.5 Phase-0 5.6 Phase-I 5.7 Phase-I/II 5.8 Phase-II 5.9 Phase-III 5.10 Preregistration 5.11 Registered Global HIV Infection Drug Market & Pipeline Insight ©KuicK Research Page 3 6.
    [Show full text]
  • Review Nucleoside Analogue-Sparing Strategy for the Treatment of Chronic HIV Infection: Potential Interest and Clinical Experience Véronique Joly* and Patrick Yeni
    Antiviral Therapy 10:29–40 Review Nucleoside analogue-sparing strategy for the treatment of chronic HIV infection: potential interest and clinical experience Véronique Joly* and Patrick Yeni Maladies Infectieuses, Hôpital Bichat Claude Bernard, Paris, France *Corresponding author: Tel: +33 1 4025 7807; Fax: +33 1 4025 6775; E-mail: [email protected] Nucleoside analogue-sparing antiretroviral combinations therapeutic drug monitoring service to confirm that appro- may be interesting as first-line therapies as they spare a priate drug exposures are achieved is useful when using complete class of drugs that will remain fully active for such regimens. Some negative kinetic interactions may lead later use and prevent the risk of mitochondrial toxicity to complicated combinations with a high pill burden that related to exposure to nucleoside reverse transcriptase reduces their applicability. Gastrointestinal toxicity often inhibitors (NRTIs). This strategy is also used in patients remains a limiting factor in the use of boosted double-PI failing NRTIs with cross-resistance to compounds in this combinations. Non-comparative studies have allowed class. Different combinations of antiretroviral drugs are selection of NRTI-sparing options that now need to be theoretically available. Non-nucleoside reverse transcrip- compared with the current standard of care in comparative tase inhibitors (NNRTIs) associated with protease inhibitor clinical trials before being considered as valuable options. (PI) and boosted double-PI combinations have been Other NRTI-sparing therapeutic strategies are emerging: studied through small, non-comparative clinical studies PI monotherapy with lopinavir/ritonavir has been evalu- and preliminary results suggest that they are efficient and ated in a small group of naive patients and appears often well-tolerated.
    [Show full text]
  • Current Drugs to Treat Infections with Herpes Simplex Viruses-1 and -2
    viruses Review Current Drugs to Treat Infections with Herpes Simplex Viruses-1 and -2 Lauren A. Sadowski 1,†, Rista Upadhyay 1,2,†, Zachary W. Greeley 1,‡ and Barry J. Margulies 1,3,* 1 Towson University Herpes Virus Lab, Department of Biological Sciences, Towson University, Towson, MD 21252, USA; [email protected] (L.A.S.); [email protected] (R.U.); [email protected] (Z.W.G.) 2 Towson University Department of Chemistry, Towson, MD 21252, USA 3 Molecular Biology, Biochemistry, and Bioinformatics Program, Towson University, Towson, MD 21252, USA * Correspondence: [email protected] † Authors contributed equally to this manuscript. ‡ Current address: Becton-Dickinson, Sparks, MD 21152, USA. Abstract: Herpes simplex viruses-1 and -2 (HSV-1 and -2) are two of the three human alphaher- pesviruses that cause infections worldwide. Since both viruses can be acquired in the absence of visible signs and symptoms, yet still result in lifelong infection, it is imperative that we provide interventions to keep them at bay, especially in immunocompromised patients. While numerous experimental vaccines are under consideration, current intervention consists solely of antiviral chemotherapeutic agents. This review explores all of the clinically approved drugs used to prevent the worst sequelae of recurrent outbreaks by these viruses. Keywords: acyclovir; ganciclovir; cidofovir; vidarabine; foscarnet; amenamevir; docosanol; nelfi- navir; HSV-1; HSV-2 Citation: Sadowski, L.A.; Upadhyay, R.; Greeley, Z.W.; Margulies, B.J. Current Drugs to Treat Infections 1. Introduction with Herpes Simplex Viruses-1 and -2. The world of anti-herpes simplex (anti-HSV) agents took flight in 1962 with the FDA Viruses 2021, 13, 1228.
    [Show full text]
  • Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2018
    REPORT 2019 Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2018 RAVN Resistensovervåking av virus i Norge Resistance against Antivirals in Norway Usage of Antivirals and the Occurrence of Antiviral resistance in Norway 2018 RAVN Resistensovervåkning av virus i Norge Resistance against antivirals in Norway 2 Published by the Norwegian Institute of Public Health Division of Infection Control and Environmental Health Department for Infectious Disease registries October 2019 Title: Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2018. RAVN Ordering: The report can be downloaded as a pdf at www.fhi.no Graphic design cover: Fete Typer ISBN nr: 978-82-8406-032-3 Emneord (MeSH): Antiviral resistance Any usage of data from this report should include a specific reference to RAVN. Suggested citation: RAVN. Usage of Antivirals and the Occurrence of Antiviral Resistance in Norway 2018. Norwegian Institute of Public Health, Oslo 2019 Resistance against antivirals in Norway • Norwegian Institute of Public Health 3 Table of contents Introduction _________________________________________________________________________ 4 Contributors and participants __________________________________________________________ 5 Sammendrag ________________________________________________________________________ 6 Summary ___________________________________________________________________________ 8 1 Antivirals and development of drug resistance ______________________________________ 10 2 The usage of antivirals in Norway
    [Show full text]
  • Hydroxyurea with Ddi Or Ddi/D4t: a Novel Approach to HIV Therapy
    National AIDS Treatment Advocacy Project Hydroxyurea with ddI or ddI/d4T: a novel approach to HIV therapy Results from several hydroxyurea (ddI+hydroxyurea) studies were reported at Vancouver (July `96) and ICAAC (September, `96). Our Vancouver and ICAAC Conference daily highlights (see Conference Reports) contain data and comments about these studies. Hydroxyurea used alone has not been effective against HIV; up until now findings from studies have shown that the combination of hydroxyurea+ddI can lower viral load in blood and in lymph tissue. The combination of AZT+hydroxyurea is not effectual. The accumulation of data so far has come from small pilot studies sponsored mostly by Bristol-Myers Squibb, although the ACTG started a trial in the Summer of `96. Hydroxyurea has been used as a treatment for several types of cancer for many years, but at significantly higher doses than is being used in its application to HIV disease. How does hydroxyurea work in HIV? Nucleoside analogues such as AZT, d4T, ddI, ddC, 1592U89 and 3TC work by replacing the building blocks for DNA and thereby inhibit the process by which an HIV infected cell reproduces new virus. Hydroxyurea inhibits the building blocks of DNA from being synthesized, thus increasing the opportunity for nucleoside analogues to replace the building blocks and inhibit replication of virus. It appears as though hydroxyurea will be more effective in combination with ddI or ddI/d4T than AZT or ddC. The study discussed below explores its use in combination with ddI/d4T. The use of hydroxyurea in combination with a nucleoside(s) presents a novel concept to HIV therapy.
    [Show full text]
  • Antiviral Research and Development Against Dengue Virus
    Antiviral Research and Development Against Dengue Virus Bruno Canard, PhD. [email protected] 1 Table of Contents Part 1. Antivirals 3 A short historical view on antiviral research and therapies 3 Lessons learned from recent viral diseases and pandemies 3 The methods used to discover antivirals 4 Infected cell assays 5 Knowledge-based methods 5 The source of anti-infectious molecules 6 Why has natural product screening been neglected in antiviral research ? 8 Challenges associated with natural products in antiviral research 8 What is a validated antiviral target ? 9 Animal models 9 Patient cohorts and clinical trials 10 Frequent arguments about antiviral therapy feasibility 10 The introduction of dengue as a druggable disease 11 Diagnostics, and what does it tells us for antiviral therapy ? 11 Current treatment 11 Part 2. Dengue 13 Preamble 13 The Dengue Virus 13 The DENV targets for antiviral research 13 Overview of genome organisation 14 Overview of the DV particle and DV proteins as targets for drugs 14 The structural proteins 14 The Non-Structural proteins 15 RNA structures 17 The dengue validated targets 17 The cellular targets for antiviral research against dengue 18 siRNAs as tools and/or therapeutic agents 19 Response modifiers 20 Monoclonal antibodies 21 Mechanical devices 21 Part 3. Academic and academy-associated research centers 22 Part 4. The current industrial network of AV discovery 31 Part 5. Mapping the dengue drug design effort and needs 38 Annex 1. References 42 Annex 2. Patents 43 2 Part 1. Antivirals A short historical view on antiviral research and therapies The first significant successes of anti-infectious disease treatments originated from the discovery and use of antibiotics.
    [Show full text]
  • Structural Aspects of Drug Resistance and Inhibition of HIV-1 Reverse Transcriptase
    Viruses 2010, 2, 606-638; doi:10.3390/v2020606 OPEN ACCESS viruses ISSN 1999-4915 www.mdpi.com/journal/viruses Review Structural Aspects of Drug Resistance and Inhibition of HIV-1 Reverse Transcriptase Kamalendra Singh, Bruno Marchand, Karen A. Kirby, Eleftherios Michailidis and Stefan G. Sarafianos * Christopher Bond Life Sciences Center & Department of Molecular Microbiology & Immunology, University of Missouri, Columbia, Missouri 65211, USA; E-Mails: [email protected] (K.S.); [email protected] (B.M.); [email protected] (K.A.K.); [email protected] (E.M.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-573-882-4338. Received: 2 December 2009; in revised form: 22 January 2010 / Accepted: 3 February 2010 / Published: 11 February 2010 Abstract: HIV-1 Reverse Transcriptase (HIV-1 RT) has been the target of numerous approved anti-AIDS drugs that are key components of Highly Active Anti-Retroviral Therapies (HAART). It remains the target of extensive structural studies that continue unabated for almost twenty years. The crystal structures of wild-type or drug-resistant mutant HIV RTs in the unliganded form or in complex with substrates and/or drugs have offered valuable glimpses into the enzyme’s folding and its interactions with DNA and dNTP substrates, as well as with nucleos(t)ide reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTIs) drugs. These studies have been used to interpret a large body of biochemical results and have paved the way for innovative biochemical experiments designed to elucidate the mechanisms of catalysis and drug inhibition of polymerase and RNase H functions of RT.
    [Show full text]