Rapid prediction of sustained virological response in patients chronically infected with HCV by evaluation of RNA decay 48h after the start of treatment with pegylated interferon and ribavirin.
The combination of pegylated interferons (PEG-IFNs) and ribavirin represents the standard of care for the treatment of chronic HCV-infected patients, yet with a success rate around 50% in genotypes 1 and 4, high costs and side effects. Therefore, early prediction of sustained virological response (SVR) is a relevant issue for HCV-patients. We evaluated the association between SVR and decline of HCV-RNA at 48h in a prospective cohort of 145 HCV-patients treated with PEG-IFNs and ribavirin (males=69.1%; genotypes 1/4=51.0%; HIV-1 coinfected=6.7%). SVR was obtained in 65.5% of patients, while 16.6% experienced relapse and 17.9% no response. The first-phase of HCV-RNA decline clearly differentiated patients with SVR from relapsers and non-responders, independently of genotype (P<0.001). In univariate and multivariate analyses, different infralogaritmic thresholds of HCV-RNA decay at 48h were tested, observing the highest predictive potential at 0.5log: decays above this threshold showed a 76.2% negative predictive value for SVR, whereas decays >0.5log indicated a 6.8 odds ratio (95% C.I.: 2.0-23.2) for SVR after controlling for genotype, baseline viremia, adherence to therapy and HIV coinfection. Decays beyond the 0.5log threshold were also strongly associated with and highly predictive of early virological response (95.0% positive predictive value, P<0.001).
Parruti
Giustino
G
Infectious Disease Unit, Pescara General Hospital, Via Fonte Romana, 8 - 65124 Pescara, Italy. parruti@tin.it
Polilli
Ennio
E
Sozio
Federica
F
Cento
Valeria
V
Pieri
Alessandro
A
Di Masi
Francesco
F
Mercurio
Fabio
F
Tontodonati
Monica
M
Mazzotta
Elena
E
Ceccherini-Silberstein
Francesca
F
Manzoli
Lamberto
L
Perno
Carlo Federico
CF
D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications; D016174:Hepacivirus; D006526:Hepatitis C / Q000188:drug therapy; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D020871:RNA Stability; D012367:RNA, Viral / Q000378:metabolism*; D011994:Recombinant Proteins; D012008:Recurrence; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
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