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Dig Liver Dis. 2015 Feb;47(2):157-63. doi: 10.1016/j.dld.2014.11.010. Epub 2014 Nov 24.

Hepatitis C virus RNA levels at week-2 of telaprevir/boceprevir administration are predictive of virological outcome.

Author information

1
Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy.
2
Hepatology Unit, University Hospital of Rome "Tor Vergata", Rome, Italy.
3
Unit of Microbiology, Hospital Sacco of Milan, Milan, Italy.
4
Infectious Disease Clinic, Chieti, Italy; Infectious Disease Unit, Pescara General Hospital, Pescara, Italy.
5
Infectious Diseases Unit, Department of Clinical and Experimental Medicine, University of Sassari, Italy.
6
"La Sapienza" University, Rome, Italy.
7
S. Martino Hospital, Genova, Italy.
8
Hepatology Unit, National Institute of Health, Migration and Poverty, Rome, Italy.
9
Infectious Disease, University Hospital of Rome "Tor Vergata", Rome, Italy.
10
Gastroenterology, Catholic University of Rome, Rome, Italy.
11
Division of Infectious Disease, Hospital Sacco of Milan, Milan, Italy.
12
Hepatology Unit, San Camillo Forlanini Hospital, Rome, Italy.
13
Infectious Disease Clinic, Chieti, Italy.
14
Infectious Disease Unit, Pescara General Hospital, Pescara, Italy.
15
Department of Experimental Medicine and Surgery, University of Rome "Tor Vergata", Rome, Italy. Electronic address: ceccherini@med.uniroma2.it.

Abstract

BACKGROUND:

Triple therapy with telaprevir/boceprevir + pegylated-interferon+ribavirin can achieve excellent antiviral efficacy, but it can be burdened with resistance development at failure.

AIMS:

To evaluate kinetics of hepatitis C virus (HCV) RNA decay and early resistance development, in order to promptly identify patients at highest risk of failure to first generation protease inhibitors.

METHODS:

HCV-RNA was prospectively quantified in 158 patients receiving pegylated-interferon+ribavirin+telaprevir (N = 114) or+boceprevir (N = 44), at early time-points and during per protocol follow-up. Drug resistance was contextually evaluated by population sequencing.

RESULTS:

HCV-RNA at week-2 was significantly higher in patients experiencing virological failure to triple-therapy than in patients with sustained viral response (2.3 [1.9-2.8] versus 1.2 [0.3-1.7]log IU/mL, p < 0.001). A 100 IU/mL cut-off value for week-2 HCV-RNA had the highest sensitivity (86%) in predicting virological success. Indeed, 23/23 (100%) patients with undetectable HCV-RNA reached success, versus 26/34 (76.5%) patients with HCV-RNA<100 IU/mL, and only 11/31 (35.5%) with HCV-RNA > 100 IU/mL (p < 0.001). Furthermore, differently from failing patients, none of the patient with undetectable HCV-RNA at week-2 had baseline/early resistance.

CONCLUSIONS:

With triple therapy based on first generation protease inhibitors, suboptimal HCV-RNA decay at week-2 combined with early detection of resistance can help identifying patients with higher risk of virological failure, thus requiring a closer monitoring during therapy.

KEYWORDS:

Early response; NS3 protease inhibitors; Viral kinetics; Virological failure

PMID:
25544656
DOI:
10.1016/j.dld.2014.11.010
[Indexed for MEDLINE]

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