Abstract Body

Background: Potent oral directly acting antiviral (DAA) HCV therapy with low pill burdens and short therapeutic courses are promising replacements for interferon and ribavirin based regimens. The impact of these improvements on patient adherence and virologic outcomes has not been described. Methodology: Sixty HCV infected, treatment naive, genotype 1 patients were enrolled into 3 arms of a phase 2 clinical trial and received: sofosbuvir + ledipasvir (400/90mg one pill once daily in a fixed dose combination (FDC)) for 12 weeks, FDC + GS-9451 (80mg/day), two pills, once daily for 6 weeks, or FDC + GS-9669 (500mg/day), three pills, once daily for 6 weeks. Serial measurements of virologic correlates (HCV RNA; deep sequencing of viral mutations) were performed. Adherence was measured using three tools: MEMS caps (MEMS), pill counts (PC) and patient report (PR). Demographics and modified ACTG questionnaires were used to determine risk factors for non-adherence. Adherence tools, treatment arms, and risk factors were compared using Pearson correlations, T-tests/ANOVA and Chi-squared tests respectively. Results: Patients enrolled were African American (88%), male (72%) with ≤ 12th grade education (61%). Psychiatric disease (43%) and recent history of drug/ETOH abuse (37.5%) were common. Adherence to DAA regimens declined with increasing pill burden (99.3 } 1.6% vs. 97.2 } 3.6% vs. 94.8 } 7.4%, one, two & three pills/day respectively, p=0.02 (Fig 1A)). Adherence to therapy declined significantly during the 12-week treatment course (98.1 } 0.9% vs. 95.0 } 1.2% weeks 0-4 vs. weeks 8-12, p=0.04 (Fig1B).) Missed doses by MEMS correlated with PC (R2=0.24, p<0.0002), but neither with PR (p=0.14 & p=0.84 respectively). Three patients missed ≥2 consecutive doses. Adherence was similar in patients with and without early viral suppression (