Erythrocyte and plasma ribavirin concentrations in the assessment of early and sustained virological responses to pegylated interferon-alpha 2a and ribavirin in patients coinfected with hepatitis C virus and HIV

To determine the relationship between erythrocyte and plasma ribavirin concentrations in hepatitis C virus (HCV)/HIV-coinfected patients, and to correlate ribavirin exposure with early and sustained virological response (EVR and SVR) and haemoglobin level reductions. Clinical and biological data from 68 HCV/HIV-coinfected patients were recorded at baseline, week 4 (W4), week 12 and at 24 weeks after completion of treatment. Plasma and erythrocyte ribavirin concentrations were determined 12 h after the final ribavirin dose (C-min). Erythrocyte ribavirin concentrations were 100-fold higher than plasma concentrations, with a significant relationship between them (P0.05). In patients with HCV genotype 1 or 4, a plasma ribavirin C-min threshold of 1.95 mg/L at W4 tended to predict EVR [sensitivity 44; specificity 87; AUC 0.67 (95 CI 0.500.84)] and was predictive of SVR [sensitivity 58; specificity 84; AUC 0.71 (95 CI 0.510.90)]. Among patients with these HCV genotypes, an erythrocyte ribavirin C-min threshold of 146 mg/L at W4 was found to be the best value for discriminating between responders and non-responders for both EVR [sensitivity 67; specificity 75; AUC 0.58 (95 CI 0.240.93)] and SVR [sensitivity 50; specificity 80; AUC 0.70 (95 CI 0.391.01)]. We also demonstrated a significant relationship between reduced haemoglobin levels and plasma ribavirin C-min at W4 (P0.05). Therapeutic drug monitoring may be useful for the management of anti-HCV treatment in HCV/HIV-coinfected patients.