DOCSLIB.ORG

Supplementary Table 1. Available Resistance Fold Change Data

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Supplementary Table 1. Available Resistance Fold Change Data Supplementary Table 1. Available resistance fold change data through literature search for the mutations/polymorphisms identified in the present study Target Mutationa Resistance fold change (compared with wild type of specific genotype)b GT 1a GT 1b GT 2a GT 3a GT 4a GT 5a GT 6a NS3 V36I protease V36L 2ASU [1] 1ASU [1] ≤1.3SIM [2] 1.3SIM [2] ≤1.3SIM [2] 2PAR [3] 1.7SIM [4] V36M 2ASU [1] 2ASU [1] 1.4GLE [5] <2DAN [6] 1.9GRA [5] 2SIM [4] 2PAR [3] >2.5VOX [7] 1.5SIM [8] 0.9VOX [8] Q41H T54A 0.4ASU [1] 0.4ASU [1] 0.8GRA [8] 1.3DAN [4] 0.5PAR [8] 1GLE [5] 0.4SIM [8] 1PAR [3] 0.6VOX [8] 0.6SIM [4] T54G T54S 1ASU [1] 1.2SIM [4] ≤1.3SIM [2] 1GLE [5] 1.1GRA [9] 0.4PAR [3] V55A 1ASU [1] 0.4GLE [5] 1PAR [3] V55G V55I 3ASU [1] 0.2GLE [5] 0.7GRA [5] 1PAR [3] V55P Y56F Q80D Q80G 9.8DAN [4] 1.8SIM [4] Q80K 3ASU [1] 6.5ASU [1] >2.5VOX [7] 8SIM [2] 8SIM [2] 0.9GLE [5] 2.3DAN [4] 1.1GRA [9] 7.7SIM [4] 3PAR [3] 11SIM [10] 0.8VOX [8] Q80L 1ASU [1] 1ASU [1] 2PAR [3] 1.9GRA [8] 1PAR [8] 2.1SIM [4] 1.3VOX [8] Q80M Q80N Q80R 2PAR [3] 4ASU [1] 0.4ASU [8] 3.5DAN [4] 0.1GRA [8] 6.9SIM [4] 0.2PAR [8] 0.5SIM [8] 0.8VOX [8] V107I S122G 1ASU [1] 0.5SIM [10] ≤1SIM [2] S122K S122N 1ASU [1] 1ASU [1] ≤1.3SIM [2] S122R 3ASU [1] 21SIM [10] 1.8GRA [9] S122T 1ASU [1] <1SIM [2] ≤1SIM [2] I132L I132V R155K 21ASU [1] 27ASU [1] 1ASU [8] 22ASU [8] 0.5GLE [5] 410DAN [11] 0.5GLE [5] 2.2GRA [8] 3GRA [9] 0.6GLE [5] 0.1GRA [5] 9.3PAR [8] 37PAR [3] 2.2GRA [12] 5.2PAR [5] 113SIM [8] 86SIM [10] 40PAR [3] >2.8SIM [8] 0.6VOX [8] 0.7VOX [8] 30SIM [4] 0.4VOX [8] 1.5VOX [8] R155P A156V NRASU [8] 20ASU [1] 5.4ASU [8] 23GRA[8] 9.9ASU [8] >2.5VOX [7] >2.5VOX [7] NRGRA [8] 63DAN [4] 1143GLE [5] >1334VOX [8] 3106GLE [5] NRPAR [8] 1786GLE [5] 14552b;GLE [5] 602GRA [5] NRSIM [8] 1200GRA [13] 187GRA [5] 155PAR [5] NRVOX [8] 21PAR [5] 4732b;GRA [5] >208SIM [8] 177SIM [4] 2.2PAR [5] >309VOX [8] 458VOX [8] 52b;PAR [5] 26SIM [8] >129VOX [8] >2.52b;VOX [7] V158I V158L V158M A166S A166T D168E 58ASU [1] 78ASU [1] 3.3GLE [5] 9.1ASU [8] 4.2GLE [5] 1.3GLE [5] 29DAN [11] 2.12b;GLE [5] 4.9GRA [8] 9.6GRA [5] 16GRA [12] 0.9GLE [5] 5.9GRA [5] 6.7PAR [8] 23PAR [5] 14PAR [3] 3.2GRA [12] 5.72b;GRA [5] 20SIM [8] 69SIM [8] 4PAR [3] 5.3PAR [5] 2.7VOX [8] 0.7VOX [8] 40SIM [4] 2.22b;PAR [5] 1.2VOX [8] D168Q >700SIM [2] D168T 205ASU [14] 300DAN [11] >2.5VOX [7] >2.5VOX [7] 49PAR [3] 308SIM [4] V170A 2ASU [1] <2DAN [6] 1.1GLE [5] 6.9GRA [8] 1PAR [3] 1.8SIM [4] 4.6VOX [8] V170I* 1ASU [1] 1ASU [1] <1SIM [2] ≤1SIM [2] 1.05DAN [11] M175L* NS5A K24A 38T24A;OMB [15] 1.3T24A;PIB [16] K24F K24G 3.3DAC [17] 43.3LED [17] 1.4VEL [17] K24Q K24R 2.1DAC [17] 1ELB [9] 3.7LED [17] 1.1VEL [17] K24S K24T 0.4ELB [9] M28A 4591DAC [18] 61ELB [19] 1195LED [17] 25.4VEL [17] M28C M28F 472b;L28F;OMB [15] 0.82b;L28F;PIB [16] M28G >22007DAC [17] >10368LED [17] 11940VEL [17] M28I 1.2DAC [20] 79L28I;OMB [15] 0.3LED [17] 1.1L28I;PIB [16] 1.2VEL [17] M28L 2L28M;DAC [21] 57.5L28M;LED [22] 2L28M;ELB [19] 2L28M;OMB [15] M28S 7735F28S;DAC [23] 4710F28S;OMB [15] 1.2F28S;PIB [16] M28T 682DAC [18] 20L28T;DAC [21] 659OMB [15] 15ELB [9] 661L28T;OMB [15] 1.7PIB [16] 61LED [24] 0.9L28T;PIB [16] ≤10ODA [25] 8965OMB [26] 2.1PIB [16] 7.5VEL [27] <10RUZ [28] M28V 1.3DAC [18] 1.3L28V;ELB [29] 66.9L28V;LED [22] 1ELB [9] 23L28V;OMB [15] 0.6LED [24] 1.1L28V;PIB [16] 58OMB [26] 1.8PIB [16] Q30A Q30H 1477DAC [18] ≤10R30H;DAC [30] 155R30H;DAC [31] 6ELB [9] 1215L30H;DAC [31] 183LED [24] 1.3L30H;PIB [16] ≤1ODA [25] 1.5L30H;VEL [27] 3OMB [15] 1PIB [16] <10RUZ [28] 2.3VEL [27] Q30K 24545DAC [18] 0.1K30Q;DAC [23] 62A30K;DAC [32] 1550LED [17] 50A30K;ELB [19] ≤10ODA [25] 50A30K;VEL [27] 10.4VEL [27] Q30L 3.7DAC [33] 4.3LED [17] 0.5VEL [27] Q30M Q30N Q30R 1227DAC [18] 1R30Q;DAC [21] 37L30R;LED [22] 16ELB [9] 0.4R30Q;OMB [15] 2.4L30R;VEL [27] 632LED [24] ≤10ODA [25] 800OMB [26] 1.7PIB [16] <10RUZ [28] 2.2VEL [27] Q30S 167 R30S;DAC [31] 4 L30S;ELB [34] 1.1L30S;VEL [27] Q30T 5DAC [17] 0.4A30T;DAC [32] 4.4LED [17] 1VEL [17] L31I 35.9DAC [17] 3.4DAC [17] >370LED [17] 29.4LED [17] 4.4VEL [27] 9.7VEL [17] L31M 341DAC [18] 3DAC [21] 141DAC [23] 70.8VEL [27] 878DAC [35] 10ELB [9] 1ELB [19] <12b;M31L;ELB [9] 554LED [24] 0.9OMB [15] ≤1ODA [25] ≤1ODA [25] 1.7VEL [27] ≤12b;ODA [25] 2OMB [26] 1.22b;PIB [16] 1.1PIB [16] 1.5VEL [27] <10RUZ [28] 16VEL [27] L31V 3386DAC [18] 23DAC [21] 5112b;OMB [15] 0.3VEL [27] 2.5 M31V;ELB [34] 458DAC [35] 68OMB [15] 61ELB [9] 4ELB [19] 0.52b;PIB [16] 243OMB [15] 1PIB [16] 683LED [17] 42.9LED [17] 10.1VEL [27] 0.8PIB [16] ≤1ODA [25] ≤1ODA [25] >100OMB [28] 8OMB [15] 1.3PIB [16] <10RUZ [28] <10RUZ [28] 2.3VEL [27] 67.5VEL [27] H58A 47T58A;DAC [35] 18T58A;OMB [15] 1.4T58A;PIB [16] H58C H58D 500DAC [18] 31P58D;DAC [17] 6ELB [9] 238P58D;LED [17] 1127LED [24] 1.8P58D;VEL [17] ≤10ODA [25] 243OMB [15] 1.1PIB [16] 7.3VEL [27] H58G H58L H58N 532T58N;DAC [35] 101T58N;OMB [15] 1.8T58N;PIB [16] H58P 1.2DAC [18] 1P58H;DAC [21] 0.5OMB [26] H58Q H58R H58S 1P58S;DAC [21] 48T58S;DAC [35] 18T58S;OMB [15] H58T 1.5P58T;LED [22] H58Y E62A E62D 2DAC [20] E62G E62H E62I E62K E62L 2S62L;DAC [32] E62M E62N E62Q E62R E62S E62T E62V E62Y A92C A92E 0.8DAC [17] 0.3LED [17] 0.7VEL [17] A92G A92P 1ELB [19] A92S A92T 1.3DAC [17] 15.2LED [17] 1.2VEL [17] A92V Y93C 1864DAC [18] 3.5DAC [33] 1.2VEL [27] 11ELB [9] 1.7ELB [29] 1602LED [24] 5.3LED [17] ≤100ODA [25] 0.2VEL [27] 1675OMB [15] 1.7PIB [16] 3.8VEL [27] Y93H 5432DAC [18] 19DAC [21] 749DAC [23] 2752DAC [32] 169DAC [31] 220ELB [9] 17ELB [19] 45.7VEL [27] 485ELB [19] 7.5ELB [34] 1677LED [24] 1807LED [17] >1000LED [28] 135LED [22] ≤1000ODA [25] ≤10ODA [25] 6728OMB [15] 2.9VEL [27] 41383OMB [15] 77OMB [15] 2.3PIB [16] 6.7PIB [16] 0.6PIB [16] 723.5VEL [27] <10RUZ [28] <10RUZ [28] 609.1VEL [27] 3.3VEL [27] Y93I Y93R 497.2VEL [27] 454DAC [31] Y93S 2734DAC [17] 3.4DAC [17] 1626LED [17] 141.6LED [17] 1013OMB [15] 0.6VEL [27] 63.9VEL [27] Y93T V121I* 0.2ELB [19] NS5B A15C A15G 0.84S15G;SOF [36] A15I A15N A15R A15S A15T A15V L159F 1.2SOF [17] 1.3SOF [37] 1.6SOF [37] 1SOF [37] I239L I239V S282C S282R S282T 8.4SOF [17] 0.8BEC [38] 2.4SOF [10] 3.5SOF [37] 6.1SOF[22] 18.1SOF [10] 7.8SOF [10] 8.8SOF [37] 16.22b;SOF [37] C316G C316H >100DAS [39] >100DAS [39] 0.9SOF [37] 0.9SOF [37] C316N 1.6SOF [37] 5DAS [40] 1SOF [37] C316R C316Y 1472DAS [40] 0.4BEC [38] 1569DAS [40] 0.61SOF[36] L320R L320Y V321F V321I 0.84SOF [36] 0.7SOF [22] V321Y S368A S368P N411D N411S 84DAS [40] N411T M414A M414I 8DAS [26] 2-20DAS [39] M414L M414Q M414S M414V 32DAS [40] 47DAS [40, 41] L419I L419V A421M A421S A421T A421V R422K 144.7RAD [42] 814.6RAD [42] M423A M423I 10.6RAD [42] 4.6RAD [42] M423T 15.8RAD [42] 1BEC [38] 0.4DAS [40] 19.3RAD [42] 0.9SOF [36] M423V 8.5RAD [42] 7RAD [42] M426A M426C M426F M426I M426L 1.1RAD [42] M426T M426V C445F 16DAS [40] 1.6SOF [43] C445W C445Y Y448C 940DAS [40] 414DAS [40] C451A C451H C451I C451N C451R C451S 16DAS [40] C451T C451V C451W C451Y I482L 26.1RAD [42] 51.4RAD [42] A486G A486S A486V 39.6RAD [42] 49.8RAD [42] V494A 17.4RAD [42] 18.1RAD [42] 3.4BEC [44] 17BEC [44] V494C V494I 0.6RAD [42] V494M V494S 34C494S;BEC [44] P495L 32BEC [44] 53BEC [44] 1SOF [36] P496S V499A* 1.6BEC [44] 1.4DAS [40] V499I V499M V499T A553G A553P A553S A553T 152DAS [26] A553V 120DAS [40] G554A G554C G554S 198DAS [26] S556A S556C S556D S556G 30DAS [40] 11DAS [40] S556N 29DAS [40] S556R >100DAS [39] D559H D559I D559N D559Q NS3 protease: Fold change 0 to <10 (highlighted in green), Fold change 10 to 30 (highlighted in orange), Fold change >30 (highlighted in red) NS5A: Fold change 0 to <10 (highlighted in green), Fold change 10 to 50 (highlighted in orange), Fold change >50 (highlighted in red) NS5B: Fold change 0 to <10 (highlighted in green), Fold change 10 to 50 (highlighted in orange), Fold change >50 (highlighted in red) a = residue index as per GT 1a; *residue at this position has been swapped (i.e.
Load more

Recommended publications
  • Tuesday 6 June
    Tuesday 6 June 14:00- Registration at the Conference Venue 18:00 19:00- Opening ceremony, welcome reception and dinner 22:00 Wednesday 7 June 08:00- Registration 08:45 08:45- Welcome and Introduction 09:00 09:00- Benefit-risk profile of medicinal Chair: Oscar 10:30 products Della Pasqua Overview and implementation of multi criteria 09:00- Praveen decision analysis (MCDA) for benefit-risk 09:30 Thokala assessment European regulatory views on benefit-risk 09:30- Andreas assessment methodologies - role of MCDA and 10:00 Kouroumalis other model-based approaches Current practices and gaps in benefit-risk 10:00- Kevin Marsh assessment: opportunities for combining MCDA 10:30 with model-based approaches 10:30- Coffee break, Poster and Software session I 12:00 Page | 1 Posters in Group I (with poster numbers starting with I-) are accompanied by their presenter 12:00- Benefit-risk profile of medicinal Chair: Mats 12:40 products, continued Karlsson 12:00- Neeraj Model-Informed Drug Development (MIDD) for 12:20 Gupta ixazomib, an oral proteasome inhibitor Simulation analysis of absolute lymphocytes 12:20- Nadia counts (ALC) and relapse rate (RR) following 12:40 Terranova cladribine (re-)treatment rules in subjects with relapsing-remitting multiple sclerosis (RRMS) 12:40- Announcement for ACoP8 (2017) Jin Jin 12:45 12:45- Lunch 14:10 14:10- Chair: Lutz Scaling of PD in paediatrics 15:10 Harnisch Scaling pharmacodynamics in children: Lessons 14:10- Joseph from immunology, infectious diseases and 14:50 Standing critical care Scaling renal function in
    [Show full text]
  • HCV Treatment • Characteristics of DAA Classes
    HCV UPDATE Treatment: The Next Wave Access: Myths & Facts NASTAD National Technical Assistance Meeting October 2015 Tracy Swan HCV Treatment • Characteristics of DAA Classes • Next-generation: FDCs • Trends: 3somes and Quickies • HCV Treatment in HIV/HCV DAA CLASSES NON-NUCLEOSIDE POLYMERASE INHIBITORS (Dasabuvir): G1 only, further development/need?? PROTEASE INHIBITORS (Paritaprevir/r, Olysio): Usually G1 and G4, tendency for DDIs, possibly more side effects, resistance may not always be persistent—next generation might be pan-genotypic DAA CLASSES NS5A INHIBITORS (Daclatasvir, Ledipasvir, Ombitasvir, Velpatasvir) : pan/multi-genotypic (less information in G4, G5 and G6)—some DDIs, resistance can persist for >2 years stop them from working--next generation more potent, active against resistance? NUCLEOSIDE/TIDE POLYMERASE INHIBITORS (Sofosbuvir): pan/multi-genotypic (less information in G4, G5 and G6), few DDIs, resistance does not seem to be a major problem; a few more are finally in development Fixed-Dose Combinations (FDCs) WHAT’S HERE NOW…. Sofosbuvir + Ledipasvir Paritaprevir/r + Ombitasvir, w/ Dasabuvir WHAT’S COMING in 2016…. Grazoprevir + Elbasvir Sofosbuvir+ Velpatasvir What’s Coming in 2016 once daily DAA fixed-dose combinations, 12 weeks* Grazoprevir/Elbasvir adults w/ G 1,4 and 6 (TX- naive or -experienced, HIV/HCV; in people w/ cirrhosis or ESRD, and w/OST) ---cure rates generally >90% Sofosbuvir/Velpatasvir adults with all HCV genotypes (TX-naive or -experienced, people with cirrhosis) ---cure rates generally >90% *some
    [Show full text]
  • Genotype 1A – Not Recommended for Decompensated Cirrhosis Paritaprevir/Ritonavir + Ombitasvir + Dasabuvir ± Ribavirin for Genotype 1 HCV 100 97 99 94 99 100 89
    HCV Therapies: State of the Art Elizabeth Verna, MD, MSc Assistant Professor of Medicine Director of Clinical Research, Transplant Initiative Center for Liver Disease and Transplantation Columbia University Learning Objectives • Evaluate the current treatment options for the management of treatment-naive patients with HCV genotype 1 infection • Assess the current treatment options for the management of treatment-experienced patients with HCV genotype 1 infection • Outline the major issues in the current treatment of HCV infection Evolving Landscape of HCV Therapy HCV Approval Approval Approval Antibody pegIFN- alfa- Ledipasvir/Sofosbuvir Approval Telaprevir Testing 2b OBV/PTV/r + DAS Grazoprevir/Elbasvir Boceprevir Genotype-Specific Sofosbuvir/Velpatasvir Discovery of Approval RGT Approval Approval HCV Ribavirin Simeprevir (Chiron) Daclatasvir Sofosbuvir OBV/PTV/r 1989 1992 1998 2001 2005 2011 2013 2014 2015 2016 Current Benchmark >95% SVR: 6% 12% 20% 40% 54% 65–75% >90% pegIFN-alfa 2b = peg-interferon alfa-2b; RGT = response-guided therapy; OBV/PTV/r + DAS = ombitasvir/paritaprevir and ritonavir + dasabuvir (or 3D). Houghton M. Liver Int. 2009;29(Suppl 1):82-88; Carithers RL, et al. Hepatology. 1997;26(3 Suppl 1):S83-S88; Zeuzem S, et al. N Engl J Med. 2000;343(23):1666-1672; Poynard T, et al. Lancet. 1998;352(9138):1426- 1432; McHutchison JG, et al. N Engl J Med. 1998;339(21):1485-1492; Lindsay KL, et al. Hepatology. 2001;34(2):395-403; Fried MW, et al. N Engl J Med. 2002;347(13):975-982; Manns MP, et al. Lancet. 2001;58(9286):958-965; Poordad F, et al. N Engl J Med.
    [Show full text]
  • Hepatitis C Virus Treatment in the Real World: Optimising Treatment and Access to Therapies
    Recent advances in clinical practice Hepatitis C virus treatment in the real world: optimising treatment and access to therapies 1 2 3 4 Editor’s choice Fabien Zoulim, T Jake Liang, Alexander L Gerbes, Alessio Aghemo, Scan to access more 5,6,7,8 9 10 11 free content Sylvie Deuffic-Burban, Geoffrey Dusheiko, Michael W Fried, Stanislas Pol, Jürgen Kurt Rockstroh,12 Norah A Terrault,13 Stefan Wiktor14 For numbered affiliations see ABSTRACT treatments—how can we improve access to diagno- end of article. Chronic HCV infections represent a major worldwide sis and treatment for those patients who need them Correspondence to public health problem and are responsible for a large most? Professor Fabien Zoulim, proportion of liver related deaths, mostly because of Gut brought together some of the leading global Université Lyon 1, Cancer HCV-associated hepatocellular carcinoma and cirrhosis. experts in HCV to discuss these questions and Research Center of Lyon The treatment of HCV has undergone a rapid and point a way forward. The round table, held during (CRCL), INSERM U1052, spectacular revolution. In the past 5 years, the launch of the European Association for the Study of the Hospices Civils de Lyon 69003, ’ France; direct acting antiviral drugs has seen sustained Liver s International Liver Congress 2015, brought [email protected] virological response rates reach 90% and above for clarity to some of these issues and looked into the many patient groups. The new treatments are effective, future pipeline of HCV treatment. This article aims Received 21 July 2015 well tolerated, allow for shorter treatment regimens and to summarise that shared knowledge.
    [Show full text]
  • Direct-Acting Antivirals with Excellent Efficacy and Favourable Safety, Represent a Unique Opportunity to Achieve HCV Elimination
    The French and European Approach Towards Hepatitis C Virus Elimination HEPDART 2017 USA December 3rd, 2017 Tarik Asselah (MD, PhD) Professor of Medicine Hepatology, Chief INSERM UMR 1149, Hôpital Beaujon, Clichy, France. Disclosures • Employee of Paris Public University Hospitals (AP-H P, Beaujon’s Hospital) and University of Paris • Principal investigator for research grants : Funds paid to Hospital (AP-HP) • Consultant, expert and speaker for: Abbvie, Bristol-Myers Squibb, Gilead, Janssen, Merck Sharp Dohme, Roche. • Grants from : ANR, CNRS , INSERM , University of Paris, ANRS 2 The French and European Approach Towards Hepatitis C Virus Elimination The goal of this lecture will be to present the situation of HCV in Europe and in France. Direct-acting antivirals with excellent efficacy and favourable safety, represent a unique opportunity to achieve HCV elimination. We will discuss the European & French approach towards Hepatitis Programs and to identify models to achieve Elimination. The French and European Approach Towards Hepatitis C Virus Elimination 1 Great Drugs (Direct-acting antivirals) 2 Epidemiology : Europe & France 3 HCV management : Europe & France 4 Remaining Challenges 5 Take home messages Direct-acting antivirals : a Revolution 5’NTR Structural proteins Nonstructural proteins 3’NTR Metalloprotease Envelope Serine protease RNA Capsid glycoproteins RNA helicase Cofactors polymerase C E1 E2 NS1 NS2 NS3 NS4A NS4B NS5A NS5B Protease Inhibitors NS5A Inhibitors Polymerase Inhibitors « …previr » « ….asvir » « …..buvir » Telaprevir Daclatasvir Nucs Non-Nucs Boceprevir Ledipasvir Simeprevir Velpatasvir (GS-5816) Sofosbuvir Dasabuvir Paritaprevir Ombitasvir MK 3682 GS-9669 Glecaprevir Pibrentasvir ACH-3422 MK-8876 Grazoprevir Elbasvir ALS-335 Voxilaprevir MK-8408 Sovaprevir Samatasvir ACH-2684 Odalasvir (ACH-3102) Asselah et al.
    [Show full text]
  • Hepatitis Central.Com 2016 Was an Amazing Year for Hepatitis C Drug Progress
    Hepatitis C – Hepatitis Central.Com 2016 was an amazing year for Hepatitis C drug progress. In 2016, Harvoni and Viekira Pak were the most likely prescribed Hepatitis C medications. In addition, Zepatier, Viekira XR, Technivie and Epclusa were approved by the FDA to treat Hepatitis C. Used for different Hepatitis C genotypes, these medications boast a very high success rate, eliminating the Hepatitis C virus in 95 to 100 percent of patients. However, there is always room for improvement. The following pharmaceutical companies are leading the way: Gilead This combination consists of sofosbuvir, velpatasvir and voxilaprevir to treat people who had failed previous therapies and to provide higher cure rates for those who had not been previously treated (genotypes 1 through 6). The cure rates in phase 3 clinical trials were 95 to 98 percent. This led to being granted Breakthrough Therapy designation by the FDA for those with genotype 1 who had failed a previous course of therapy that contained a NS5A inhibitor and being submitted in December 2016 for approval to treat all genotypes. AbbVie The combination of glecaprevir (ABT-493) plus pibrentasvir (ABT-530) was used to treat genotypes 1, 3, 4, 5 and 6 for a duration of just eight weeks. This combination was granted Breakthrough Therapy designation by the FDA for those with genotype 1 who had failed a previous course of therapy that contained a NS5A inhibitor. In December 2016 AbbVie applied to the FDA to market and treat all Hepatitis C genotypes with this drug combination. Janssen • Samatasvir – currently in phase 1 development for genotypes 1, 2, 3 and 4, and in a phase II study with Olysio (simeprevir) in treatment-naı̈ve patients with genotype 1b or 4.
    [Show full text]
  • Hepatitis C Treatment: Where Are We Now?
    Journal name: International Journal of General Medicine Article Designation: REVIEW Year: 2017 Volume: 10 International Journal of General Medicine Dovepress Running head verso: Burstow et al Running head recto: Hepatitis C treatment open access to scientific and medical research DOI: http://dx.doi.org/10.2147/IJGM.S127689 Open Access Full Text Article REVIEW Hepatitis C treatment: where are we now? Nicholas J Burstow1 Abstract: Chronic hepatitis C infection affects millions of people worldwide and confers sig- Zameer Mohamed1 nificant morbidity and mortality. Effective treatment is needed to prevent disease progression and Asmaa I Gomaa2 associated complications. Previous treatment options were limited to interferon and ribavirin (RBV) Mark W Sonderup3 regimens, which gave low cure rates and were associated with unpleasant side effects. The era of Nicola A Cook1 direct-acting antiviral (DAA) therapies began with the development of first-generation NS3/4A protease inhibitors in 2011. They vastly improved outcomes for patients, particularly those with Imam Waked2 genotype 1 infection, the most prevalent genotype globally. Since then, a multitude of DAAs have C Wendy Spearman3 been licensed for use, and outcomes for patients have improved further, with fewer side effects and 1 Simon D Taylor-Robinson cure rates approaching 100%. Recent regimens are interferon-free, and in many cases, RBV-free, 1 For personal use only. Liver Unit, Department of Surgery and involve a combination of DAA agents. This review summarizes the treatment options
    [Show full text]
  • 13. Approved and Experimental Therapies
    APPROVED AND EXPERIMENTAL THERAPIES FOR TREATMENT OF HEPATITIS B AND C, AND MUTATIONS 13. ASSOCIATED WITH DRUG RESISTANCE • Luis Menéndez-Arias HEPATITIS B Table 13.1. CURRENT DRUGS FOR TREATMENT OF HEPATITIS B Drug name Drug class Manufacturer Status Pegasys (peginterferon α-2a) Interferon Genentech FDA-approved Intron A (interferon a-2b) Interferon Merck FDA-approved Hepsera (adefovir Nucleotide analogue Gilead Sciences FDA-approved dipivoxil)a Viread (tenofovir Nucleotide analogue Gilead Sciences FDA-approved b disoproxil fumarate) a Epivir-HBV, Zeffix and Nucleoside analogue Glaxo SmithKline FDA-approved Heptodin (lamivudine) a Baraclude (entecavir) Nucleoside analogue Bristol-Myers Squibb FDA-approved Tyzeka, Sebivo Nucleoside analogue Novartis FDA-approved (telbivudine) Vemlidy (TAF, tenofovir Tenofovir prodrug Gilead Sciences FDA-approved alafenamide, GS-7340) Emtriva (emtricitabine; Nucleoside analogue Gilead Sciences FDA-approved b FTC) a Levovir, Revovir Nucleoside analogue Bukwang Studies cancelled c (clevudine, L-FMAU) pharmaceuticals, Eisai (Japan) Besivo (LB80380, Nucleoside analogue IIDong Pharmaceutical Approved in S ANA380) Co. Ltd. Korea Zadaxin (thymosin alpha) Immune enhancer SciClone Approved outside U.S. ABX 203 Therapeutic vaccine ABIVAX Phase IIb/III ARC-520 RNAi gene silencer Arrowhead Research Phase II/III 641 Drug name Drug class Manufacturer Status Myrcludex B Entry inhibitor Hepatera (Russia), Phase IIa Myr-Gmbh (Germany) (Russia) NVR-1221 (NVR 3-778) Capsid inhibitor Novira Therapeutics Phase IIa AGX-1009
    [Show full text]
  • Stembook 2018.Pdf
    The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances FORMER DOCUMENT NUMBER: WHO/PHARM S/NOM 15 WHO/EMP/RHT/TSN/2018.1 © World Health Organization 2018 Some rights reserved. This work is available under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization. Suggested citation. The use of stems in the selection of International Nonproprietary Names (INN) for pharmaceutical substances. Geneva: World Health Organization; 2018 (WHO/EMP/RHT/TSN/2018.1). Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data.
    [Show full text]
  • Therapeutic Strategies for Recent Hepatitis C Virus Infection in the Era of Direct-Acting Antiviral Therapy
    Therapeutic strategies for recent hepatitis C virus infection in the era of direct-acting antiviral therapy Marianne Martinello A thesis in fulfilment of the requirements for the degree of Doctor of Philosophy The Kirby Institute Faculty of Medicine May 2017 Page 1 of 309 Thesis/Dissertation Sheet THE UNIVERSITY OF NEW SOUTH WALES Thesis/Dissertation Sheet Surname or Family name: Martinello First name: Marianne Abbreviation for degree as given in the University calendar: PhD School: Kirby Institute Faculty: Medicine Title: Therapeutic strategies for recent hepatitis C virus infection in the era of direct-acting antiviral therapy Abstract: Background: The management of recent hepatitis C virus (HCV) infection is uncertain, as the therapeutic landscape evolves with the advent of direct-acting antiviral (DAA) therapy. Aims: The broad aim of this research was to examine novel therapeutic strategies in recent HCV following the availability of DAA therapy. Specific aims included assessing the feasibility, efficacy and safety of response-guided interferon (IFN) -containing and ultra-short IFN-free therapy; calculating reinfection incidence following treatment; and determining the clinical significance of drug-drug interactions in HIV/HCV co-infection. Methods: In Chapters Two and Three, the efficacy and safety of short and/or response-guided treatment among individuals with recent HCV was examined in three open-label trials: ATAHC II (n=52; pegylated-IFN +/- ribavirin), DARE-C I (n=14; pegylated-IFN, ribavirin + telaprevir) and DARE-C II (n=19; sofosbuvir + ribavirin). In Chapter Four, reinfection incidence following treatment for recent HCV was calculated among those who achieved an end-of-treatment response in ATAHC I and II, DARE-C I and II (n=120).
    [Show full text]
  • The Liver Week 2016-6차.Hwp
    Special Lecture 2. Special Lecture 2. Hepatitis C Virus: Next Generation of DAAs Mark Sulkowski Professor of Medicine Divisions of Infectious Diseases and Gastroenterology/Hepatology Johns Hopkins University School of Medicine Medical Director, Viral Hepatitis Center Johns Hopkins Hospital Baltimore Maryland USA In the current era, multiple HCV treatment regimens have been developed that are interferon-free and deliver high rates of HCV cure (> 95%) in most patient populations with treatment durations in the range of 12 weeks. In the context, the question can and should be asked: Is there a medical need for a next generation of DAAs. In short, the answer is that novel drugs and drug regimens are needed for certain patient populations including 1) Person who failed to achieve HCV cure with current DAAs need “salvage” regimens that can overcome HCV drug resistance associated variants (RAVs); 2) HCV genotype 3 for whom the treat- ment options are limited; 3) Persons for whom ribavirin is still recommended including those with HCV genotype 2 and some patients with cirrhosis. HCV NS3 Protease inhibitors. The first wave of HCV protease inhibitors – telaprevir, boceprevir and simeprevir – are not pan- genotypic, lacking potent antiviral activity against HCV genotype 3. There are two protease inhibitors in phase 3 clinical trials that are once daily, potent, pangenotypic drugs: Voxilaprevir (VOX, GS-9857) and ABT-493. Voxilaprevir is being developed as a fixed-dose combination tablet including sofosbuvir and velpatasvir (a pangenotypic NS5A inhibitor). ABT-493 is being devel- oped as a fixed-dose combination tablet including ABT-530 (a pangenotypic NS5A inhibitor). Both regimens are currently being evaluated in phase 3 clinical trials for treatment durations of 8 and 12 weeks in persons with all HCV genotypes and in those who failed DAA regimens.
    [Show full text]
  • Review : Imunoterapi Penanganan Infeksi Virus
    Jurnal Mandala Pharmacon Indonesia, Vol 7.No.1 Juni 2021 Avaiable online at www.jurnal-pharmaconmw.com/jmpi p-ISSN : 2442-6032 e-ISSN : 2598-9979 Review : Imunoterapi Penanganan Infeksi Virus Usmar1, Andi Maqhfirah Nurul Fitri1, Dewi Yuliana2, Firzan Nainu1* 1Fakultas Farmasi, Universitas Hasanuddin, Makassar 2Fakultas Farmasi, Universitas Muslim Indonesia, Makassar ABSTRAK Penyakit menular akibat virus merupakan salah satu perkembangan yang pesat terutama dalam kondisi masalah kesehatan global yang mempengaruhi sistem pandemi COVID-19 yang dihadapi saat ini. Meskipun kesehatan masyarakat dan ekonomi di seluruh dunia. terapi dan obat-obatan yang digunakan dalam bidang Hal tersebut mendorong disusunnya artikel ini untuk imunofarmakologi masih terbatas serta banyak hal yang mendiskusikan relevansi dan pentingnya imunoterapi belum dapat ditemukan, namun teknologi baru dan dalam menentukan pilihan terapetik terkait infeksi kemajuan pesat dalam pengetahuan tentang regulasi virus, dengan menitikberatkan pembahasan pada sistem imun telah menjadikan imunoterapi sebagai ketersediaan pilihan vaksin dan obat yang telah bidang yang memiliki potensi besar dan menjanjikan ditemukan untuk membantu manusia melawan berbagai dalam penanganan infeksi virus maupun patogen lain. jenis infeksi yang disebabkan oleh virus. Penulisan Oleh karena itu, konsep imunoterapi serta relevansinya artikel review naratif ini dilakukan menggunakan dengan penyakit manusia merupakan salah satu solusi metode analisis pustaka primer maupun sekunder yang menawarkan pilihan baru
    [Show full text]