DOCSLIB.ORG

HIV/AIDS Presented by America’S Biopharmaceutical Research Companies

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
HIV/AIDS Presented by America’S Biopharmaceutical Research Companies 2012 REPO Medicines in Development HIV/AIDS R PRESENTED BY AMERICA’S BIOPHARMACEUTICAL T RESEARCH COMPANIES Biopharmaceutical Researchers Are Testing More Than 70 Medicines and Vaccines For HIV Infection Medicines in Development for HIV/AIDS 40 1.2 million Americans 25 are living with HIV, 50,000 are newly diagnosed each year 4 4 s Biopharmaceutical research companies vaccine given to only a third of the population are developing 73 medicines and vaccines, could reduce new HIV infections by 24 percent Antivirals Therapy Vaccines focusing on improved treatment regimens, over 15 years. more effective therapies and promising new The medicines in the development pipeline preventative vaccines. Cell/Gene Immunomodulator include: Although HIV/AIDS is one of the most • A gene therapy that uses genetic material to Medicines in Development devastating diseases affecting people around remove disease-causing aspects of the virus. for HIV/AIDS by Phase of the world, the number of new infections has Development been steadily declining. In the United States, • A transdermal vaccine that helps suppress vi- rus replication and destroys HIV-infected cells. 35 the AIDS-related death rate has fallen by 79 percent due to antiretroviral therapy. 28 • A first-in-class medicine intended to prevent the Over the past 30 years, nearly 40 medicines HIV virus from breaking through the cell membrane. have been approved to treat HIV/AIDS. Despite the incredible progress to date, the Testing for the disease also has advanced HIV/AIDS epidemic remains a complex prob- dramatically, enabling earlier treatment. While lem. America’s biopharmaceutical research 5 4 2 these medicines have helped to prolong the companies are continuing their efforts to de- lives of HIV-infected patients, making HIV a velop novel and more effective therapies, vac- manageable chronic disease, opportunities for cines to prevent the disease, and potentially a even greater progress remain. Phase I cure, so the millions of patients suffering today Phase IIPhase III For example, biopharmaceutical companies have hope for a better tomorrow. UnspecifiedApplicationSubmitted are intensifying their efforts to develop vac- * Some medicines are listed in more than one cines that would help prevent HIV. Current phase of development. estimates show that a 50 percent effective Medicines in Development for HIV/AIDS ANTIVIRALS Product Name Sponsor Indication Development Status* abacavir/dolutegravir/lamivudine ViiV Healthcare HIV infection therapy in Phase III fixed-dose combination Rsch. Triangle Park, NC treatment-naive patients (877) 844-8872 (integrase inhibitor/reverse transcriptase inhibitor) amdoxovir (DAPD) RFS Pharma HIV-1 infection treatment Phase II Tucker, GA (404) 601-1430 BI-224436 Gilead Sciences HIV infection treatment Phase I completed (integrase inhibitor) Foster City, CA (800) 445-3235 CB1922 Canopus BioPharma HIV infection treatment Phase II (synthetic steroidal lactone) Studio City, CA www.canopusbiopharma.com cenicriviroc Tobira Therapeutics HIV-1 infection treatment Phase II (CCR5 receptor antagonist) South San Francisco, CA (650) 741-6625 CMX157 Merck HIV infection treatment Phase I completed (tenofovir PIM conjugate) Whitehouse Station, NJ (800) 672-6372 cobicistat Gilead Sciences HIV infection treatment application submitted (PK enhancer) Foster City, CA (800) 445-3235 cobicistat/darunavir Gilead Sciences HIV infection Phase I fixed-dose combination Foster City, CA (800) 445-3235 (PK enhancer/protease Janssen Therapeutics (800) 526-7736 inhibitor) Titusville, NJ cobicistat/darunavir/ Gilead Sciences HIV-1 infection Phase II emtricitabine/GS-7340 Foster City, CA (800) 445-3235 fixed-dose combination Janssen Therapeutics (800) 526-7736 Titusville, NJ cobicistat/elvitegravir/ Gilead Sciences HIV-1 infection Phase II emtricitabine/GS-7340 Foster City, CA (800) 445-3235 fixed-dose combination dapivirine International Partnership for HIV infection prevention Phase I/II completed (NNRTI) Microbicides (vaginal ring) (301) 608-2221 Silver Spring, MD -------------------------------------------------- ------------------------------------------- HIV infection prevention Phase I/II completed (vaginal gel) (301) 608-2221 dolutegravir Shionogi HIV-1 infection treatment Phase III (S/GSK1349572) Florham Park, NJ (973) 966-6900 (integrase inhibitor) ViiV Healthcare (877) 844-8872 Rsch. Triangle Park, NC *For more information about a specific medicine in this report, please call the telephone number listed. 2 Medicines in Development HIV/AIDS 2012 Medicines in Development for HIV/AIDS ANTIVIRALS Product Name Sponsor Indication Development Status efavirenz/lamivudine/ Mylan Laboratories HIV-1 infection treatment application submitted tenofovir fumarate Canonsburg, PA (724) 514-1800 fixed-dose combination elvitegravir Gilead Sciences HIV-1 infection treatment application submitted (integrase inhibitor) Foster City, CA (800) 445-3235 elvucitabine Achillion Pharmaceuticals HIV infection treatment Phase II (NRTI) New Haven, CT (203) 624-7000 GS-7340 Gilead Sciences HIV infection treatment Phase II (NtRTI) Foster City, CA (800) 445-3235 HIV attachment inhibitor Bristol-Myers Squibb HIV infection treatment Phase II Princeton, NJ (800) 332-2056 HIV maturation inhibitor Bristol-Myers Squibb HIV infection treatment in clinical trials Princeton, NJ (800) 332-2056 ibalizumab TaiMed Biologics USA HIV-1 infection treatment Phase II (TMB-355) Irvine, CA (intravenous) (Fast Track) (949) 769-6543 (fusion inhibitor) -------------------------------------------------- ------------------------------------------- HIV-1 infection treatment Phase I (subcutaneous) (949) 769-6543 Intelence® Janssen Therapeutics HIV infection combination therapy in Phase II etravirine Titusville, NJ treatment-naive patients (800) 526-7736 (NNRTI) (Fast Track) KD-247 Kaketsuken HIV-1 infection treatment Phase I (monoclonal antibody) Kumamoto, Japan www.kaketsuken.or.jp KP-1461 Koronis Pharmaceuticals HIV infection treatment Phase II (replication inhibitor) Redmond, WA (425) 825-0240 lamivudine (3TC)/lopinavir/ Abbott Laboratories HIV-1 infection treatment in clinical trials ritonavir fixed-dose Abbott Park, IL (847) 937-6100 combination lamivudine (3TC)/maraviroc/ GlaxoSmithKline HIV infection Phase I completed zidovudine fixed-dose Rsch. Triangle Park, NC (888) 825-5249 combination lersivirine (UK-453061) ViiV Healthcare HIV infection treatment Phase II (NNRTI) Rsch. Triangle Park, NC (877) 844-8872 Lexiva® Vertex Pharmaceuticals HIV infection treatment in Phase II fosamprenavir Cambridge, MA adolescents, children and infants (617) 444-6100 (PI) ViiV Healthcare (877) 844-8872 Rsch. Triangle Park, NC Medicines in Development HIV/AIDS 2012 3 Medicines in Development for HIV/AIDS ANTIVIRALS Product Name Sponsor Indication Development Status MK-1439 Merck HIV-1 infection treatment Phase I (NNRTI) Whitehouse Station, NJ (800) 672-6273 Norvir® Abbott Laboratories HIV infection treatment in clinical trials ritonavir Abbott Park, IL (847) 937-6100 powdered formulation (PI) NRT inhibitor Bristol-Myers Squibb HIV infection treatment Phase II Princeton, NJ (800) 332-2056 Prezista® Janssen Therapeutics HIV infection application submitted darunavir Titusville, NJ (800) 526-7736 (once-daily 800 mg) PRO 140 CytoDyn HIV-1 infection prevention and Phase II completed (CCR5 receptor antagonist) Lake Oswego, OR treatment (971) 204-0382 RAP101 RAPID Pharmaceuticals HIV infection treatment Phase II (CCR5 receptor antagonist) Huenenberg, Switzerland www.rapidpharma.com RPI-MN ReceptoPharm HIV infection treatment Phase I Plantation, FL (954) 321-8988 S/GSK1265744 Shionogi HIV infection treatment Phase II (integrase inhibitor) Florham Park, NJ (973) 966-6900 ViiV Healthcare (877) 844-8872 Rsch. Triangle Park, NC SPL-7013 Starpharma HIV infection prevention Phase I completed (vaginal gel) Melbourne, Australia (Fast Track) www.starpharma.com TBR-220 Tobira Therapeutics HIV infection treatment Phase I (CCR5 receptor antagonist) South San Francisco, CA (650) 741-6625 tenofovir vaginal gel CONRAD HIV infection prevention Phase I (NtRTI) Arlington, VA (703) 524-4744 International Partnership for Microbicides Silver Spring, MD TMC310911 Janssen Therapeutics HIV infection treatment Phase II completed (PI) Titusville, NJ (800) 526-7736 4 Medicines in Development HIV/AIDS 2012 Medicines in Development for HIV/AIDS ANTIVIRALS Product Name Sponsor Indication Development Status UB-421 United Biomedical HIV-1 infection treatment Phase II (FI) Hauppauge, NY (631) 273-2828 VRX806 Valeant Pharmaceuticals HIV infection treatment Phase II (NNRTI) Mississauga, Canada (905) 286-3000 CELL THERAPY/GENE THERAPY Product Name Sponsor Indication Development Status HIV gene therapy Adaptimmune HIV infection Phase I Philadelphia, PA (267) 499-2066 Cardiff University Cardiff, Wales University of Pennsylvania Philadelphia, PA lexgenleucel-T VIRxSYS HIV infection therapy in Phase II (replication inhibitor) Gaithersburg, MD treatment-experienced patients (301) 987-0480 SB-728-T Sangamo BioSciences HIV infection treatment Phase II Richmond, CA (510) 970-6000 Stealth Vector® Enzo Therapeutics HIV-1 infection treatment Phase I/II HGTV-43™ New York, NY (212) 583-0100 antisense gene medicine IMMUNOMODULATORS Product Name Sponsor Indication Development Status AMZ0026 Amazon Biotech HIV infection treatment Phase I/II New York, NY (212) 444-1019 CYT107 Cytheris HIV infection treatment Phase II (recombinant human Rockville, MD (301) 231-0450 interleukin-7) Cytolin® CytoDyn HIV infection treatment
Load more

Recommended publications
  • Download Article PDF/Slides
    Kan Lu, PharmD New Antiretrovirals for Based on a presentation at prn by Roy M. Gulick, md, mph the Treatment of HIV: Kan Lu, PharmD | Drug Development Fellow University of North Carolina School of Pharmacy Chapel Hill, North Carolina The View in 2006 Roy M. Gulick, md, mph Reprinted from The prn Notebook® | october 2006 | Dr. James F. Braun, Editor-in-Chief Director, Cornell Clinical Trials Unit | Associate Professor of Medicine, Meri D. Pozo, PhD, Managing Editor. Published in New York City by the Physicians’ Research Network, Inc.® Weill Medical College of Cornell University | New York, New York John Graham Brown, Executive Director. For further information and other articles available online, visit http://www.prn.org | All rights reserved. ©october 2006 substantial progress continues to be made in the arena of cokinetics and a long extracellular half-life of approximately 10 hours antiretroviral drug development. prn is again proud to present its annual (Zhu, 2003). During apricitabine’s development, a serious drug interac- review of the experimental agents to watch for in the coming months and tion with lamivudine (Epivir) was noted. Although the plasma years. This year’s review is based on a lecture by Dr. Roy M. Gulick, a long- concentrations of apricitabine were unaffected by coadministration of time friend of prn, and no stranger to the antiretroviral development lamivudine, the intracellular concentrations of apricitabine were reduced pipeline. by approximately sixfold. Additionally, the 50% inhibitory concentration To date, twenty-two antiretrovirals have been approved by the Food (ic50) of apricitabine against hiv with the M184V mutation was increased and Drug Administration (fda) for the treatment of hiv infection.
    [Show full text]
  • Download Article PDF/Slides
    New Antiretrovirals in Development: Reprinted from The PRN Notebook,™ june 2002. Dr. James F. Braun, Editor-in-Chief. Tim Horn, Executive Editor. Published in New York City by the Physicians’ Research Network, Inc.,® John Graham Brown, Executive Director. For further information and other articles The View in 2002 available online, visit http://www.PRN.org All rights reserved. © june 2002. Roy “Trip” Gulick, md, mph Associate Professor of Medicine, Weill Medical College of Cornell University Director, Cornell Clinical Trials Unit, New York, New York Summary by Tim Horn Edited by Scott Hammer, md espite the fact that 16 antiretro- tiviral activity of emtricitabine was estab- Preliminary results from two random- virals are approved for use in the lished, with total daily doses of 200 mg or ized studies—FTC-302 and FTC-303—were United States, there is an indis- more producing the greatest median viral reported by Dr. Charles van der Horst and putable need for new anti-hiv com- load suppression: 1.72-1.92 log. Based on his colleagues at the 8th croi, held in Feb- pounds that have potent and these data, a once-daily dose of 200 mg ruary 2001 in Chicago (van der Horst, durable efficacy profiles, unique re- was selected for further long-term clinical 2001). FTC-302 was a blinded comparison sistance patterns, patient-friendly dosing study. “This is what we’re looking forward of emtricitabine and lamivudine, both in schedules, and minimal toxicities. To pro- to with emtricitabine,” commented Dr. combination with stavudine (Zerit) and vide prn with a glimpse of drugs current- Gulick.
    [Show full text]
  • 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.
    [Show full text]
  • Ep 2531027 B1
    (19) TZZ ¥_Z _T (11) EP 2 531 027 B1 (12) EUROPEAN PATENT SPECIFICATION (45) Date of publication and mention (51) Int Cl.: of the grant of the patent: A61K 31/4985 (2006.01) A61K 31/52 (2006.01) 06.05.2015 Bulletin 2015/19 A61K 31/536 (2006.01) A61K 31/513 (2006.01) A61K 38/55 (2006.01) A61P 31/18 (2006.01) (21) Application number: 11737484.3 (86) International application number: (22) Date of filing: 24.01.2011 PCT/US2011/022219 (87) International publication number: WO 2011/094150 (04.08.2011 Gazette 2011/31) (54) Therapeutic combination comprising dolutegravir, abacavir and lamivudine Therapeutische Zusammensetzung enthaltend Dolutegravir, Abacavir und Lamivudine Combinaison thérapeutique comprenant du dolutégravir, de l’abacavir et de la lamivudine (84) Designated Contracting States: (74) Representative: Gladwin, Amanda Rachel AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GlaxoSmithKline GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO Global Patents (CN925.1) PL PT RO RS SE SI SK SM TR 980 Great West Road Designated Extension States: Brentford, Middlesex TW8 9GS (GB) BA ME (56) References cited: (30) Priority: 27.01.2010 US 298589 P WO-A1-2010/011812 WO-A2-2009/148600 US-A1- 2006 084 627 US-A1- 2006 084 627 (43) Date of publication of application: US-A1- 2008 076 738 US-A1- 2009 318 421 12.12.2012 Bulletin 2012/50 US-A1- 2009 318 421 US-B1- 6 544 961 (73) Proprietor: VIIV Healthcare Company • SONG1 et al: "The Effect of Ritonavir-Boosted Research Triangle Park, NC 27709 (US) ProteaseInhibitors on the HIV Integrase Inhibitor, S/GSK1349572,in Healthy Subjects", INTERNET , (72) Inventor: UNDERWOOD, Mark, Richard 15 September 2009 (2009-09-15), XP002697436, Research Triangle Park Retrieved from the Internet: URL:http: North Carolina 27709 (US) //www.natap.org/2009/ICCAC/ICCAC_ 52.htm [retrieved on 2013-05-21] Note: Within nine months of the publication of the mention of the grant of the European patent in the European Patent Bulletin, any person may give notice to the European Patent Office of opposition to that patent, in accordance with the Implementing Regulations.
    [Show full text]
  • 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
    [Show full text]
  • The Design, Synthesis and Optimization of Allosteric Hiv-1
    THE DESIGN, SYNTHESIS AND OPTIMIZATION OF ALLOSTERIC HIV-1 INTEGRASE INHIBITORS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Janet Antwi Graduate Program in Pharmaceutical Sciences The Ohio State University 2017 Dissertation Committee: Professor James R. Fuchs, Advisor Professor Werner Tjarks Professor Karl A. Werbovetz Copyright by Janet Antwi 2017 Abstract In the past quarter century, there has been tremendous progress in the discovery of antiretroviral therapy, making HIV/AIDS a manageable chronic disease. However, the HIV virus is relentless and continues to evolve under drug pressure to escape control and continue infection. The enzyme HIV integrase is responsible for the incorporation of viral double stranded DNA into a host chromosomal DNA and has recently become an attractive target in combating HIV resistance. Raltegravir (RAL), elvitegravir (EVG) and dolutegravir (DTG) are three clinically approved active-site integrase inhibitors. Unfortunately, mutations of the enzyme observed in patients have resulted in resistance to thedrug in the clinic. A new approach to targeting integrase (IN) is the development of allosteric inhibitors that specifically target the protein-protein interaction between IN and its cellular cofactor LEDGF/p75. Recently discovered quinoline-based allosteric integrase inhibitor (ALLINI) B1224436 was the first compound to advance into clinical trials but was discontinued due to poor pharmacokinetic properties including low in vivo clearance. In addition, several reports have revealed the emergence of resistance due to mutation to quinoline based ALLINIs. Applying scaffold hopping approach, several pyridine-based, thiophenes, ii pyrazoles, isoquinolines and other heteroaromatic cores have been studied as ALLINIs.
    [Show full text]
  • 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.
    [Show full text]
  • HIV/AIDS Technologies: a Review of Progress to Date and Current Prospects
    Working Paper No.6 HIV/AIDS Technologies: A review of progress to date and current prospects COMMISSIONED BY: aids2031 Science and Technology Working Group AUTHORED BY: KEITH ALCORN NAM Publications Disclaimer: The views expressed in this paper are those of the author(s) and do not necessarily reflect the official policy, position, or opinions of the wider aids2031 initiative or partner organizations aids2031 Science and Technology working group A review of progress to date and current prospects October 2008 Acronyms 3TC lamivudine ANRS Agènce Nationale de Récherche sur la Sida ART Antiretroviral therapy ARV Antiretroviral AZT azidothymidine or zidovudine bDNA branched DNA CDC US Centers for Disease Control CHER Children with HIV Early Antiretroviral therapy (study) CTL Cytotoxic T-lymphocyte D4T stavudine DSMB Data and Safety Monitoring Board EFV Efavirenz ELISA Enzyme Linked Immunosorbent Assay FDC Fixed-dose combination FTC Emtricitabine HAART Highly Active Antiretroviral Therapy HBAC Home-based AIDS care HCV Hepatitis C virus HPTN HIV Prevention Trials Network HSV-2 Herpes simplex virus type 2 IAVI International AIDS Vaccine Initiative IL-2 Interleukin-2 LED Light-emitting diode LPV/r Lopinavir/ritonavir MIRA Methods for Improving Reproductive Health in Africa trial MSF Médecins sans Frontières MSM Men who have sex with men MVA Modified vaccinia Ankara NIH US National Institutes of Health NRTI Nucleoside reverse transcriptase inhibitor NNRTI Non-nucleoside reverse transcriptase inhibitor OBT Optimised background therapy PCR Polymerase
    [Show full text]
  • Original Article Antiviral Activity and Tolerability of Amdoxovir with Zidovudine in a Randomized Double-Blind Placebo- Controlled Study in HIV-1-Infected Individuals
    Antiviral Therapy 2010 15:185–192 (doi: 10.3851/IMP1514) Original article Antiviral activity and tolerability of amdoxovir with zidovudine in a randomized double-blind placebo- controlled study in HIV-1-infected individuals Robert L Murphy1, Nancy M Kivel2, Carlos Zala3, Claudia Ochoa3, Phillip Tharnish2, Judy Mathew 2, Maria Luz Pascual2, Raymond F Schinazi4* 1Northwestern University, Feinberg School of Medicine, Chicago, IL, USA 2RFS Pharma, LLC, Tucker, GA, USA 3Hospital Privado Modelo, Florida-Buenos Aires B1602DBG, Argentina 4Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA, USA *Corresponding author e-mail: [email protected] Background: Amdoxovir acts synergistically with zido- day 10 were determined. Laboratory and clinical safety vudine in vitro and the combination prevents or delays monitoring were performed. the selection of thymidine analogue and K65R muta- Results: Twenty-four patients were enrolled. The mean tions. In silico studies have shown that a reduced dose VL log10 change was 0.10 with placebo, -0.69 with zido- of zidovudine (200 mg) results in decreased zidovudine- vudine 200 mg, -0.55 with zidovudine 300 mg, -1.09 monophosphate levels, associated with toxicity, while with amdoxovir, -2.00 with amdoxovir plus zidovudine maintaining zidovudine-triphosphate levels, which are (200 mg) and -1.69 with amdoxovir plus zidovudine associated with antiviral effects. Here, we aimed to (300 mg). Amdoxovir plus zidovudine (200 mg) was assess the short-term tolerability and antiviral activity significantly more potent than amdoxovir monotherapy of amdoxovir in combination with reduced and standard in AUCVL and mean VL decline (P=0.019 and P=0.021, doses of zidovudine.
    [Show full text]
  • Mutational Studies of Novel Screened Molecules Against Wild and Mutated HIV-1 Integrase Using Molecular Docking Studies Pawan Gupta1,2*, Prabha Garg2
    Research Article Mutational studies of novel screened molecules against wild and mutated HIV-1 integrase using molecular docking studies Pawan Gupta1,2*, Prabha Garg2 ABSTRACT Background and Aim: The screened molecules which proposed novel HIV-1 integrase inhibitors were collected from the literature. Mutational studies were performed to check whether these molecules are having good binding affinity against mutated HIV-1 IN or not using molecular docking technique. Materials and Methods: First, homology models of the mutated HIV-1 IN were prepared and subsequently all the models were refined and optimized in MODELLER program. Next, molecular docking studies were performed into the active site of mutated HIV-1 IN models using the proposed inhibitors in AutoDock 4.1 program. The results of these studies were compared with the wild type docking studies. Results: The docking studies were found that some of the screened molecules (ZINC1245110, 131614, 92749, ZINC05181828, and ZINC13147504) followed the same binding patterns (in term of locations, interactions, and binding score) as found with wild type HIV-1 IN. Conclusions: Computationally, the same binding patterns were exhibited by these molecules (ZINC1245110, 131614, 92749, ZINC05181828, and ZINC13147504) against mutated models as wild type. This elucidated that these molecules having susceptibility against the drug-resistant HIV-1 IN. Hence, these molecules may be used as a starting point to design novel inhibitors against mutated HIV-1 IN, which need to be confirmed experimentally. KEY WORDS: Docking, Drug resistance, Homology modeling, HIV-1 integrase, Mutation INTRODUCTION Drug resistance is the inevitable consequence of incomplete suppression of HIV-1 replication. The Human immuno-virus (HIV) causes AIDS.
    [Show full text]
  • Multi-Class Immune-Based Therap I Es Co Combination Drugs AZ T
    m- IMMUNE-BASED THERAP o /R) c VIR, A LPV ) MULTI-CLASSA NFV VIR, A S T N (INDIN COMBINATION DRUGSA VIR, REZIST AZ R 754) P A ) AVX C + Inhibitors Protease RTV VIR/RITON ) CRIXIV AB A OM (KIVEXA, COMBIVIR (ZIDOVUDINE + LAMIVUDINE, AZT + 3TC) EMTRIVA Protease754, Inhibitors C VIR, (EMTRICITABINE, FTC) EPIVIR (LAMIVUDINE, 3TC) EPZICOM (KIVEXA, TPV T A PZI HE EPT (NELFIN SPD OVIR DISOPROXIL ABACAVIR + LAMIVUDINE, ABC + 3TC) RETROVIR (ZIDOVUDINE, AZT, E HIBITO F VIR, , LOPIN ZDV) TRIZIVIR (ABACAVIR + ZIDOVUDINE + LAMIVUDINE, ABC + AC A A S IR N IN TRUGGLE FOR AZT + 3TC) TRUVADA (TENOFOVIR DF + EMTRICITABINE, TDF + V ENO A ) T ABINE ( ABINE FTC) VIDEX & VIDEX EC (DIDANOSINE, DDI) VIREAD (TENOFOVIR T TV I THE (ALUVI C DISOPROXIL FUMARATE, TDF) ZERIT (STAVUDINE, D4T) ZIAGEN A (ABACAVIR, ABC) RACIVIR (RCV) AMDOXOVIR (AMDX, DAPD) ORVIR (RITON N PRI VIR, A ) IREAD ( A A V APRICITABINE (SPD754, AVX754)ELVUCITABINE (ACH- TORS ) LETR N ) A I 126,443, BETA-L-FD4C) COMBIVIR (ZIDOVUDINE + FPV A Z I LAMIVUDINE, AZT + 3TC) EMTRIVA (EMTRICITABINE, ) K A ) APTIVUS (TIPR DAPD T VIR, IPTASE IPTASE , A FTC) EPIVIR (LAMIVUDINE, 3TC) EPZICOM (KIVEXA, A PV A SQV CCESS TO ABACAVIR + LAMIVUDINE, ABC + 3TC) RETROVIR R Z ( PIVIR (LAMIVUDINE, 3TC) B A This book documents the struggle that has been faced by those E (ZIDOVUDINE, AZT, ZDV) TRIZIVIR (ABACAVIR + T AMDX VIR, VIR, A A A I STRUGGLEA requiring treatment for HIV/AIDS in India, and those affected ZIDOVUDINE + LAMIVUDINE, ABC + AZT + 3TC) MPREN AVIR + ZIDOVUDINE + LAMIVUDINE, SC EY A C TRUVADA (TENOFOVIR DF + EMTRICITABINE, by HIV/AIDS, since the first recorded incidence of HIV/AIDS in FOR R N ) TDF + FTC) VIDEX & VIDEX EC (DIDANOSINE, QUIN India in 1986.
    [Show full text]
  • Fourth Quarter Product Sales of $2.13 Billion, up 11% Year Over Year
    Gilead Sciences Announces Fourth Quarter and Full Year 2011 Financial Results February 2, 2012 4:06 PM ET - Fourth Quarter Product Sales of $2.13 Billion, up 11% Year over Year - - Full Year 2011 Product Sales of $8.10 Billion, up 10% over 2010 - - Full Year 2011 Non-GAAP EPS of $3.86, up 5% over 2010 - - Full Year 2011 Operating Cash Flows of $3.64 Billion - FOSTER CITY, Calif.--(BUSINESS WIRE)--Feb. 2, 2012-- Gilead Sciences, Inc. (Nasdaq:GILD) announced today its results of operations for the fourth quarter and full year 2011. Total revenues for the fourth quarter of 2011 increased 10 percent to $2.20 billion, from $2.00 billion for the fourth quarter of 2010. Net income for the fourth quarter of 2011 was $665.1 million, or $0.87 per diluted share, compared to $629.4 million, or $0.76 per diluted share for the fourth quarter of 2010. Non-GAAP net income for the fourth quarter of 2011, which excludes after-tax acquisition-related, restructuring and stock-based compensation expenses, was $743.1 million, or $0.97 per diluted share, compared to $779.3 million, or $0.95 per diluted share for the fourth quarter of 2010. Full year 2011 total revenues were $8.39 billion, up 5 percent compared to $7.95 billion for 2010. Net income for 2011 was $2.80 billion, or $3.55 per diluted share, compared to $2.90 billion, or $3.32 per diluted share for 2010. Non-GAAP net income for 2011, which excludes after-tax acquisition-related, restructuring and stock-based compensation expenses, was $3.04 billion, or $3.86 per diluted share, compared to $3.21 billion, or $3.69 per diluted share for 2010.
    [Show full text]