DOI: 10.1097/QAI.0b013e3181b62858
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PMID: 19858925
Issn Print: 1525-4135
Publication Date: 2009/11/01
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Excerpt
Treatment combining peginterferon alfa plus ribavirin is proposed to treat hepatitis C virus (HCV) infection in HIV-infected patients.1 In a clinical trial, sustained virological response (SVR) was obtained in 29% and 62% of patients infected with HCV genotypes 1 and 2 or 3, respectively.2 Factors explaining these lower SVR rates in comparison with HCV-monoinfected patients remain to be determined. Because of potential toxicity, patients received low dosage of ribavirin (400 mg twice a day),2 in part contributing to low SVR. Indeed, studies have demonstrated a relationship between ribavirin exposure and anti-HCV therapy efficiency in HCV monoinfected3 and HIV-coinfected patients4 previously untreated for their hepatitis C. In this study, we assessed the impact of ribavirin plasma levels on SVR in patients previously treated for their hepatitis C without HCV clearance and receiving peginterferon alfa plus ribavirin as retreatment.
HIV-1-infected patients aged 18-65 years with chronic hepatitis C previously treated without virological response were eligible for the study. They had previously received a first anti-HCV treatment as follows without virological response: (1) interferon alfa alone at least 3 MU 3 times per week for at least 12 weeks; (2) interferon alfa at least 3 MU 3 times per week and ribavirin at least 600 mg per day during a minimal duration of 24 weeks. They had a CD4 cell count >200 cells per microliter and a plasma HIV RNA level <10,000 copies per milliliter (Versant HIV-1 RNA 3.0 Assay; Bayer Corporation, Berkeley, CA; cutoff 50 copies/mL), with or without antiretroviral therapy. Patients received pegylated interferon alfa-2a (Pegasys, Produit Roche, 180 μg subcutaneously once a week; Neuilly-sur-Seine, France) and ribavirin (Copegus, Produit Roche, 800, 1000, or 1200 mg twice per day for a bodyweight <65 kg, between 65 kg and 85 kg, and ≥85 kg, respectively) for 48 weeks. HCV genotype was determined at the beginning of the study (TruGene 5′NC HCV Genotyping Assay; Bayer Diagnostics, Tarrytown, NY). The plasma HCV load (Cobas Amplicor HCV Monitor 2.0; Roche Diagnostics, Meylan, France, cutoff 600 IU/mL) was measured before and at weeks 4 and 12 of the treatment. SVR was defined as plasma HCV RNA undetectability 24 weeks after the end of the treatment, nonresponse if HCV RNA was detectable at this time.
The ribavirin concentration was measured on stored frozen plasma from blood samples taken 2 and 12 weeks after treatment initiation and collected before the next dose of ribavirin. Samples were processed in the 2 hours after blood sampling and were kept frozen at −80°C. Ribavirin concentrations were measured using an automated solid phase extraction process and a validated high-performance liquid chromatography-ultraviolet assay adapted from previously published methods5,6 at weeks 2 and 12 after treatment initiation. Association between trough plasma concentration of ribavirin (RBV C0) at these times and SVR was determined according to the best cutoff.
Analysis of HCV treatment efficiency was conducted on an intention-to-treat basis. The value of efficacy cutoff was evaluated by considering the median, the first, and third quartiles of the concentration of ribavirin, respectively. To compare the proportions of patients who achieved a SVR, a χ2 or a Fisher exact test was used. For each comparison, patients were divided in 2 groups after the observed plasma RBV C0 (≤ or >cutoff). For each series of experiments, the variability of ribavirin concentration was estimated by determination of the relative standard deviation.
Seventeen patients {14 males, median age 39 [interquartile range (IQR)] (28-44)} were included in the study. The median CD4 T-lymphocyte count was 609/μL (IQR 302-1140) at the initiation of anti-HCV therapy. All the patients received an antiretroviral treatment, 12 had an undetectable HIV RNA level.
