Role of telaprevir plasma levels for predicting response to antiviral therapy in patients with hepatitis C virus genotype 1 infection.
OBJECTIVE
Telaprevir (TVR)-based triple therapy has substantially improved cure rates of hepatitis C virus (HCV) genotype 1 infection but side effects are frequent and often severe. Therefore, response predictors are needed for early identification of patients not responding to TVR-based triple therapy.


METHODS
Forty-five patients (mean age: 54 ± 13 years; male gender: 60%; treatment-experienced: 82%; cirrhosis: 58%) with HCV genotype 1 infection were treated with a TVR-based triple-therapy regimen. TVR plasma levels were analyzed by liquid chromatography electrospray-ionization-tandem mass spectrometry at weeks 2, 4, 8, and 12 of antiviral therapy. On-treatment HCV RNA response was assessed at weeks 4, 12, and 24 by real-time polymerase chain reaction.


RESULTS
An extended rapid virological response (eRVR) and sustained virological response (SVR) was achieved in 21 of 45 patients (47%) and 36 of 45 (80%) patients, respectively. Mean ± standard deviation TVR plasma levels at week 2 were 3.4 ± 0.2 log10 ng/ml and did not differ over time (when assessed at weeks 4, 8, and 12). TVR plasma levels at week 2 were significantly higher in patients who achieved an eRVR compared to those who did not achieve eRVR (3.5 ± 0.1 vs. 3.3 ± 0.2 log10 ng/ml; p = 0.003) but were neither associated with SVR nor with treatment-related anemia.


CONCLUSIONS
TVR plasma levels are associated with on-treatment response but not with overall treatment efficacy. Given the high overall response rates to TVR-based triple therapy, our data suggest that TVR trough levels may not be a useful predictor of treatment response, and routine drug-level monitoring is not required.
Medizinische Klinik 1, Universitätsklinikum Frankfurt , Theodor-Stern-Kai 7, 60590 Frankfurt am Main , Germany.
Harald
H
Farnik
Nerea
N
Ferreirós
Sandra
S
Labocha
Gerd
G
Geisslinger
Stefan
S
Zeuzem
Christoph
C
Sarrazin
Johannes
J
Vermehren
D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C486464:telaprevir; C100416:peginterferon alfa-2a
drug monitoring, hepatitis C virus; plasma levels; telaprevir