A new standard-of-care for the treatment of chronic

HCV genotype 1 infection has emerged with the recent regulatory approval of the HCV NS3/4A protease inhibitors boceprevir and telaprevir. These direct-acting antiviral (DAA) drugs, each to be used in combination with pegylated interferon-alpha Selleck Vismodegib plus ribavirin (Peg-IFNα/RBV), significantly improve SVR rates versus Peg-IFNα/RBV alone.6–11 One of the benefits with the use of telaprevir or boceprevir is the opportunity to shorten the total duration of therapy from 48 weeks to 24-36 weeks in a large proportion of patients with HCV genotype 1 infection without compromising treatment efficacy. Treatment duration for each drug is selleck chemicals llc based on multifaceted, clinically validated RGT approaches that are not only unique to each drug, but are also unique to specific patient populations using the specific drug.12, 13 Although the opportunities for greater treatment efficacy and shorter treatment duration provided by these drugs are welcomed, the complex nature of the RGT decision rules raises concerns about the potential

for misinterpretation, which could result in suboptimal patient care. Therefore, providing adequate justification for RGT decision rules, and minimizing any potential sources of confusion, may help optimize the use of these drugs in clinical practice. The boceprevir and telaprevir Phase 3 trials used the Roche COBAS TaqMan HCV 2.0 assay. For these trials

the lower limit of plasma HCV RNA quantitation (LLOQ) was considered 25 international units per mL (IU/mL), and the limit of detection (LOD) was considered 9.3-10 IU/mL. Figure 1 summarizes our basic interpretation of HCV RNA results based on a hypothetical and medchemexpress optimally performing quantitative HCV RNA assay with an LLOQ of 25 IU/mL and LOD of 10 IU/mL. In general, there are three different qualitative levels of HCV RNA that are reported using this assay: Quantifiable, reported as a specific IU/mL number that is ≥25; detectable but below the LLOQ (detectable/BLOQ), reported as “<25 IU/mL” or “HCV RNA detected <25 IU/mL”; or undetectable, reported as “HCV RNA not detected” or “target not detected.” The LLOQ is the lowest HCV RNA level that is within the linear and analytically acceptable range of the assay, and the LOD represents the lowest HCV RNA level that is detected ≥95% of the time. The limit of blank (LOB, considered 1 IU/mL in this example) is determined by testing of blank (i.e., non-HCV) samples, and represents the minimum assay readout cutoff for calling an HCV RNA level “detected.” A common misconception is that the assay LOD is the minimum actual HCV RNA level for any result reported as “detected.” Considering that the LOD represents the lowest actual HCV RNA level with a ≥95% detection rate, HCV RNA levels that equal the LOD theoretically should not be detected <5% of the time.