title: Relationship between the early boceprevir-S isomer plasma concentrations and the onset of breakthrough during HCV genotype 1 triple therapy.
abstract: In a prospective cohort of 18 patients treated with boceprevir, we examined the role of boceprevir plasma concentration at the onset of breakthrough during the treatment. Nine patients experienced breakthrough during therapy. The resistance patterns were as follows: S122S/R, I132V, T54A/I132V, V156S/I170A, V36M/T54S/R155K, V36M/R155K and T54/R155K. Boceprevir-S isomer (SCH 534128) median concentration in patients with breakthrough was 48.3 ng/mL (interquartile range 43-58 ng/mL); in others, it was significantly (p 0.019) higher: 151 ng/mL. Low boceprevir plasma concentration can lead to virologic resistance; therapeutic drug monitoring should be used to prevent the onset of viral breakthrough during triple-regimen therapy with boceprevir.
authors: Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy. Electronic address: lucio.boglione@unito.it.
authors: L
authors: L
authors: Boglione
authors: Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
authors: A
authors: A
authors: De Nicolò
authors: Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
authors: C S
authors: CS
authors: Cardellino
authors: Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
authors: T
authors: T
authors: Ruggiero
authors: Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
authors: V
authors: V
authors: Ghisetti
authors: Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
authors: G
authors: G
authors: Cariti
authors: Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
authors: G
authors: G
authors: Di Perri
authors: Department of Infectious Diseases, University of Turin, Amedeo di Savoia Hospital, Turin, Italy.
authors: A
authors: A
authors: D'Avolio
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D015331:Cohort Studies; D016903:Drug Monitoring; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010949:Plasma / Q000737:chemistry*; D011392:Proline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011446:Prospective Studies; D012254:Ribavirin / Q000008:administration & dosage; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D011392:Proline
keywords: Boceprevir; HCV; breakthrough; resistance; triple therapy