PII-021 - QUANTIFYING THE EFFECTS OF ALCOHOL USE ON DRIED BLOOD SPOT CONCENTRATIONS OF SOFOSBUVIR’S ACTIVE METABOLITE, 007-TP, IN PERSONS WITH HEPATITIS C USING PHOSPHATIDYLETHANOL AS AN OBJECTIVE BIOMARKER OF ALCOHOL CONSUMPTION.

L. Salah, M. Morrow, K. Brooks, J. Kiser; University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Background: Antivirals achieve high cure rates in persons with Hepatitis C virus (HCV), but there are limited data on the impact of alcohol use on antiviral pharmacology. This analysis assessed the effect of alcohol use, measured using the objective biomarker phosphatidylethanol (PEth), on concentrations of sofosbuvir’s active metabolite, GS-331007 triphosphate (007-TP), in dried blood spots (DBS).

Methods: INCLUD was a prospective, open-label study in 60 individuals with HCV and self-reported (SR) ongoing heavy alcohol and/or drug use treated with ledipasvir/sofosbuvir (Harvoni®, Gilead Sciences, Foster City, CA) orally once daily for 12 weeks. PEth (lower limit of quantification: 5 ng/mL) and 007-TP were measured in DBS biweekly during treatment using validated LC-MS/MS assays. Repeated measures correlation was used to determine the correlation between SR alcohol use and PEth. A linear mixed model was used to analyze the effect of PEth on log-transformed 007-TP DBS concentrations.

Results: PEth was detected in 59% (288/384) of participant samples, with mean (range) PEth concentrations of 258 ng/mL (below limit of quantification to 3656 ng/mL). SR alcohol use and PEth in DBS were moderately correlated (rmcorr = 0.43 [95% CI: 0.34, 0.52]). By intention to treat, 87% were cured of HCV. In a previous model adjusted for factors influencing 007-TP levels in DBS, the addition of PEth was not significantly associated with 007-TP [0.11% increase for every 10-unit increase in PEth [95% CI: -0.04%, 0.26%], p=0.138).

Conclusion: SR alcohol use and PEth levels were not strongly correlated, highlighting the need for objective measures of alcohol use. High cure rates were observed and PEth was not associated with 007-TP, indicating ongoing heavy alcohol use should not preclude HCV treatment.