Lower ribavirin biodisponibility in patients with HIV-HCV coinfection in comparison with HCV monoinfected patients

Abstract

BackgroundIn HIV infected patients, the impact of ribavirin (RBV) pharmacology on sustained virologic response (SVR) to hepatitis C virus (HCV) treatment has not been fully investigated. The objective of this study was to compare the early RBV plasma exposure between a population of HIV-HCV coinfected patients and an HCV monoinfected group.MethodsEarly RBV plasma exposure (expressed as Area Under the Curve (AUC) from 0 to 4 h) after a 600 mg first dose of RBV was measured in a population of HIV-HCV coinfected patients in comparison with an HCV monoinfected group. Peripheral blood samples were collected before the 600 mg RBV first dose (T0) to ensure no detectable baseline plasma RBV, and then 30 mn, 1, 2 and 4 hours after RBV intake (T0.5, T1, T2 and T4).ResultsEighty-six patients with chronic hepatitis C entered the study among whom 23 (27%) were HIV-HCV coinfected. Coinfected patients had a significantly lower RBV-AUC 0-4h (median: 1469 μg*h/L [range 936–3677]) compared with monoinfected patients (2030 μg*h/L [851–7700]; p = 0.018). This RBV under exposure in coinfected patients persisted after normalization of AUC to RBV dose per kilogram of body weight (182 μg*h/L [110–425] versus 271 μg*h/L [82–1091], p = 0.001).ConclusionsThese results suggest that lower early bioavailability of RBV could be one of the reasons for lower SVR in HIV-HCV coinfected patients treated with pegylated interferon/RBV combination therapy. RBV plasma underexposure seems to be associated with the immunological status of the patients with lower AUC0-4h values observed in the more immunosuppressed coinfected patients.

Peg‐interferon and ribavirin treatment in HIV/HCV co‐infected patients in Thailand: efficacy, safety and pharmacokinetics

“…The steady‐state ribavirin plasma concentrations found in this study were in the same range as previously published in HIV/HCV co‐infected patients . However, these plasma concentrations remained lower than reported ribavirin plasma concentrations in mono‐infected patients . We showed that haemoglobin concentrations dropped inversely with the raise of ribavirin plasma concentrations.…”

Daclatasvir plasma level and resistance selection in HIV patients with hepatitis C virus cirrhosis treated with daclatasvir, sofosbuvir, and ribavirin

“…4 We observed the lowest DCV concentrations in a subject (patient 6) who experienced virological failure. Also patients 1 and 3 had low levels of DCV at week 4, but they reached higher concentrations at week 8; their better outcome may be referred to these different drug kinetics or to the absence of 93H quasispecies or to the activity of the other two components of the therapy.…”

Ribavirin Concentrations Do Not Predict Sustained Virological Response in HIV/HCV-Coinfected Patients Treated with Ribavirin and Pegylated Interferon in the Swiss HIV Cohort Study

“…In a recently published study, RBV area under the curve (AUC 0-4h ) within the first hours after RBV intake was significantly lower in a small group of coinfected compared to monoinfected persons. The conclusion was that lower early bioavailability of RBV could be one of the reasons for lower SVR rates in coinfected patients [ 23 ]. Our results with similar RBV steady state concentrations in coinfected compared to monoinfected patients of other cohorts, do not support this hypothesis.…”