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Segunda Jornada sobre TRATAMIENTO DE LAS HEPATITIS C EN COINFECTADOS CON VIH Barcelona, jueves 8 de octubre de 2015 El paciente con genoRpo 4. Mª Jesús Téllez Medicina Interna/Unidad VIH Hospital Clínico San Carlos Madrid VIRUS HEPATITIS C GENOTIPO 4 • • • • • INTRODUCCION: EPIDEMIOLOGIA TRATAMIENTO HASTA 2015 TRATAMIENTO EN 2015 FUTURO PROXIMO RESUMEN VIRUS HEPATITIS C GENOTIPO 4 • • • • • INTRODUCCION: EPIDEMIOLOGIA TRATAMIENTO HASTA 2015 TRATAMIENTO EN 2015 FUTURO PROXIMO RESUMEN Prevalencia relaRva de cada genoRpo de VHC . 2-‐3% de la población infectada por VHC 130–180 millones de personas están infectadas con el virus de la hepaRRs C (VHC) Messina JP et al. Hepatology, 2015; 61: 77-‐87 Hanafiah MK et al Hepatology, 2013; 57:1333-‐42 Prevalencia de GT-‐4 del Virus de la HepaRRs C GT 4 representa el 13% de las infecciones Egipto Rene la mayor prevalencia de infección por VHC (15%) y el 90% son GT-‐4 Messina JP et al. Hepatology, 2015; 61: 77-‐87 Hanafiah MK et al Hepatology, 2013; 57:1333-‐42 1.De Brujine et al. J Clin Microbiolo. 2009; 47: 3832-‐8 2. Antaki N et al. Liver Int. 2010; 30:342-‐55 Adapted from Harizadeh et al. Nat Rev. Gastroenterol Hepatol 2013; 10: 553-‐62 3. Echevarria JM et al. Enferm Infecc Microbiol Clin 2006; 24:20-‐25 VIRUS HEPATITIS C GENOTIPO 4 • • • • • INTRODUCCION: EPIDEMIOLOGIA TRATAMIENTO HASTA 2015 TRATAMIENTO EN 2015 FUTURO PROXIMO RESUMEN Prehistoria del tratamiento del VHC GT-‐4 Tasa de respuesta a IFN RBV entre GT 1 y GT 2 y3 70% moderada a severa esteatosis Kamal SM et al. Hepatology, 2008; 47: 1371-‐83 RESPUESTA A INF RBV EN VIDA REAL. ESTUDIO PROPHESYS • Cohorte internacional • N 7163 • GT4 317 Marcelin P et al. Hepatology. 2012;56:2039-‐50. Historia reciente del tratamiento del Virus de la hepaRRs C GT-‐4, converRda en prehistoria • • • • EC Fase 3, abierto N=107 35% cirroRcos SMV +PR según TGR (24-‐48s) Moreno . EASL 2014. Poster 1319 Abstract BACKGROUND: Treatment opRons for HCV genotype 4 (GT4) are limited. This phase 3 study (COMMAND-‐4; AI444-‐042) evaluated the efficacy and safety of daclatasvir (DCV), a pan-‐genotypic HCV NS5A inhibitor, with peginterferon-‐alfa-‐2a/ribavirin (pegIFN/RBV) in treatment-‐naive paRents with HCV GT4 infecRon. METHODS: PaRents were randomly assigned (2:1; blinded) to treatment with DCV 60 mg (n = 82) or placebo (n = 42) once daily plus pegIFN 180 µg weekly and RBV 1000-‐1200 mg/day (weight-‐ based) twice daily. DCV-‐treated paRents with undetectable HCV RNA at weeks 4 and 12 (eRVR) received 24 weeks of DCV plus pegIFN/RBV; those without eRVR received an addiRonal 24 weeks of pegIFN/RBV. All placebo-‐treated paRents received 48 weeks of pegIFN/RBV. The primary endpoint was SVR at post-‐treatment week 12 (SVR12). RESULTS: PaRents were 75% IL28B non-‐CC and 11% had cirrhosis. SVR rates (HCV RNA <LLOQ) at post-‐ treatment week 12 or later (imputed to include paRents missing SVR12 assessments but had SVR axer post-‐treatment week 12) were 82% (67/82) with DCV plus pegIFN/RBV vs 43% (18/42) with pegIFN/RBV (p <0.0001).In DCV recipients, SVR12 rates were comparable across subgroups. The safety and tolerability profile of DCV plus pegIFN/RBV was comparable to that of pegIFN/RBV. DisconRnuaRons due to AEs occurred in 4.9% of paRents receiving DCV plus pegIFN/RBV and 7.1% of paRents receiving pegIFN/RBV. CONCLUSIONS: In treatment-‐naive paRents with HCV GT4 infecRon, DCV plus pegIFN/RBV achieved higher SVR12 rates than pegIFN/RBV alone. These data support DCV-‐based regimens for treatment of HCV GT4 infecRon, including all-‐oral combinaRons with other direct-‐acRng anRvirals. (AI444-‐042; ClinicalTrials.gov NCT01448044). Historia reciente del tratamiento del Virus de la hepaRRs C GT-‐4, converRda en prehistoria Estudio Command 4 • EC Fase 3, Randomizado 2:1 , controlado con PLB • N= 124 • Naives, cirroRcos 11% • DCV PR según TGR (24-‐48s) Hezode C. IDWeek 2014. Philadelphia, PA, October 8–12, 2014. Abstract 819 VIRUS HEPATITIS C GENOTIPO 4 • • • • • INTRODUCCION: EPIDEMIOLOGIA TRATAMIENTO HASTA 2015 TRATAMIENTO EN 2015 FUTURO PROXIMO RESUMEN GUIAS DE TRATAMIENTO DEL GT 4 DEL VIRUS DE LA HEPATITIS C (OCT/2015) GeSIDA/GEHEP EASLD AASLD/ IAS-‐USA LDV/SOF No Ci Cirrosis 12s (AI) 12s (A1) 12s + R (BIII) o 24s+R 12s +R o 24 s sin R (B1) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Pr/O +R No Ci Cirrosis 12s (AI) 24s (BIII) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + R -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + PR -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12 s (A1) 12s (IIa/B) SOF + DCV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + SMV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (A1) 24s (B1) 24s (IIa/B) LDV: Ledipasvir. SOF: sofosbuvir. Pr :Paritaprevir ritonavir. O: Ombitasvir. PR: Interferon pegilado Ribavirina. DCV: Daclatasvir. SMV: Simeprevir GUIAS DE TRATAMIENTO DEL VIRUS DE LA HEPATITIS C (OCT/2015) GeSIDA/GEHEP LDV/SOF No Ci Cirrosis EASLD AASLD/ IAS-‐USA 12s (AI) 12s (A1) 12s + R (BIII) o 24s+R 12s +R o 24 s sin R (B1) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Pr/O +R No Ci Cirrosis 12s (AI) 24s (BIII) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + R -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + PR -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12 s (A1) 12s (IIa/B) SOF + DCV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + SMV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (A1) 24s (B1) 24s (IIa/B) LDV: Ledipasvir. SOF: sofosbuvir. Pr :Paritaprevir ritonavir. O: Ombitasvir. PR: Interferon pegilado Ribavirina. DCV: Daclatasvir. SMV: Simeprevir ESTUDIO SYNERGY: Ledipasvir and sofosbuvir for hepaRRs C genotype 4: a proof-‐of-‐concept • Fase 2, un centro • N 21, VHC GT 4 13(6%) naive 8(38%) preTTº • CH 7 (33%) • No VIH o VHB • SOF/LDV 12 s • End piont RVS12 Kohli A et al Lancet Infect Dis. 2015;15:1049-‐54 LEDIPASVIR/SOFOSBUVIR PARA EL TRATAMIENTO DE PACIENTES CON INFECCION POR VHC GT 4 y 5 • Ensayo abierto Fase 2b, Francia. GT4 y 5 • N=44 GT 4 • Naive y pretratados • CirroRcos compensados , 10 p • LDV/SOF 12 s • End point RVS12 Abergel A et al. EASLD, Viena 2015 LEDIPASVIR/SOFOSBUVIR PARA EL TRATAMIENTO DE PACIENTES CON INFECCION POR VHC GT 4 y 5 RVS12 según Historia de tratamiento y de Cirrosis 3 recidivas 1 naive 2 pretratados con IP (BOC y TVP) no cirroRcos Abergel A et al. EASLD, Viena 2015 SOLAR-‐2 study:Ledipasvir/ sofosbuvir en CirroRcos pre y postrasplante VHC GT 1 y 4 Fase 2 , abierto, randomizado. Dos cohortes: A: CH Child B o C preTX B: Postrasplante GT 1 o 4, naives o preqo (≈80%) N 329 No VIH o VHB No previo uso inh NS5A SOF/LDV +R 12s vs 24s End point : RVS 12s Charlton M, et al. Gastroenterology. 2015; 149:649-‐59. SVR12 by Genotype GT 1 and GT 4 LDV/SOF + RBV 12 Weeks 24 Weeks GT 4 SVR12 (%) GT 1 72/75 57/58 F0-F3 & CPT A 57/65 54/61 CPT B & C 10/11 7/7 F0-F3 & CPT A 4/7 6/7 CPT B & C Charlton M, et al. Gastroenterology. 2015; 149:649-‐59. 20 20 SVR12 by Genotype GT 1 and GT 4 LDV/SOF + RBV 12 Weeks 24 Weeks SVR12 (%) GT 1 1 relapse 2 deaths 72/75 1 death 57/58 F0-F3 & CPT A GT 4 4 relapse 4 deaths 57/65 2 relapse 4 deaths 1 w/d consent 1 death 54/61 10/11 CPT B & C 3 relapse 7/7 F0-F3 & CPT A 4/7 1 death 6/7 CPT B & C Charlton M, et al. Gastroenterology. 2015; 149:649-‐59. 21 21 GUIAS DE TRATAMIENTO DEL GT4 DEL VIRUS DE LA HEPATITIS C (OCT/2015) GeSIDA/GEHEP EASLD AASLD/ IAS-‐USA LDV/SOF No Ci Cirrosis 12s (AI) 12s (A1) 12s + R (BIII) o 24s+R 12s +R o 24 s sin R (B1) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Pr/O +R No Ci Cirrosis 12s (AI) 24s (BIII) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + R -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + PR -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12 s (A1) 12s (IIa/B) SOF + DCV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + SMV No Ci Cirros -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (A1) 24s (B1) 24s (IIa/B) LDV: Ledipasvir. SOF: sofosbuvir. Pr :Paritaprevir ritonavir. O: Ombitasvir. PR: Interferon pegilado Ribavirina. DCV: Daclatasvir. SMV: Simeprevir PEARL-‐I: Efficacy of OBV/PTV/r (2D) + RBV in Treatment-‐ Naïve and Treatment-‐Experienced Non-‐cirrhoRc Subjects with GT4 InfecRon . • EC fase 2b , mulRcentrico • Abierto, Randomizado en naive 1:1 a 2D ± R 12 s • Todos los preTTº: 2D + R • N = 135 • F0-‐F1: 67%-‐ 86% • No VIH • 3 pacientes fracasaron en 2D sin R • 1 paciente carece de datos a semana 12 posTTº Hézode C et al. Lancet. 2015;385:2502-‐9. GUIAS DE TRATAMIENTO DEL GT 4 DEL VIRUS DE LA HEPATITIS C (OCT/2015) GeSIDA/GEHEP EASLD AASLD/ IAS-‐USA LDV/SOF No Ci Cirrosis 12s (AI) 12s (A1) 12s + R (BIII) o 24s+R 12s +R o 24 s sin R (B1) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Pr/O +R No Ci Cirrosis 12s (AI) 24s (BIII) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + R -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + PR -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12 s (A1) 12s (IIa/B) SOF + DCV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + SMV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (A1) 24s (B1) 24s (IIa/B) LDV: Ledipasvir. SOF: sofosbuvir. Pr :Paritaprevir ritonavir. O: Ombitasvir. PR: Interferon pegilado Ribavirina. DCV: Daclatasvir. SMV: Simeprevir SOFOSBUVIR Y RIBAVIRINA EN GT4 EN PACIENTES DE ORIGEN EGIPCIO Fase 2, abierto, randomizado, 1:1 a SOF/RBV 12 vs 24 s N 103;. Naives y pretratados 17% Cirrosis ESTUDIOS PHOTON 1 Y 2 PACIENTES COINFECTADOS VHC/VIH GT 1-‐4 • GT4 24 s SOF RBV SVR12 (%) • ECs FASE 3, Abiertos • N 497, GT4 31 • Cirrosis 15% 182/226 40/45 GT 1 TN 24 Weeks 27/30 26/31 GT 2 TN 12 Weeks GT 2 TE 24 Weeks GT 4 TN 24 Weeks 1 (2) 2 (7) 5 (16) Relapse, n (%) 39 (17) Breakthrough, n (%) 1 (<1) 1 (2) 0 0 Lost to follow-‐up, n (%) 2 (<1) 1 (2) 0 0 Withdrew consent, n (%) 2 (<1) 2 (4) 1 (3) 0 26 Rosktroh J. AASLD Boston 2014 GUIAS DE TRATAMIENTO DEL GT4 DEL VIRUS DE LA HEPATITIS C (OCT/2015) GeSIDA/GEHEP EASLD AASLD/ IAS-‐USA LDV/SOF No Ci Cirrosis 12s (AI) 12s (A1) 12s + R (BIII) o 24s+R 12s +R o 24 s ± R (B1) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Pr/O +R No Ci Cirrosis 12s (AI) 24s (BIII) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + R -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + PR -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12 s (A1) 12s (IIa/B) SOF + DCV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + SMV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (A1) 24s (B1) 24s (IIa/B) LDV: Ledipasvir. SOF: sofosbuvir. Pr :Paritaprevir ritonavir. O: Ombitasvir. PR: Interferon pegilado Ribavirina. DCV: Daclatasvir. SMV: Simeprevir Sofosbuvir + PEG + RBV en pacientes con VHC , Naive a tratamiento y GenoRpos 1, 4, 5 y 6. Ensayo NEUTRINO • Fase 3 , mulRcentrico • Abierto, un solo brazo • N= 327 , Cirrosis 17% • Naives • GT 4 9% (28) • SOF PR 12s • End point RVS12s Lawitz E et al. N Engl J Med. 2013;368:1878-‐87. GUIAS DE TRATAMIENTO DEL GT4 DEL VIRUS DE LA HEPATITIS C (OCT/2015) GeSIDA/GEHEP EASLD AASLD/ IAS-‐USA LDV/SOF No Ci Cirrosis 12s (AI) 12s (A1) 12s + R (BIII) o 24s+R 12s +R o 24 s sin R (B1) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ Pr/O +R No Ci Cirrosis 12s (AI) 24s (BIII) 12s (IIa/B) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + R -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + PR -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12 s (A1) 12s (IIa/B) SOF + DCV No Ci Cirrosis -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ 12s (B2) 12s +R o 24 s sin R (B2) -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ -‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐-‐ SOF + SMV No Ci Cirrosis 12s (A1) 24s (B1) 24s (IIa/B) LDV: Ledipasvir. SOF: sofosbuvir. Pr :Paritaprevir ritonavir. O: Ombitasvir. PR: Interferon pegilado Ribavirina. DCV: Daclatasvir. SMV: Simeprevir Efficacy of the oral Sofosbuvir-‐based combinaGon in HCV genotype 4-‐monoinfected paGents from the French observaGonal cohort ANRS CO22 HEPATHER 12s 24s SOD DCV 16/18 (89%) 4/4 (100%) SOF DCV R 3/3 (100%) 4/4 (100%) SOF SMV 8/8 (100%) 10/11(89%) SOF SMV R 1/1 (100%) 6/6 (100%) Fontain H et al . EASL 2015, Viena DACLATASVIR PLUS SOFOSBUVIR WITH OR WITHOUT RIBAVIRIN IN PATIENTS WITH HIV-‐HCV COINFECTION: INTERIM ANALYSIS OF A FRENCH MULTICENTER COMPASSIONATE USE PROGRAM Fontain H et al . EASL 2015, Viena Safety and effecRveness of sofosbuvir-‐based regimens for the treatment of hepaRRs C genotype 3 and 4 infecRons: interim analysis of a prospecRve observaRonal study: COHORTE TARGET Alqahtani S et al. EASL 2015; abstract P0840 Safety and effecRveness of sofosbuvir-‐based regimens for the treatment of hepaRRs C genotype 3 and 4 infecRons: interim analysis of a prospecRve observaRonal study: COHORTE TARGET Alqahtani, S., et al.:EASL 2015; abstract P0840 VIRUS HEPATITIS C GENOTIPO 4 • • • • • INTRODUCCION: EPIDEMIOLOGIA TRATAMIENTO HASTA 2015 TRATAMIENTO EN 2015 FUTURO PROXIMO RESUMEN THE PHASE 3 C-‐EDGE TREATMENT-‐NAIVE (TN) STUDY OF A 12-‐WEEK ORAL REGIMEN OF GRAZOPREVIR (GZR, MK-‐5172)/ELBASVIR (EBR, MK-‐8742) IN PATIENTS WITH CHRONIC HCV GENOTYPE (GT) 1, 4, OR 6 INFECTION Zeuzem S. ILC Viena 2015 Figure 36: SVR12 rates in the C-‐EDGE TN study Zeuzem S. ILC Viena 2015 C-‐EDGE COINFECTION: PHASE 3 STUDY OF GRAZOPREVIR/ ELBASVIR IN PATIENTS WITH HCV/HIV *1 paRent with GT6 infecRon and 1 paRent with GT1 not-‐otherwise subtyped were also included; both paRents achieved SVR12. Rockstroh JK, et al, The Lancet HIV 2015, 2(8):e319-‐e327 VIRUS HEPATITIS C GENOTIPO 4 • • • • • INTRODUCCION: EPIDEMIOLOGIA TRATAMIENTO HASTA 2015 TRATAMIENTO EN 2015 FUTURO PROXIMO RESUMEN Estudios en VHC GenoGpo 4 Estudio Diseño, población Pauta Resultado (RVS12) ITT Synergy Fase 2, abierto, USA, Naive y PreT. 33% F4 LDV/SOF 12s 95% (20 /21) Kapoor R. AASLD 2014 ESTUDIO FRANCES Fase 2, abierto, Fancia LDV/SOF 12s Naives 22 (96%) Ci10(100%) Preqo 22 (91%) Abergel A. EASLD 2015 PEARL-‐I Fase 2b, abierto, internacional, Naives y preqo No Ci PTVr/OBV+R Naives 42 (100%) Preqo 42 (100%) Hezode C. Lancet 2015 Solar-‐2 Fase 2, abierto, Int. CH descomp y postTX (F0-‐F3 A CHILD C) LDV/SOF +R 12 o 24 s PosTX (F0-‐3 Child A) 10/11 (91%) vs 7/7 (100%) PostTX Child B, C 4/7(57%) vs 6/7 (86%) Charlton M. Gastroent erology. 2015 Neutrino Fase 3, abierto, naives CH 17%, SOF PR 12s 27/28 (90%) Lawitz E et al. N Engl J Med.2013; Pacientes egipcios Fase 3. Abierto, Intern. SOF RBV 24s Naive (VIH +) 84% (36/31) CH 88% (7/8 ) Roskstroh AASLD 2014 RecruiGng A Study of the Efficacy and Safety of PPI-‐668 (NS5A Inhibitor) Plus Sofosbuvir, With or Without Ribavirin, in PaGents With Chronic HepaGGs C Genotype-‐4 CondiGon:Chronic HepaRRs CIntervenGons:Drug: ravidasvir hydrochloride; Drug: sofosbuvir; Drug: ribavirin RecruiGng A Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With Ribavirin in Adults With Genotype 1 and Ombitasvir/Paritaprevir/Ritonavir With Ribavirin in Adults With Genotype 4 Chronic HepaGGs C Virus InfecGon and Decompensated Cirrhosis CondiGons:Chronic HepaRRs C; Decompensated Cirrhosis; HepaRRs C VirusIntervenGons:Drug: ABT-‐450/ ritonavir/ABT-‐267; Drug: ABT-‐333; Drug: Ribavirin RecruiGng A Randomized, Open-‐Label Study to Evaluate the Safety and Efficacy of Ombitasvir/ABT-‐450/Ritonavir Co-‐administered With Ribavirin (RBV) in Adults With Genotype 4 Chronic HepaGGs C Virus (HCV) InfecGon and Cirrhosis (AGATE-‐1) CondiGon:HepaRRs C VirusIntervenGons:Drug: ombitasvir/ABT-‐450/ritonavir; Drug: Ribavirin RecruiGng A Two Part, Open-‐label Study to Evaluate the Safety and EffecGveness of ABT-‐450/r/ABT-‐267 or ABT-‐450/r/ABT-‐267 and ABT-‐333 Given With or Without a Drug Called Ribavirin in People With Both HepaGGs C Virus Genotype 1 or 4 InfecGon and Human Immunodeficiency Virus, Type 1 InfecGon CondiGons:HepaRRs C Virus InfecRon; Human Immunodeficiency Virus InfecRon; Chronic HepaRRs C; Compensated Cirrhosis and Non-‐ cirrhoRcsIntervenGons:Drug: ABT-‐450/r/ABT-‐267; Drug: ABT-‐333; Drug: Ribavirin (RBV RecruiGng A Study to Evaluate Treatment of HepaGGs C Virus InfecGon in Pediatric Subjects CondiGon:Chronic HepaRRs C InfecRonIntervenGons:Drug: ombitasvir; Drug: paritaprevir; Drug: ritonavir; Drug: dasabuvir; Drug: ribavirin RecruiGng Simeprevir in CombinaGon With Sofosbuvir in Treatment-‐Naïve or -‐Experienced Adults With Chronic Genotype 4 HepaGGs C Virus InfecGon CondiGon:Chronic HepaRRs CIntervenGons:Drug: Simeprevir; Drug: Sofosbuvir Not yet recruiGng Ombitasvir/Paritaprevir/Ritonavir With or Without Dasabuvir in Adults With Genotype 1a or Genotype 4 Chronic HepaGGs C Virus (HCV) InfecGon, With Severe Kidney Impairment or End Stage Kidney Disease CondiGons:HCV; Genotype 1a; Genotype 4; Chronic Kidney Disease; HepaRRs CIntervenGons:Drug: Ombitasvir/Paritapr RecruiGng Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose CombinaGon, With or Without Ribavirin, in EgypGan Adults With Chronic Genotype 4 HCV InfecGon CondiGon:HepaRRs C Virus InfecRonIntervenGons:Drug: LDV/SOF; Drug: RB Not yet recruiGng Pilot Study to Assess Efficacy and Safety of a Triple Therapy With Asunaprevir, Daclatasvir, and BMS-‐791325 in HCV Genotype 4-‐infected PaGents Ajer Failure of Pegylated Interferon-‐Ribavirin Regimen CondiGon:HepaRRs C Virus Genotype 4 InfecRonIntervenGon:Drug: .Asunaprevir, Daclatasvir and BMS -‐ 791325 RecruiGng Efficacy and Safety of Grazoprevir (MK-‐5172) and MK-‐3682 With Elbasvir (MK-‐8742) or MK-‐8408 for Chronic HepaGGs C Genotype (GT) 1, 2, and 4 InfecGon (MK-‐3682-‐011) CondiGon:HepaRRs CIntervenGons:Drug: Grazoprevir; Drug: MK-‐3682; Drug: Elbasvir; Drug: MK-‐8408 RecruiGng A Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/r With or Without Dasabuvir and With Ribavirin in Chronic HepaGGs C Virus Genotype 1 or 4 Infected Adults With Successfully Treated Early Stage Hepatocellular Carcinoma CondiGon:Chronic HepaRRs C InfecRonIntervenGons:Drug: Ombitasvir/Paritaprevir/Ritonavir; Drug: Dasabuvir; Drug: Ribavirin RecruiGng An Efficacy, Safety and PharmacokineGcs Study of Simeprevir, Daclatasvir and Sofosbuvir in ParGcipants With Chronic HepaGGs C Virus Genotype 1 or 4 InfecGon and Decompensated Liver Disease CondiGon:HepaRRs C, ChronicIntervenGons:Drug: Simeprevir; Drug: Daclatasvir; Drug: Sofosbuvir 135 Not yet recruiGng A Phase 2b EvaluaGon of Daclatasvir/Sofosbuvir in Non-‐CirrhoGc Treatment Naive Subjects With Genotype 1, 2, 3 and 4 Chronic HepaGGs C Virus Coinfected With Human Immunodeficiency Virus (HIV-‐1) CondiGon:HepaRRs CIntervenGons:Drug: Daclatasvir; Drug: Sofosbuvir RecruiGng Safety and Efficacy of Ledipasvir/Sofosbuvir (LDV/SOF) Fixed-‐Dose CombinaGon (FDC) for 6 Weeks in Adults With Acute Genotype 1 or 4 HepaGGs C Virus (HCV) and Chronic Human Immunodeficiency Virus (HIV)-‐1 Co-‐InfecGon CondiGon:HepaRRs C InfecRon With HIV Co-‐InfecRonIntervenGon:Drug: LDV/SO Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose CombinaGon Administered in PaGents Infected With Chronic Genotype 1 or 4 HCV for Use in the Peri-‐OperaGve Liver TransplantaGon Sekng CondiGon:HepaRRs C Virus InfecRonIntervenGon:Drug: LDV/SOF RESUMEN • El GT4 representa una proporción importantante de las infecciones por VHC , la segunda en frecuencia entre los pacientes coinfectados en nuestro país. • Escaso numero de pacientes en escasos ensayos clínicos limitan las recomendacones del tratamiento del GT4. • N o h a y d a t o s s u fi c i e n t e s p a r a r e a l i z a r recomendaciones en pacientes con GT4 y cirrosis. • Se realiza extrapolacion de los resultados en GT 1 en las recomendaciones
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