Efficacy and Safety of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir ± Ribavirin for HCV in Brazilian Adults with Advanced Fibrosis.

Abstract

INTRODUCTION AND AIM:

Approximately 650,000 people in Brazil have chronic hepatitis C virus (HCV) infection. We evaluated the safety and efficacy of ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus dasabuvir (DSV) with/without ribavirin (RBV) in an openlabel multicenter phase 3b trial in treatment-naive or interferon (IFN) treatment-experienced Brazilian patients with advanced hepatic fibrosis (METAVIR F3/4) and HCV genotype (GT) 1 infection.

MATERIAL AND METHODS:

All patients received coformulated OBV/PTV/r daily + DSV twice daily (3-DAA). GT1a-infected patients received 3-DAA plus RBV for 12 weeks, except for prior pegIFN/RBV nonresponders with cirrhosis who were treated for 24 weeks. GT1b-infected patients received 3-DAA alone (F3) or in combination with RBV (F4) for 12 weeks. The primary endpoint was sustained virologic response (HCV RNA < 15 IU/mL) at post-treatment Week 12 (SVR12).

RESULTS:

The study enrolled 222 patients, 214 achieved an SVR12 (96.4%; 95% CI, 93.1-98.2%), one GT1a-infected patient experienced virologic breakthrough, six (5 GT1a) relapsed, and one was lost to follow-up. SVR12 was achieved in 111/ 112 (99.1%) GT1b-infected patients, including 42/43 (97.7%) noncirrhotic, and 69/69 (100%) cirrhotic patients; and in 103/110 (93.6%) GT1a-infected patients, including 44/46 (95.7%) noncirrhotic and 59/64 (92.2%) cirrhotic patients. Overall there was a low rate of serious adverse events (n = 6, 2.7%). One patient experienced a treatment-related serious adverse event and one patient discontinued treatment because of an adverse event.

DISCUSSION:

The results confirm that the 3-DAA regimen with/without RBV is well tolerated and had a favorable safety profile and is efficacious in GT1-infected patients with advanced fibrosis (METAVIR F3/4).

• Authors: Mario G Pessoa, José V Ramalho-Madruga, Katia Alves, Estevão P Nunes, Hugo Cheinquer, Carlos E Brandão-Mello, Maria C Mendes-Correa, Maria L Ferraz, Paulo R A Ferreira, Mário R Álvares-da-Silva, Henrique S Coelho, Evaldo S Affonso-de-Araújo, Juvencio Furtado, Raymundo Parana, Giovanni Silva, Sara A Lari, Li Liu, Rakesh Tripathi, Tami Pilot-Matias, Daniel E Cohen, Nancy S Shulman, Ana Martinelli
• Journal: Annals of hepatology (Ann Hepatol) Vol. 17 Issue 6 Pg. 959-968 (Oct 16 2018) ISSN: 1665-2681 [Print] Mexico
• PMID: 30600291 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study)

Chemical References

• Anilides
• Antiviral Agents
• Carbamates
• Cyclopropanes
• Drug Combinations
• Lactams, Macrocyclic
• Macrocyclic Compounds
• RNA, Viral
• Sulfonamides
• ombitasvir
• Ribavirin
• Uracil
• Proline
• 2-Naphthylamine
• dasabuvir
• Valine
• Ritonavir
• paritaprevir

Topics

• 2-Naphthylamine
• Adult
• Aged
• Anilides (administration & dosage, adverse effects)
• Antiviral Agents (administration & dosage, adverse effects)
• Brazil
• Carbamates (administration & dosage, adverse effects)
• Cyclopropanes
• Drug Combinations
• Drug Resistance, Viral
• Drug Therapy, Combination
• Female
• Genotype
• Hepacivirus (drug effects, genetics)
• Hepatitis C, Chronic (diagnosis, drug therapy, virology)
• Humans
• Lactams, Macrocyclic
• Liver Cirrhosis (diagnosis, drug therapy, virology)
• Macrocyclic Compounds (administration & dosage, adverse effects)
• Male
• Middle Aged
• Proline (analogs & derivatives)
• RNA, Viral (blood, genetics)
• Ribavirin (administration & dosage, adverse effects)
• Ritonavir (administration & dosage, adverse effects)
• Sulfonamides (administration & dosage, adverse effects)
• Sustained Virologic Response
• Time Factors
• Treatment Outcome
• Uracil (administration & dosage, adverse effects, analogs & derivatives)
• Valine
• Viral Load