PMID- 31714950 OWN - NLM STAT- MEDLINE DCOM- 20200320 LR - 20211204 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 14 IP - 11 DP - 2019 TI - Real-world evidence of the effectiveness of ombitasvir-paritaprevir/r +/- dasabuvir +/- ribavirin in patients monoinfected with chronic hepatitis C or coinfected with human immunodeficiency virus-1 in Spain. PG - e0225061 LID - 10.1371/journal.pone.0225061 [doi] LID - e0225061 AB - AIM: We describe the effectiveness and safety of the interferon-free regimen ombitasvir/paritaprevir/ritonavir plus dasabuvir with or without ribavirin (OBV/PTV/r +/- DSV +/- RBV) in a nationwide representative sample of the hepatitis C virus (HCV) monoinfected and human immunodeficiency virus-1/hepatitis C virus (HIV/HCV) coinfected population in Spain. MATERIAL AND METHODS: Data were collected from patients infected with HCV genotypes 1 or 4, with or without HIV-1 coinfection, treated with OBV/PTV/r +/- DSV +/- RBV at 61 Spanish sites within the initial implementation year of the first government-driven "National HCV plan." Effectiveness was assessed by sustained virologic response at post-treatment week 12 (SVR12) and compared between monoinfected and coinfected patients using a non-inferiority margin of 5% and a 90% confidence interval (CI). Sociodemographic and clinical characteristics or patients and adverse events (AEs) were also recorded. RESULTS: Overall, 2,408 patients were included in the intention-to-treat analysis: 386 (16%) were patients with HIV/HCV. Patient selection reflected the real distribution of patients treated in each participating region in Spain. From the total population, 96.6% (95% CI, 95.8-97.3%) achieved SVR12. Noninferiority of SVR12 in coinfected patients was met, with a difference between monoinfected and coinfected patients of -2.2% (90% CI, -4.5% - 0.2%). Only genotype 4 was associated with non-response to OBV/PTV/r +/- DSV +/- RBV treatment (p<0.001) in the multivariate analysis. Overall, 286 patients (11.9%) presented AEs potentially related to OBV/PTV/r +/- DSV, whereas 347 (29.0%) presented AEs potentially related to ribavirin and 61 (5.1%) interrupted ribavirin. CONCLUSIONS: Our results confirm that OBV/PTV/r +/- DSV +/- RBV is effective and generally well tolerated in a representative sample of the HCV monoinfected and HCV/HIV coinfected population in Spain within the experience of a national strategic plan to tackle HCV. FAU - Manuel Sousa, Jose AU - Manuel Sousa J AD - Hepatology Department, Hospital Universitario Virgen del Rocio, Sevilla, Sevilla, Spain. FAU - Vergara, Mercedes AU - Vergara M AD - Hepatology Unit, Digestive Disease Department, Parc Tauli Sabadell Hospital Universitari, Sabadell, Barcelona, Spain, CIBERehd, Instituto Carlos III, Madrid, Spain. FAU - Pulido, Federico AU - Pulido F AD - HIV Unit, Hospital Universitario 12 de Octubre, imas12, Universidad Complutense de Madrid (UCM), Madrid, Spain. FAU - Sanchez Antolin, Gloria AU - Sanchez Antolin G AD - Hepatology Department, Hospital Universitario Rio Hortega, Valladolid, Valladolid, Spain. FAU - Hijona, Lander AU - Hijona L AD - Hepatology Department, Hospital Universitario Araba, Vitoria-Gasteiz, Alava, Spain. FAU - Carnicer, Fernando AU - Carnicer F AD - Hepatology Department, Hospital General Universitario de Alicante, Alicante, Alicante, Spain. FAU - Rincon, Diego AU - Rincon D AD - Hepatology Department, Hospital General Universitario Gregorio Maranon, CIBERehd and (UCM), Madrid, Spain. FAU - Salmeron, Javier AU - Salmeron J AD - Hepatology Department, Complejo Hospitalario Universitario de Granada, Granada, Granada, Spain. FAU - Mateos-Munoz, Beatriz AU - Mateos-Munoz B AD - Hepatology Department, Hospital Universitario Ramon y Cajal, Madrid, Spain. FAU - Jou, Antoni AU - Jou A AD - HIV Clinical Unit, Internal Medicine Department and Fundacio de la Lluita contra la SIDA, Hospital Universitari Germans Trias i Pujol, Universitat Autonoma de Barcelona, Barcelona, Spain. FAU - Polo-Lorduy, Benjamin AU - Polo-Lorduy B AD - Hepatology Department, Hospital Universitario Fundacion Jimenez Diaz, Madrid, Spain. FAU - Rubin, Angel AU - Rubin A AD - Hepatology Department, Hospital Universitario y Politecnico de La Fe, Valencia, Valencia, Spain. FAU - Escarda, Ana AU - Escarda A AD - Hepatology Department, Hospital Universitario Son Espases, Palma de Mallorca, Spain. FAU - Aguilar, Patricia AU - Aguilar P AD - Digestive System Clinical Unit, Instituto Maimonides de Investigacion Biomedica de Cordoba (IMIBIC), Hospital Universitario Reina Sofia/Cordoba University, Cordoba, Spain. FAU - Aldamiz-Echevarria, Teresa AU - Aldamiz-Echevarria T AD - Infectious Diseases-HIV, Hospital General Universitario Gregorio Maranon (IiSGM), Madrid, Madrid, Spain. FAU - Garcia-Buey, Luisa AU - Garcia-Buey L AD - Hepatology Department, Hospital Universitario de La Princesa, Madrid, Spain. FAU - Carrion, Jose A AU - Carrion JA AUID- ORCID: 0000-0001-7191-6081 AD - Liver Section, Gastroenterology Department, Hospital del Mar, IMIM (Hospital del Mar Medical Research Institute), UAB (Universitat Autonoma de Barcelona) Barcelona, Spain. FAU - Hernandez-Guerra, Manuel AU - Hernandez-Guerra M AD - Hepatology Department, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain. FAU - Chimeno-Hernandez, Sonia AU - Chimeno-Hernandez S AD - Hepatology Department, Hospital Arnau de Vilanova, Valencia, Valencia, Spain. FAU - Espinosa, Nuria AU - Espinosa N AD - Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Infectious Diseases Research Group, Institute of Biomedicine of Seville (IBiS), University of Seville/CSIC,Sevilla, Spain. FAU - Morillas, Rosa M feminine AU - Morillas RM AUID- ORCID: 0000-0001-9117-5049 AD - Liver Section, Department of Gastroenterology, Hospital Universitari Germans Trias i Pujol, IGTP, Badalona, Barcelona, Spain, and CIBEREHD. FAU - Andrade, Raul J AU - Andrade RJ AD - Unidad de Gestion Clinica de Aparato Digestivo, Instituto de Investigacion Biomedica de Malaga-IBIMA, Hospital Universitario Virgen de la Victoria, Universidad de Malaga, Centro de Investigacion Biomedica en Red de Enfermedades Hepaticas y Digestivas CIBERehd, Malaga, Spain. FAU - Delgado, Manuel AU - Delgado M AD - Hepatology Department, Complejo Hospitalario Universitario A Coruna, A Coruna, Spain. FAU - Gallego, Adolfo AU - Gallego A AD - Hepatology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Barcelona, Spain. FAU - Magaz, Marta AU - Magaz M AD - Hepatology Department, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain. FAU - Moreno-Planas, Jose Maria AU - Moreno-Planas JM AD - Digestive System Department, Complejo Hospitalario Universitario de Albacete, Albacete, Spain. FAU - Estebanez, Angel AU - Estebanez A AD - Hepatology Department, Hospital Universitario Marques de Valdecilla, Santander, Cantabria, Spain. FAU - Rico, Mikel AU - Rico M AD - Infectious Diseases Unit, Hospital Universitario La Paz, Madrid, Spain. FAU - Menendez, Fernando AU - Menendez F AD - Hepatology Department, Hospital Universitario Basurto, Bilbao, Vizcaya, Spain. FAU - Sampedro, Blanca AU - Sampedro B AD - Hepatology Department, Hospital Galdakao, Galdakao, Vizcaya, Spain. FAU - Morano, Luis AU - Morano L AUID- ORCID: 0000-0002-0560-3260 AD - Infectious Diseases Unit, Hospital Universitario Alvaro Cunqueiro, Vigo, Pontevedra, Spain. FAU - Izquierdo, Sonia AU - Izquierdo S AD - Hepatology Department, Hospital Clinico San Carlos, Madrid, Spain. FAU - Zozaya, Jose Manuel AU - Zozaya JM AD - Hepatology Department, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain. FAU - Rodriguez, Manuel AU - Rodriguez M AD - Liver Unit, Division of Gastroenterology & Hepatology. Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain. FAU - Moran-Sanchez, Senador AU - Moran-Sanchez S AD - Hepatology Department, Hospital General Universitario Santa Lucia, Cartagena, Murcia, Spain. FAU - Lorente, Sara AU - Lorente S AD - Hepatology Department, Hospital Clinico Universitario Lozano Blesa, Zaragoza, Zaragoza, Spain. FAU - Martin-Granizo, Ignacio AU - Martin-Granizo I AD - Department of Gastroenterology, Hospital Universitario Alvaro Cunqueiro, Vigo, Pontevedra, Spain. FAU - Von-Wichmann, Miguel Angel AU - Von-Wichmann MA AD - Infectious Diseases Unit, Hospital Universitario Donostia, Donostia, Gipuzkoa, Spain. FAU - Delgado, Marcial AU - Delgado M AD - Infectious Diseases Unit, Hospital Regional Universitario de Malaga, Malaga, Spain. FAU - Manzanares, Amanda AU - Manzanares A AUID- ORCID: 0000-0003-1536-3560 AD - AbbVie Spain, S.L.U., Madrid, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191112 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Anilides) RN - 0 (Antiviral Agents) RN - 0 (Carbamates) RN - 0 (Cyclopropanes) RN - 0 (Lactams, Macrocyclic) RN - 0 (Macrocyclic Compounds) RN - 0 (Sulfonamides) RN - 2302768XJ8 (ombitasvir) RN - 49717AWG6K (Ribavirin) RN - 56HH86ZVCT (Uracil) RN - 9DLQ4CIU6V (Proline) RN - CKR7XL41N4 (2-Naphthylamine) RN - DE54EQW8T1 (dasabuvir) RN - HG18B9YRS7 (Valine) RN - OU2YM37K86 (paritaprevir) SB - IM MH - 2-Naphthylamine MH - Anilides/adverse effects/therapeutic use MH - Antiviral Agents/adverse effects/*therapeutic use MH - Carbamates/adverse effects/therapeutic use MH - Cyclopropanes MH - Drug Therapy, Combination MH - Female MH - Follow-Up Studies MH - HIV Infections/*drug therapy MH - HIV-1/genetics MH - Hepatitis C, Chronic/*drug therapy MH - Humans MH - Lactams, Macrocyclic MH - Logistic Models MH - Macrocyclic Compounds/adverse effects/therapeutic use MH - Male MH - Middle Aged MH - Multivariate Analysis MH - Proline/analogs & derivatives MH - Ribavirin/adverse effects/therapeutic use MH - Spain MH - Sulfonamides/adverse effects/therapeutic use MH - Sustained Virologic Response MH - Treatment Outcome MH - Uracil/adverse effects/analogs & derivatives/therapeutic use MH - Valine PMC - PMC6850697 COIS- Jose Manuel Sousa has received fees as speaker from AbbVie, MSD and Gilead. Mercedes Vergara has received fees as an advisory board member from Gilead and has given lectures for AbbVie, Intercept, MSD, Janssen-Cilag and Gilead. Federico Pulido has received fees as speaker and advisor from AbbVie, Gilead, Janssen and MSD. Gloria Sanchez-Antolin has acted as speaker for AbbVie, MSD, Gilead Science, Novartis and Astellas. Diego Rincon has given lectures for AbbVie and MSD. Javier Salmeron has received speaker fees and grant funding from AbbVie; he declares no further conflict of interest. Luisa Garcia-Buey has received speaker fees and travel grants from Abbvie, MSD and Gilead. Jose A. Carrion has received speaker fees from Abbvie, Gilead and MSD and has received fees as Advisor for AbbVie. Manuel Hernandez-Guerra has been a consultant to Gilead Sciences, Intercept Pharmaceuticals, Abbvie and Bayer; he has received grant funding from Gilead Sciences and Abbvie. Nuria Espinosa has participated in Clinical Trials managed by Gilead and ViiV Healthcare; she has received advisory board, conference and course fees as well as expenses for attending congresses from Janssen-Cilag, Gilead Sciences, ViiV Healthcare, MSD and Abbvie. Rosa M feminine Morillas has acted as a speaker for Gilead, Merck, AbbVie and Intercept, and has participated in advisory boards for AbbVie, Gilead and Intercept. Raul J. Andrade: Advisor/Speaker Bureau: Abbvie, Gilead Sciences, Merck Sharp and Dohme, Bristol-Myers Squibb, Janssen; Research Grants: Willmar Schwabe GmbH & Co, Gedeon Richter/Preglem S.A. Manuel Delgado has received scientific advisor fees from Abbie, Gilead, MSD. Jose M Moreno-Planas has received speaker fees from AbbVie, MSD, Gilead and Bayer. Fernando Menendez has received fees as advisor from Bayer. Luis Morano has acted as speaker, advisor and/or investigator for Abbvie, Gilead Sciences, Merck Sharp and Dohme, Bristol-Myers Squibb, Janssen, Boehringer Ingelheim, Novartis, and Roche Farma. Manuel Rodriguez consults for and is on the speaker's bureau for Gilead and AbbVie. Sara Lorente has received lecture fees from Abbvie, Gilead Sciences and MSD. Miguel Angel Von-Wichmann has received fees as speaker and advisor from Abbvie, BMS, Gilead, Janssen, MSD and VIIV. Amanda Manzanares is employee of AbbVie and may hold stock or options. Lander Hijona, Fernando Carnicer, Beatriz Mateos-Munoz, Antoni Jou, Benjamin Polo-Lorduy, Angel Rubin, Ana Escarda, Patricia Aguilar, Teresa Aldamiz-Echevarria, Sonia Chimeno-Hernandez, Adolfo Gallego, Marta Magaz, Angel Estebanez, Mikel Rico, Blanca Sampedro, Sonia Izquierdo, Jose Manuel Zozaya, Senador Moran-Sanchez, Ignacio Martin-Granizo, Marcial Delgado declare no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. EDAT- 2019/11/13 06:00 MHDA- 2020/03/21 06:00 PMCR- 2019/11/12 CRDT- 2019/11/13 06:00 PHST- 2019/07/24 00:00 [received] PHST- 2019/10/27 00:00 [accepted] PHST- 2019/11/13 06:00 [entrez] PHST- 2019/11/13 06:00 [pubmed] PHST- 2020/03/21 06:00 [medline] PHST- 2019/11/12 00:00 [pmc-release] AID - PONE-D-19-20903 [pii] AID - 10.1371/journal.pone.0225061 [doi] PST - epublish SO - PLoS One. 2019 Nov 12;14(11):e0225061. doi: 10.1371/journal.pone.0225061. eCollection 2019.