title: 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.
abstract: 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).
authors: Infectious Disease Unit, Pescara General Hospital, Via Fonte Romana, 8 - 65124 Pescara, Italy. parruti@tin.it
authors: Giustino
authors: G
authors: Parruti
authors: Ennio
authors: E
authors: Polilli
authors: Federica
authors: F
authors: Sozio
authors: Valeria
authors: V
authors: Cento
authors: Alessandro
authors: A
authors: Pieri
authors: Francesco
authors: F
authors: Di Masi
authors: Fabio
authors: F
authors: Mercurio
authors: Monica
authors: M
authors: Tontodonati
authors: Elena
authors: E
authors: Mazzotta
authors: Francesca
authors: F
authors: Ceccherini-Silberstein
authors: Lamberto
authors: L
authors: Manzoli
authors: Carlo Federico
authors: CF
authors: Perno
mesh_terms: 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
chemical_list: 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