What is Antivirogram?

The Antivirogram® is a conventional phenotypic resistance assay that measures, in controlled laboratory conditions, the level of resistance of the HIV population derived from an individual patient to each of the currently approved NRTI, NNRTI and PI. This resistant 'behavior' of the virus usually represents the combined net effects of many different mutations and the complex interactions between them, including genetic changes that have not even been identified yet. Contrary to genotyping, phenotypic resistance testing provides a direct measure of resistance.

In addition, the Antivirogram® provides a quantitative measure of viral resistance to all the currently approved NRTI, NNRTI and PI drugs, measured as the inhibitory concentration 50% (IC50) - the concentration of each drug required to inhibit growth of the virus by 50%. A patient's sample virus IC50 is compared to the IC50 for fully sensitive, non-mutated 'wild-type' virus and the level of resistance of the sample virus is expressed as the Fold-Change in IC50 (FC) compared to wild type. For example, if a wild type virus requires 0.5 µM of drug A to reduce its growth by 50% and the sample virus required 5 µM of the same drug, this yields a FC value of 10. This process is repeated for every drug, and the report contains all drug-specific FC values for the sample virus. The Antivirogram® report enables physicians to identify the drug(s) to which the sample virus has developed decreased susceptibility, and thus helps in the selection of the optimal combination of drugs for each individual patient.

There are several key differences between the Antivirogram® and other phenotypic assays:

• The recombinant virus that is used in the Antivirogram® assay, and that is derived from the patient's virus, includes the full coding region for the protease gene as well as the largest fragment of reverse-transcriptase (RT) coding region (up to amino acid 400). Other assays include shorter fragment potentially excluding important genetic determinants of resistance to RT-inhibitors. (see How the Antivirogram® works).
• The Antivirogram® has been shown to work with all Group M subtypes.
• The Antivirogram® is the only phenotypic assay that has been proven in a prospective controlled clinical trial more useful than standard of care in helping the selection of active drugs leading to improved virological outcomes.
• At the end of 2000, the Antivirogram® became the first phenotype assay to have drug-specific biological cut-offs.

References

1. Mazotta, F. et al., _Real versus VirtualPhenotype to guide treatment in heavily pretreated patients: 48-week follow-up of the Gentipo-Fenotipo de Rezistencia (GenPheRex) Trial, J. Acquir Immune Defic Syndr 2003; 32:268-280 2. Saracino A. et al., "Change of antiretroviral therapy guided by Genotypic or Phenotypic Resistance testing: an open-label, randomized, multi-center study" (PhenGen). Poster 3.8 presented at the 1st European HIV Drug Resistance Workshop, Luxembourg. 3. Perez-Elias M.J., et al. and the Realvirfen Study Group. "Phenotype or VirtualPhenotype for choosing antiretroviral therapy after failure: a prospective, randomized study." Antiviral Therapy 2003; 8: 577-584