Background:  Higher doses of ribavirin (RBV) have been associated with better virological response to anti-hepatitis C virus (HCV) therapy in HIV/HCV-co-infected patients. This study was conducted to determine the relationship between RBV plasma (RBV P) and RBV erythrocytes (RBV E) concentrations (C_min) and to correlate the RBV C_min with safety and early virological response to anti-HCV treatment.

Methods:  HIV/HCV-co-infected patients, initiating anti-HCV treatment at standard dosage (pegylated interferon-alpha [pegIFN-α] 180µg/week and RBV 800 to 1200 mg/day, according to genotype and weight), were enrolled in this prospective study. RBV C_min were determined using an high performance liquid chromatography with ultraviolet detection (HPLC-UV) at week 4 and week 12. Early virological response was defined as a plasma HCV RNA decline from baseline  of at least 2 log₁₀ copies/mL at week 12. Results were presented as median (range).

Results:  We included 22 patients. At baseline, genotype distribution was G1 (n = 10), G2 (n = 1), G3 (n = 8), G4 (n = 3); 50% had a F3-F4 Metavir score,  alanine aminotransferase (ALT) was 107 UI/L (30 to 1000), HCV RNA was 6 log₁₀ copies/mL (4.3 to 6.9) and 18 patients had HIV RNA <200 copies/mL, CD4 cell count was 377/mm³ (214 to 862). At week4, RBV P C_min and RBV E C_min, 12 hours after the last drug intake, were 1.3 mg/L (1.0 to 2.3) and 144 mg/L (35 to 325). RBV E and RBV P C_min were significantly correlated (p = 0.02). Relations between both RBV P C_min and RBV E C_min adjusted to hematocrit values and a drop in hemoglobin levels >2g/dL from baseline (p = 0.05 and p = 0.015, respectively) were observed. At week 12, 59% of patients achieved early virological response. RBV E C_min at week 4 were significantly higher in responders (154 mg/L; 101 to 325) than in nonresponders (100 mg/L, 35 to 196) at week 12 (p = 0.025) in all genotypes. The previously described plasma cut-off of 1.6 mg/L was confirmed in our study in patients with G1 and G4 (p = 0.05). An adjusted cut-off of 140 mg/L for RBV E concentration was significantly related to early virological response (p = 0.05).

Conclusions:  A clear correlation between RBV P and RBV E C_min at week 4 and the drop in hemoglobin levels was observed. Moreover, a significant correlation between RBV E C_min and a predictive cut-off for early virological response to anti-HCV treatment were shown. Therefore, an early RBV therapeutic drug monitoring might improve the management of treatment in HIV/HCV-co-infected patients.