Cut-offs for Antivirogram

The Antivirogram® assay uses Biological Cut-Off (BCO) values to separate viruses that are susceptible to a drug from those that show signs of resistance. BCO are derived from in vitro experiments and are drug-specific.
 

First Generation BCO

The first generation Antivirogram® BCO were defined as the geometric mean of the FC values measured for > 1,000 clinical isolates from treatment-naïve patients plus 2 Standard Deviations. Thus, when a FC test result was higher than the BCO it could be classified as being 'above the normal susceptibility range' with 97.5% confidence.

A limitation of these first generation BCO was that they gave a snapshot view of the natural variation of phenotypic susceptibility of wild type viruses at a given time so a new approach was adopted to calculate the second generation BCO.
 

Second Generation BCO

Rather than starting from a fixed set of clinical samples obtained from treatment naïve patients, the second generation approach uses the power of Virco's genotype database to define 'Wild Type viruses'.

For each drug Virco has defined a specific set of resistance-associated mutations based on extensive analysis of a large dataset of paired genotype and phenotype results from clinical isolates. Some of these mutations cause resistance to only one drug, whereas others may affect the virus' susceptibility to multiple compounds or even an entire class. A virus is considered fully susceptible or 'Wild Type' to a drug when it does not harbor any of the pre-defined resistance associated mutations for that drug. Since the resistance-associated mutations are drug-specific a virus can be 'Wild Type' for one drug, and not another. The number of 'Wild Type' viruses per drug found in Virco's genotype database varies between 246 for DDI and 3981 for ETR (status February 2009). These drug-specific 'Wild Type' viruses form the basis for the calculation of the second generation BCO. Note that the term 'Wild Type' used in this context does not necessarily mean that the virus does not carry ANY resistance-associated mutations.

The second generation Antivirogram® BCO is the 97.5th percentile of 'Wild Type' FC values per drug (after outlier removal). For more details about the exact calculation methods, please consult the poster library section.

When available, Antivirogram® uses Clinical Cut-Offs in addition to the Biological Cut-Offs in order to make a resistance call.