All patients had a follow-up (FU) visit 24 weeks after the end of treatment. Rapamycin Sirolimus Figure 1 Design of the study. Patients were evaluated as outpatients for safety, tolerance, and efficacy at the start of the therapy (d-7 of group A; d0 of group B), at 24 h (d1), 48 h (d2), 96 h (d4) and 144 h (d7) after the first injection of pegIFN��2b. Further evaluations during the combination therapy were at weeks 2 (w2), w4, w8, w12, w24 and w48, and at FU (w72) 24 weeks after the end of treatment (Figure 1). HCV RNA was quantified with the COBAS? AmpliPrep Taqman HCV-Test from Roche Molecular Systems according to the manufacturer’s instructions. HCV genotyping was performed by reverse hybridization (Inno Lipa HCV, Innogenetics, Gent, Belgium).

Histopathological grading and staging of the HCV liver biopsies according to the Metavir classification system was performed at the Pathology Institute of the University Hospital Basel. Adverse events were documented throughout the study duration. Ethics Statement The study was approved by the ethics committee of the Kanton Basel and by Swissmedic and was carried out according to the Declaration of Helsinki and the International Conference on Harmonisation/Committee for Proprietary Medicinal Products (ICH/CPMP) guidelines ��Good Clinical Practice��. All patients gave written informed consent before enrollment. The study conduct was monitored by KMS Kammermann Monitoring Services GmbH, Zug, Switzerland. The study was registered at ClinicalTrials.gov under the registration number NCT00310336.

Results Characteristics of the Patients 25 male and 8 female patients between 30 and 64 years of age, all Caucasians, were screened and enrolled in the study from October 2006 to April 2008. All patients had been previously treated in the hepatology outpatient clinic of the University Hospital of Basel. 16 patients were randomized into group A, and 17 into group B (see Figure 1). The randomization was performed in two separate groups for GTs 1/4 and for GTs 2/3. 2 male patients, both randomized into group A, withdrew their consent before the first application of study medication. One male patient from group A discontinued treatment after 4 days, and another male patient from group B withdrew from the study 2 weeks after treatment initiation.

The remaining 29 patients were treated according to the protocol with the exception of two patients (#18 and #20) who received a liver transplant after 5 and 9 months of therapy AV-951 because of development of hepatocellular carcinoma. The baseline characteristics of the 29 study patients are shown in Table 1. 23 patients were infected with HCV GT1 (79%), and 2 each with GT2 (7%), GT3 (7%) and GT4 (7%). The mean VL was 6.24 log10 IU/ml. 21 patients (72%) had advanced fibrosis (Metavir stages 3 or 4), 16 patients (55%) were cirrhotic.