Incidence of virological failure and emergence of resistance with twice-daily vs every 8-h administration of telaprevir in the OPTIMIZE study.

The OPTIMIZE study demonstrated noninferior efficacy between telaprevir (TVR) twice daily (bid) vs every 8-h (q8h) administration. This analysis compared the selective pressure of both dosing regimens by characterisation of the hepatitis C virus (HCV) variants emerging in genotype 1 (G1) HCV-infected patients who did not achieve sustained virological response (SVR). HCV NS3•4A population sequencing was performed at baseline and time of failure (viral breakthrough, stopping rule or relapse). TVR-resistant variants were classified by fold change in inhibitory concentration (IC50 ). Baseline TVR-resistance was low (<5%) and did not preclude achieving SVR in either arm. The proportion of patients with TVR-resistant variants at time of failure was similar in the bid (15%) and q8h (17%) dosing arms. The majority of variants and virological failures occurred in G1a patients, and mutations V36M, R155K and R155T (G1a), and V36A, T54A and A156S (G1b) were significantly enriched in both treatment arms. The number and type of emerging TVR-resistant variants in non-SVR patients were comparable between treatment arms and were consistent with previous observations. No differences in viral resistance profiles were observed between TVR-based treatment arms in non-SVR patients, indicating a similar selective pressure of TVR bid and q8h dosing.

RCT Entities:   Population Interventions Outcomes