Impact of ribavirin exposure on early virological response to hepatitis ...

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Marina Núnez1, Nuria Camino1, Belén Ramos1, Miguel Angel Berdún2, Pablo Barreiro1, Elena Losada3, ..... Torriani F, Rodriguez-Torres M & Rockstroh J.
Antiviral Therapy 10:657–662

Impact of ribavirin exposure on early virological response to hepatitis C therapy in HIV-infected patients with chronic hepatitis C Marina Núnez1, Nuria Camino1, Belén Ramos1, Miguel Angel Berdún2, Pablo Barreiro1, Elena Losada3, Ignacio Santos4, Santiago Echevarría5, Antonio Ocampo6, Celia Miralles6, Piedad Arazo7, Luz MartínCarbonero1, Miriam Romero8, Javier García-Samaniego8 and Vincent Soriano1* 1

Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain Hospital San Jorge, Huesca, Spain 3 Hospital Universitario, Santiago de Compostela, Spain 4 Hospital La Princesa, Madrid, Spain 5 Hospital Marqués de Valdecilla, Santander, Spain 6 Hospital Xeral Cíes, Vigo, Spain 7 Hospital Miguel Servet, Zaragoza, Spain 8 Hepatology Unit, Hospital Carlos III, Madrid, Spain 2

*Corresponding author: Tel: +34 91 453 2500; Fax: +34 91 733 6614: E-mail: [email protected]

Background: The use of pegylated interferon (PEG-IFN) plus ribavirin (RBV) is currently the recommended treatment for chronic hepatitis C virus (HCV) infection. Coinfection with HIV is a negative predictor of response, for reasons not well understood. Methods: We examined the virological response at weeks 4 and 12 in 198 HCV/HIV-coinfected patients enrolled in a prospective trial in which PEG-IFN alpha 2a (180 µg per week) and RBV (1000-1200 mg daily) were provided. Results: In an on-treatment analysis, 52.8% of patients achieved undetectable HCV-RNA (2 log10 reductions in HCV-RNA at week 12, treatment was discontinued, following standard recommendations [3,24]. Treatment duration was for 24 or 48 weeks for patients with HCV genotypes 2 or 3, and 48 or 72 weeks for the remaining genotypes.

Virological assessment The concentration of plasma HCV-RNA was determined using a quantitative RT-PCR assay (Cobas Amplicor HCV MonitorTM, version 2.0; Roche Diagnostics, Barcelona, Spain), which has a detection limit of 600 IU/ml. The HCV genotype was determined by a reverse hybridization assay (Inno-Lipa HCV II; Bayer, Barcelona, Spain).

Study population All individuals examined in the present study were part of the PRESCO trial [23], an ongoing multicentre, prospective, comparative study initiated in March 2003, in which the efficacy and safety of PEG-IFN α2a plus RBV is being assessed in HCV/HIV-coinfected patients. Briefly, eligible individuals were coinfected adults never treated for HCV, with detectable HCVRNA in plasma and persistently elevated serum alanine aminotransferase (ALT) levels. Although liver biopsy was not mandatory for inclusion in the study, a substantial proportion of patients had one before initiating HCV therapy. Haemoglobin values ≥12 g/dl, leukocyte counts ≥3000 cells/µl (with neutrophils ≥1500 cells/µl), platelets ≥100 000 cells/µl and prothrombin activity, bilirubin, albumin and creatinine within normal ranges were also required. Among the exclusion criteria were the following: positivity for hepatitis B surface antigen, history of decompensated liver cirrhosis, other causes of liver disease, haemoglobinopathies, a previous history of severe psychiatric illness, cardiovascular disease or 658

Histological evaluation Liver biopsy specimens were assessed for inflammation and fibrosis using the METAVIR score [25], which grades fibrosis as 0 (no fibrosis), 1 (portal fibrosis), 2 (portal fibrosis with septa), 3 (bridging fibrosis) or 4 (cirrhosis).

Statistical analyses Baseline qualitative characteristics were expressed by their frequency (%) and quantitative features were recorded as median and interquartile ranges (IQR). The likelihood of achieving EVR was determined by intentto-treat analysis (when missing equal failures), as well as considering only subjects on treatment. Chi-square and Student’s t-tests were used to compare categorical and continuous variables, respectively. The relationship between potential prognostic parameters and EVR was examined by univariate and multivariate logistic regression analyses. The following categorical variables were analysed: HCV genotype 3, gender and antiretroviral therapy. Continuous variables included age, body © 2005 International Medical Press

Ribavirin and early response to hepatitis C therapy

weight in kg, ALT levels, CD4 cell counts, HIV-RNA and HCV-RNA levels, mg of RBV per kg of body weight and µg of PEG-IFN per body weight. In the multivariate analysis, all variables found to be associated with the dependent variable ‘EVR’ (statistically significant differences) were included. All P values were 2-tailed and differences were considered as significant when P was