title: Ultrasensitive HCV RNA Quantification in Antiviral Triple Therapy: New Insight on Viral Clearance Dynamics and Treatment Outcome Predictors.
abstract: OBJECTIVE
  Identifying the predictive factors of Sustained Virological Response (SVR) represents an important challenge in new interferon-based DAA therapies. Here, we analyzed the kinetics of antiviral response associated with a triple drug regimen, and the association between negative residual viral load at different time points during treatment.
  
  
  METHODS
  Twenty-three HCV genotype 1 (GT 1a n = 11; GT1b n = 12) infected patients were included in the study. Linear Discriminant Analysis (LDA) was used to establish possible association between HCV RNA values at days 1 and 4 from start of therapy and SVR. Principal component analysis (PCA) was applied to analyze the correlation between HCV RNA slope and SVR. A ultrasensitive (US) method was established to measure the residual HCV viral load in those samples which resulted "detected <12IU/ml" or undetectable with ABBOTT standard assay, and was retrospectively used on samples collected at different time points to establish its predictive power for SVR.
  
  
  RESULTS
  According to LDA, there was no association between SVR and viral kinetics neither at time points earlier than 1 week (days 1 and 4) after therapy initiation nor later. The slopes were not relevant for classifying patients as SVR or no-SVR. No significant differences were observed in the median HCV RNA values at T0 among SVR and no-SVR patients. HCV RNA values with US protocol (LOD 1.2 IU/ml) after 1 month of therapy were considered; the area under the ROC curve was 0.70. Overall, PPV and NPV of undetectable HCV RNA with the US method for SVR was 100% and 46.7%, respectively; sensitivity and specificity were 38.4% and 100% respectively.
  
  
  CONCLUSIONS
  HCV RNA "not detected" by the US method after 1 month of treatment is predictive of SVR in first generation Protease inhibitor (PI)-based triple therapy. The US method could have clinical utility for advanced monitoring of virological response in new interferon based DAA combination regimens.
authors: Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
authors: Anna Rosa
authors: AR
authors: Garbuglia
authors: Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
authors: Ubaldo
authors: U
authors: Visco-Comandini
authors: Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
authors: Raffaella
authors: R
authors: Lionetti
authors: Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
authors: Daniele
authors: D
authors: Lapa
authors: Istituto per le Applicazioni del Calcolo (IAC)-CNR, Rome, Italy.
authors: Filippo
authors: F
authors: Castiglione
authors: Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
authors: Gianpiero
authors: G
authors: D'Offizi
authors: Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
authors: Chiara
authors: C
authors: Taibi
authors: Clinical Department, "Lazzaro Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
authors: Marzia
authors: M
authors: Montalbano
authors: Laboratory of Virology, "Lazzaro Spallanzani" National Institute for Infectious Diseases, IRCCS, Rome, Italy.
authors: Maria Rosaria
authors: MR
authors: Capobianchi
authors: Istituto di Analisi dei Sistemi ed Informatica "Antonio Ruberti" (IASI)-CNR, Rome, Italy.
authors: Paola
authors: P
authors: Paci
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry; D025341:Principal Component Analysis; D012367:RNA, Viral / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012254:Ribavirin / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D009842:Oligopeptides; D012367:RNA, Viral; D011092:Polyethylene Glycols; D012254:Ribavirin; C486464:telaprevir