Use of BCO / CCO
For most drugs, Virco uses two Clinical Cut-Offs (CCOs) as the basis for interpretation of resistance. These Cut-Offs were defined using clinical outcome data and indicates the FC (Fold Change) levels associated with either 20% loss of drug activity (loss of the ability to maximally reduce viral loads, CCO1) or 80% loss activity (CCO2). Virco has also determined biological cut-offs (BCOs) for all drugs, which are based on in vitro drug susceptibility testing of "wild-type" viruses, and indicate the upper limit FC of the range of test results obtained for such wild type strains.
For a number of drugs, the CCO1 (FC associated with 20% loss of drug activity) is actually below the BCO. For three drugs (lamivudine, etravirine, and nelfinavir) an unexpectedly high number of samples with no evidence of exposure to ARV drugs have FC levels slightly above CCO1, leading to a "Reduced Response" resistance interpretation. Although we have demonstrated that the CCOs provide accurate and consistent interpretations of resistance in drug-experienced patients for these drugs, there is currently no clinical evidence to suggest that the response to any of these drugs in samples with no evidence of exposure to ARV drugs is compromised by such modest alterations in susceptibility. In order to reduce the possibility of confusion about the activity of these drugs, vircoTYPE HIV-1 assay version 4.3.00 uses a combined BCO / CCO analysis for interpreting resistance for these three drugs.
For resistance interpretation of lamivudine, etravirine, and nelfinavir, all samples with FC less than or equal to the BCO are classified as "Susceptible", viruses with FC between the BCO and CCO2 are classified as "Reduced Response", and viruses with FC>CCO2 are classified as "Minimal Response". For samples with FC
On page two of the report Virco uses the BCO in place of the CCO1 in the drug specific bar graphs for etravirine, nelfinavir, and lamivudine, but additionally lists the BCO values and both the lower and upper CCOs next to each of these drugs.
