Effectiveness of first-wave protease inhibitors in hepatitis C virus genotype 1 infection: a multicenter study in Brazil

Lobato, Cirley Maria de Oliveira; Balassiano, Natalia; Hyppolito, Elodie Bomfim; Sanchez-Lermen, Rafaela Liz Pellegrim; Signorelli, Izabelle Venturini; Nicacio, Miguel Yasuo Tomita; Firmino Filho, Alberto Pereira; Andrade, Thais Guaraná de; Lima, José Milton de Castro; Arruda, Talita Amorim de; Coutinho, Fernanda Schwanz; Araujo, Everton Felipe do Vale; Esmeraldo, Ticiana Mota; Cortez, Erlon; Capeli, Rafaela Lorenzon Aragão; Matos, Melquior Brunno Mateus de; Pessoa, Francisco Sérgio Rangel; Oliveira, Hélder Cássio de; Arruda, Érico Antônio Gomes de; Gonçalves, Patrícia Lofêgo; Araújo Filho, Antônio Haroldo; Esberard, Eliane Bordalo Cathalá; Souto, Francisco José Dutra

Abstract INTRODUCTION:

In 2013, combination therapy using peginterferon, ribavirin, and boceprevir or telaprevir was introduced to treat hepatitis C virus genotype 1 infection in Brazil. The effectiveness of this therapy in four Brazilian regions was evaluated.

METHODS:

Clinical and virological data were obtained from patients of public health institutions in five cities, including sustained virological response (SVR) and side effects. Patients with advanced fibrosis (F3/4), moderate fibrosis (F2) for > 3 years, or extra-hepatic manifestations were treated according to Ministry of Health protocol. Treatment effectiveness was verified by using bivariate and multivariate analysis; p-values of < 0.05 were considered significant.

RESULTS:

Of 275 patients (64.7% men; average age, 57 years old), most (61.8%) were treatment-experienced; 53.9% had subgenotype 1a infection, 85.1% had advanced fibrosis, and 85.5% were treated with telaprevir. SVR was observed in 54.2%. Rapid virological response (RVR) was observed in 54.6% of patients (data available for 251 patients). Overall, 87.5% reported side effects and 42.5% did not complete treatment. Skin rash, severe infection, and death occurred in 17.8%, 2.5%, and death in 1.4% of cases, respectively. SVR was associated with treatment completion, RVR, and anemia.

CONCLUSIONS:

The effectiveness of hepatitis C virus triple therapy was lower than that reported in phase III clinical trials, possibly owing to the prioritized treatment of patients with advanced liver fibrosis. The high frequency of side effects and treatment interruptions observed supported the decision of the Brazilian authorities to suspend its use when safer and more effective drugs became available in 2015.