A simple rule to personalize standard dual therapy across all genotypes in naive chronic hepatitis C patients: the TT4 randomized trial.
BACKGROUND
Rapid and early virological responses to peginterferon-alpha and ribavirin are predictive of sustained virological response (SVR) in hepatitis C virus (HCV) infection. We aimed at finding a simple rule to determine the shortest duration of dual therapy for all HCV genotypes, obtained by multiplying time to Initial Viral Response, IVR (first undetectable HCV-RNA) by 4 (Tailored Therapy-4, or TT4).


METHODS
267 naïve HCV-infected patients with compensated liver disease were randomized (2:1) to the TT4 (n=180) or current standard-of-care (SoC, n=87) and received peginterferon-alpha plus ribavirin. Patients with HCV-RNA decrease ≤2log10 at week 12 or detectable HCV-RNA at week 24 discontinued treatment.


RESULTS
Both groups had comparable baseline characteristics, SVR rates were similar in the whole population (60.6% vs. 60.9%) and within each genotype subgroup (G1: 46.6% vs. 55.6%; G2: 90.2% vs. 94.4%; G3: 74.1% vs. 58.3%; G4: 45.8% vs. 33.3%). Relapse rate was higher in G1-TT4 than G1-SoC. Treatment duration in SVR patients was shorter in TT4 compared to SoC, both overall [25±15 vs. 36±12.1 weeks], and for subgroups: G1 [35.3±16.7 vs. 47.3±2.6 weeks], G2 [18.3±7.5 vs. 24±2.8 weeks], G3 [15.2±8.7 vs. 22.8±3 weeks] and G4 [26.9±13 vs. 48 weeks].


CONCLUSIONS
In HCV-naive patients, TT4-rule treatment yields similar SVR rates compared to SoC but with shorter treatment duration and remarkable cost reduction.
Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy. Electronic address: simona.francioso@uniroma2.it.
Simona
S
Francioso
Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.
Cristiana
C
Almerighi
G. Careggi Hospital, University of Florence, Italy.
Paolo
P
Forte
SS Annunziata Hospital, Sassari, Italy.
Franco
F
Bandiera
National Institute for Health Migration and Poverty (NIHMP), Rome, Italy.
Lorenzo
L
Nosotti
National Institute of Infectious Diseases, L. Spallanzani Hospital, Rome, Italy.
Raffaella
R
Lionetti
Department of Infectious and Tropical Diseases, Sapienza University, Rome, Italy.
Gloria
G
Taliani
G. Brotzu Hospital, Cagliari, Italy.
Maria Rosaria
MR
Piras
G. Brotzu Hospital, Cagliari, Italy.
Maria Laura
ML
Ponti
Ospedale Civile, Pescara, Italy.
Giustino
G
Parruti
S.M. Misericordia Hospital, Perugia, Italy.
Francesco
F
Di Candilo
Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.
Silvia
S
Gentile
Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.
Paola
P
Piccolo
Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.
Angela
A
Salso
Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.
Francesca
F
Riccobelli
G. Careggi Hospital, University of Florence, Italy.
Sara
S
Renzi
National Institute of Infectious Diseases, L. Spallanzani Hospital, Rome, Italy.
Maria Antonella
MA
Longo
National Institute of Infectious Diseases, L. Spallanzani Hospital, Rome, Italy.
Marzia
M
Montalbano
SS Annunziata Hospital, Sassari, Italy.
Salvatore
S
Zaru
Department of Infectious and Tropical Diseases, Sapienza University, Rome, Italy.
Elisa
E
Biliotti
Ospedale Civile, Pescara, Italy.
Francesco
F
Di Masi
Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.
Francesco
F
Santopaolo
Hepatology and Liver Transplantation Unit, Department of Experimental Medicine and Surgery, Tor Vergata University, Rome, Italy.
Mario
M
Angelico
D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D057285:Precision Medicine / Q000379:methods; D012367:RNA, Viral / Q000235:genetics*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a
Dual therapy; HCV treatment; Individualized therapy; Pegylated interferon; Rapid viral response; Response-guided therapy; Ribavirin