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resistance testing
Apr 23, 2007

I'm confused about resistance testing. When talking about phenotype testing, what is meant by "cut-offs" and "fold changes".

Response from Dr. Sherer

A genotype resistance test measures the sequence of virus, and thus results refer to specific mutations, M184V is a substitution of Methionine (Met) for Valine (Val) at the 184 locus.

In contrast, results for a phenotype are given in relation to the difference, if any, between YOUR virus and 'wild-type' virus, i.e. a virus with no mutations. So we speak of one who has the M184V mutation, which confers reduced susceptibility to lamivudine, as having an '8-fold' reduction in susceptibility, i.e. it is 8x less susceptible with the mutation than another virus without the mutation.

The big question is, what does this mean to you in the clinic? For this answer, we need to know what happens to patients who have an 8-fold reduction in susceptibility, i.e. at what clinical 'cut-off' of susceptibility is there a 20% loss of anti-viral activity (SOME resistance) and at what clinical cut-off is there an 80% loss of anti-viral activity (NEAR TOTAL resistance).

These terms are confusing even to experienced clinicians, so I urge you to take these answers to your doctor and talk to him or her about them, in the context of your own test results. Hopefully that will lead to some clarity on the meaning of these terms.


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