New Phenotype Resistance Testing Standards from Virco

One of the concerns about using resistance testing has been that the cutoff between resistance and sensitivity for a person on a given drug may be off. This concern were raised repeatedly by researchers at this past Summer's Resistance Workshop. You can read about this in more detail on the NATAP web site in the Conference Reports section and then look for the Resistance Workshop Reports. Alternately, you can read about it in the NATAP Reports newsletter Summer Edition, which is posted on the NATAP web site and easily found on the front page of the site. For example, up until now if a person's sample were submitted to Virco for phenotypic testing the results would say, for a given drug, that the person was either below 4-fold or above 4-fold or below or above 10-fold in sensitivity. So there were 2 cutoffs, which was the same for all drugs. Virco announced at Glasgow that they are changing the cutoffs. Now, there is a different cutoff for each drug. And the cutoffs are different if you are using the phenotype test or the virtual phenotype test. The virtual phenotype test uses a computer analysis to compare a patient's genotype test results to thousands of previously submitted samples of other patient's genotypes. The computer looks at the phenotypes of all the previously submitted genotypes matching the patient's sample. Based on a computer analysis of all those phenotypes, Virco generates a "virtual phenotype" for that patient, without actually running a phenotype test. Of course, the benefit is that you can get back a "virtual" phenotype result more quickly than a phenotype test result.

There is another company that offers phenotypic testing, and they are called Virologics. They also offer genotypic testing and are based in South San Francisco, CA. They have one cutoff for phenotypic testing, and its 2.5 fold. Their test results also provide a graph depicting how much above that level a patient's resistance is. The Virologics tests are commercially available through large blood testing laboratories. VGI (Visible Genetics, Inc) provides only a genotypic test and is not yet commercially available (FDA approved), but in New York City it can be accessed through a local lab. VGI is located in Toronto, Canada.

Here is an explanation of the new test, cutoffs, and definitions as offered by Virco:

HIV-1 evaluated by any of the tests in the Virco HIV drug resistance monitoring range is categorized as either "within the normal range of susceptible virus" or "above the normal range of susceptible virus - reduced susceptibility. The normal range of susceptible virus has been determined by performing phenotypic resistance tests on 1,000 untreated HIV+ individuals and for several thousand samples of genetically wild type virus. The results are different for different drugs, highly concordant between the two analyses and form the basis on which the cut-offs below are derived. The cutoffs for the Antivirogram ^TM phenotype test are set at 2 standard deviations above the mean value for untreated or wild type virus. This means that any IC50 values above this point can be said to be above the normal susceptible range with 97.5% confidence. The table below contains the new cutoffs for both the phenotype and virtual phenotype test, and as you can see they can be different values.

*Denotes the upper limit of the normal susceptible range.  

Virco also says on their report:

a patient's response to therapy depends on multiple factors including the percentage of a patient's viral population that is resistant, drug pharmacokinetics (PK), and medication compliance. Therefore, this test result should be interpreted in conjunction with the patient's antiretroviral treatment history, viral load count, and clinical status when making therapeutic changes

The test may be unsuccessful if the plasma HIV rNA viral load  is <1000 copies/ml of virus per ml of plasma, measured  with Roche Amplicor Monitor Assay.

Virco tests can be accessed through LabCorp. As well, Virco has a lab of its own located at the Johns Hopkins University Bayview Campus, 5210 Eastern Ave., Baltimore, MD 21224.