Pharmacokinetic (PK) interactions between boceprevir (BOC) and atazanavir (ATV/r) or raltegravir (RAL) in HIV/HCV-co-infected patients (pts). ANRS HC27 study
Background: There are PK interactions between BOC and HIV PIs in healthy individuals. The aim of this study was to investigate the impact of BOC on ATV/r and RAL PK in HIV/HCV co-infected pts.
Methods: In this multi-center open-label phase II trial, treatment-experienced HIV/HCV genotype 1 pts well suppressed on ART (HIV VL < 50 cp/mL) received peg-IFN2b (1.5 µg/kg/wk) + RBV (800 to1400 mg/d) + BOC (800 mg tid) after a 4-week lead-in phase (peg-IFN+RBV). Allowed ARVs were: TDF, FTC/3TC, and ATV/r (300/100 mg qd) or RAL (400 mg bid).PK parameters Ctrough(Cτ), Cmax and AUC0-8h were determined at baseline and after 4 weeks of BOC (W8). Drugs levels were measured by LC-MS/MS. PK calculations were done by a non compartmental method.
Results: 17 pts enrolled 12 pts completed the PK study, 7 with ATV/r and 5 with RAL. BOC co administration reduces exposure of ATV by 50.5% (p=0.01) but increases RAL exposure by 56.7% (p=0.312). It also reduces ATV Cτ, Cmax and RAL Cτ by 33.5%, 54% and 54.4% respectively, but increases RAL Cmax by 156.4% even statistical significance was never reached. Mean ARVs Cτ were maintained in the recommended range. Historic comparison for BOC exposure showed a decrease of AUCτ and Cmax by 13.6% and 45.6% and by 32.2% and 31.3% when combined with RAL and ATV/r respectively, meanwhile its mean Cτ increase in both combinations by 31.3% (RAL) and 71.5% (ATV/r).
Conclusions: With the limitations of this small study, there was a trend towards lower ATV PK parameters when ATV/r was combined with BOC that was significant only for AUC. There was substantial variability in RAL PK parameters with a trend towards higher RAL AUC0-8h and Cmax and lower RAL Cτ which were not statistically significant. BOC PK was unaffected. Pending more data, carefully monitoring of HIV replication in pts under ATV/r or RAL-based regimens receiving BOC would be appropriate.
R. Garraffo, ANRS HC 27 BOCEPRE VIH Study Group
University Hospital Pasteur and School of Medicine of Nice, Clinical Pharmacology, Nice, France