Antiviral Therapy 10:309–317
Open, randomized, multicentre Italian trial on PEGIFN plus ribavirin versus PEG-IFN monotherapy for chronic hepatitis C in HIV-coinfected patients on HAART Antonietta Cargnel 1*, Elena Angeli1, Annalisa Mainini1, Guido Gubertini1, Riccardo Giorgi1, Monica Schiavini1, Piergiorgio Duca 2 and the Italian Co-infection Study (ICOS) Group 1 2
II Department Infectious Diseases, Luigi Sacco Hospital, Milan, Italy Statistics Department, University of Milan, Milan, Italy
*Corresponding author: Tel: +39 02 3904 2379; Fax: +39 02 3820 0909; E-mail:
[email protected],
[email protected]
Background: Chronic hepatitis C is common and aggressive in HIV-positive patients, so the development of a well-tolerated HCV therapy is a priority. We evaluated the efficacy and safety of pegylated interferon α2b (PEGIFN) plus ribavirin (RBV) versus PEG-IFN monotherapy in HIV/HCV-coinfected patients undergoing highly active antiretroviral therapy (HAART), and analysed the predictive factors of response. Methods: An Italian, multicentre, open-label trial including 135 coinfected patients, randomized to PEGIFN 1.5 µg/kg/week plus RBV 400 mg twice daily (n=69, arm A) or PEG-IFN 1.5 µg/kg/week (n=66, arm B) for 48 weeks. We assessed the predictive values of early virological response (EVR) at week 8 (HCV-RNA drop >2 log10 compared with baseline or undetectable levels) on sustained virological response (SVR). Results: Fifty-five patients (28 from arm A and 27 from arm B) completed 48 weeks of therapy. At the end of treatment, 20/28 patients in arm A and 11/27 in arm B had HCV-RNA 100 000/mm3. Exclusion criteria were: previous treatment with IFN, PEG-IFN alone or in combination with RBV; treatment for chronic hepatitis with another antiviral or immunomodulator in the previous 2 years; presence of other causes of liver disease, excluding chronic HCV infection; advanced/decompensated liver disease; presence of serious disease of the central nervous system, cardiovascular system, respiratory tract or retina; haemophilia or other forms of haemoglobinopathy, decompensated diabetes, severe psychiatric disorders, immunomediated diseases or diseases requiring chronic steroid treatment; and drug addiction or alcohol ingestion ≥80 g/day and/or methadone therapy during the last 2 years.
Assessment of efficacy Efficacy of the two different treatments was compared using (i) end-of-treatment response (ETR): HCV-RNA [polymerase chain reaction (PCR)] negative at 48 weeks of therapy; (ii) sustained virological response (SVR): ETR and HCV-RNA (PCR) persistently negative 24 weeks after end of treatment; and (iii) no response (NR): HCV-RNA (PCR) positive at 48 weeks of therapy. Quantitative HCV-RNA was measured by a branched DNA signal amplification (Quantiplex HCV RNA v2.0; Chiron-Bayer, Emeryville, CA, USA) at baseline and at weeks 8, 24, 48 and 72. Qualitative HCV-RNA was performed through polymerase chain reaction assay (Cobas Amplicor HCV Monitor v2.0; Roche Diagnostics, Nutley, NJ, USA, with a sensitivity of 50 IU/ml) at weeks 8, 24, 48 and 72. HCV genotypes were determined at entry by reverse hybridization using the Inno-Lipa HCV (Innogenetics, Ghent, Belgium).
Assessment of safety Safety was evaluated by means of the World Health Organization toxicity scale. Haematochemical monitoring was performed monthly and included CD4+ cell counts. HIV-RNA plasma levels were determined at baseline and at weeks 24, 48 and 72 (by branched DNA; Chiron-Bayer, threshold 50 copies/ml). When haematological and biochemical toxicities occurred, dose reduction of PEG-IFN and RBV were applied. If the haemoglobin level fell to
