Actual HCV RNA levels between the LOD and LOB, and even those that fall below the LOB, can

still be reported as “detected” by the assay at a given rate as a function of the HCV RNA level. In other words, undetectable and detectable HCV RNA levels are never differentiated by a single theoretical threshold, even for an optimally performing assay. In boceprevir and telaprevir trials that included RGT approaches, eligibility for shortened treatment duration was based on achieving an undetectable HCV RNA level (i.e., HCV RNA not detected) at specific treatment timepoints. The trials were not designed to assess RGT using a 3-Methyladenine research buy timepoints.12, 13 There is a general uncertainty about whether an on-treatment HCV RNA level reported as detectable/BLOQ differs clinically from an undetectable HCV RNA level. Clinicians prescribing boceprevir or telaprevir may find it confusing when confronted with detectable/BLOQ HCV RNA measurements, particularly when deciding whether

a patient’s virologic response meets the criteria for shortened treatment duration. Understanding the clinical relevance of check details on-treatment detectable/BLOQ HCV RNA measurements with respect to treatment efficacy (i.e., SVR) can provide insight regarding the potential impact of considering 上海皓元医药股份有限公司 an on-treatment detectable/BLOQ measurement equivalent to an undetectable measurement for the purposes of RGT decisions. This report summarizes analyses

of on-treatment and follow-up HCV RNA results from selected Phase 2 and Phase 3 boceprevir and telaprevir clinical trials. These analyses were conducted to obtain a more detailed understanding of the frequency and clinical relevance of HCV RNA measures reported as detectable/BLOQ during treatment. Our analyses revealed that HCV RNA measures reported as detectable/BLOQ were common during treatment, and tended to peak in their frequency before or near key RGT decision timepoints. Furthermore, subjects with on-treatment detectable/BLOQ HCV RNA consistently had lower SVR rates compared with subjects with undetectable HCV RNA at the same timepoint. These and other analyses described in this report indicate that detectable/BLOQ HCV RNA should not be considered equivalent to undetectable HCV RNA for the purposes of making boceprevir and telaprevir RGT decisions. BLOQ, below lower limit of quantitation; DAA, direct-acting antiviral; DS, delayed start; HCV, hepatitis C virus; LOB, limit of blank; LOD, limit of detection; LLOQ, lower limit of quantitation; Peg-IFNα, pegylated interferon alpha; RBV, ribavirin; RGT, response-guided therapy; SVR, sustained virologic response. We analyzed HCV RNA results that were used for efficacy analysis purposes for selected Phase 2 and Phase 3 clinical trials of boceprevir and telaprevir.