Virco TYPE HIV-1 FAQ

• What is virco®TYPE HIV-1
• Why is virco®TYPE HIV-1 different from other resistance tests?
• Wouldn't a conventional phenotype be a better predictor of drug susceptibility than a computer-generated analysis?
• Why is the virco®TYPE HIV-1 an improvement over the current methods of resistance testing?
• Why not just perform a conventional phenotype instead of a virco®TYPE HIV-1?
• How does the Virtual Phenotype engine work?
   

What is virco®TYPE HIV-1

Virco® TYPE HIV-1 is a quantitative, biologically- based, objective, data-driven system for predicting HIV-1 drug susceptibility from a viral genotype. Virus from the patient is sequenced and software then searches our database (the largest in the world with approximately 37,000 matching genotype/phenotype pairs covering more than 5,000 different patterns of resistance) for previous samples with the same patterns of resistance mutations. The phenotypes for these matching samples are then retrieved from the database and an average resistance figure (change in IC50) calculated for each drug in turn. Studies have demonstrated this to be a highly reliable predictor of real phenotype and of treatment response.
 

Why is virco®TYPE HIV-1 different from other resistance tests?

While genotyping with rules-based interpretation may be the least expensive test, it provides only a qualitative result that in some cases may not correctly take into account the interactions that may exist between mutations. Phenotyping, on the other hand, provides a quantitative measure of drug resistance taking into account mutation interactions, but is expensive and time-consuming. virco® TYPE HIV-1, the genotype with quantitative phenotypic analysis, combines the best of both worlds. It is the first resistance test that provides phenotypic information and expert clinical knowledge in an easy-to-read report at a fraction of the cost of a conventional phenotype, and is the only resistance test in which consistently derived clinical cut-offs can be applied.
 

Wouldn't a conventional phenotype be a better predictor of drug susceptibility than a computer-generated analysis?

Probably not. The virco® TYPE HIV-1 test makes use of phenotypic predictions generated with the VirtualPhenotype bio-informatics engine, and are based on the average of multiple conventional phenotypic test results. These predictions are clinically equivalent to, and more accurate than, a single conventional phenotype assay since they are based on multiple measurements rather than on a single one. In addition, they are provided more rapidly and at a fraction of the cost of a conventional phenotype.
 

Why is the virco®TYPE HIV-1 an improvement over the current methods of resistance testing?

Virco® TYPE HIV-1 is the worlds first quantitative biologically-based accurate system for predicting HIV drug resistance from the genotype and is proving to be a significantly more reliable predictor of which drugs will and will not work for a given patient than existing genotypic interpretation methods. The difficulties facing anyone, however expert, in the interpretation of 'raw' genotypic information are considerable. There are over 250 individual mutations known to affect HIV drug resistance; they interact in complex ways; some mutations cause resistance on their own, some in combination; some cause resistance to a number of different drugs; some cause resistance to one drug and reverse it to another etc. It is, therefore, very difficult to translate genotypic information into a reliable prediction of the drugs that the virus would be able to resist and those to which it would be sensitive. Current approaches to interpretation involve one or more of the following: Subjective judgment (educated guesswork); Application of tables of mutations and the drugs they affect resistance to; Application of 'rules-based' algorithms (essentially a more systematic version of 2). But as the IAS pointed out in their recommendations published in JAMA, 'Extensive variations exist among the different available algorithms', and 'An alternative approach to interpretation of genotype is the 'virtual phenotyp''. (Hirsch MS et al. (2003), CID 37: 113-128). In addition, the EURO Guidelines recommend that 'for the interpretation of resistance data, clinically validated systems should be used to the greatest extent possible' (Vandamme AM et al. (2004), Antiviral Therapy 9: 829-848).

Virco has one of the the largest repositories of resistance information in the world - a database of around 60,000 (January 2008) datasets of matching genotypes and phenotypes. Our unique approach is to sequence the patient's virus, compare the sample sequence to a reference sequence, and for each drug, identify identify all mutations and mutation pairs in the sample virus that contribute to resistance to a given drug.

In two retrospective studies of major cohorts one performed by Virco comparing virco®TYPE HIV-1 predictions to those of 3 genotypic interpretation systems for entire treatment regimens and another independent analysis examining a number of methods for predicting response to tipranavir, it was shown that virco®TYPE HIV-1 response predictions provided the strongest correlation with virological response of any of the algorithms examined.
 

Why not just perform a conventional phenotype instead of a virco®TYPE HIV-1?

Conventional phenotyping remains a widely used test when it comes to interpret the potential interactions that may exist among mutations on a single viral genome since it provides a direct, quantitative assessment of the virus' ability to grow in the presence of each available antiretroviral drugs. In this sense, virco® TYPE HIV-1 still offers some advantages over conventional phenotyping in that: it is less costly, and faster (48 hours after the genotype is received compared with 15 working days for conventional phenotyping); it is more sensitive than conventional phenotyping since it provides susceptibility information on the resistant virus present in a mixture of resistant and susceptible viruses rather than on the mixture itself. Moreover, virco® TYPE HIV-1 provides fold-change information derived from multiple measurements, a strategy that removes the intrinsic variability associated with conventional phenotype single-measurements. Virco anticipates that physicians will continue to use conventional phenotyping in addition to genotyping and virco® TYPE HIV-1, particularly for patients with complex treatment histories or who are being treated with investigational drugs or new drug combinations.
 

How does the Virtual Phenotype engine work?

Virus from the patient is sequenced (genotyped) and software then searches our database (the largest in the world, with paired genotype/phenotype results on more than 32,000 isolates containing a wide diversity of mutational profiles) for previously studied samples with similar patterns of resistance mutations. The conventional phenotype information for these matching samples are then retrieved from the database and an average resistance value (also known as fold change in IC50) is calculated for each drug in turn. Studies have demonstrated this to be a highly reliable predictor of conventional phenotype derived-values and of treatment response.