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Genotype and phenotype basics
Jul 26, 2008

Hi Doc,

Please could you explain (in simple terms) what a genotype test is and what a phenotype test is?

I understand that they test for different things.

Regards,

Rog from UK

Response from Dr. Sherer

A genotype is literally based on your HIV virus' genetic structure. It is a description of the 'sequence' of amino acids in the RNA strand of the virus, and so researchers will speak of having 'sequenced' the virus.

What is reported to physicians when a genotype is performed is the amino acid sequence compared to the sequence in a fully susceptible 'wild type' virus with no resistance mutations. Thus we might see a test report that simply says 'wild type, no resistance mutations detected,', indicating that the virus is wild type and has no mutations.

Or, we might have a report that shows one mutation, e.g. the 'M184V' mutation, which is the signature mutation for lamivudine. This designation means that valine ('V') has replaced the usual amino acide methionine ('M') at the 184th codon in the genetic sequence.

Over time, we have learned which of these types of replacements are associated with reduced susceptibiility to a drug and drug resistance, and these are called primary resistance mutations. Other mutations whose role is unknown, or of lesser importance, are referred to as secondary mutations.

Genotype tests occassionally will show a mutation that initially is without evidence of any impact on viral loads, but which over time leads to viremia and virologic failure.

In contrast, a phenotype test is a measure of the ability of a single patient's virus to replicate in the presence of each ART drug. It is performed by gradually increasing the concentration of each drug in a test tube and observing the growth of the virus at each concentration.

A phenotype is reported to physicians as a comparison of the patient's specific virus to a known control 'wild type' virus. Hence, if no mutations are present, the patient's virus performs exactly as does the wild type virus, and the report says that the virus is 'wild type.'

If, on the other hand, the patient has failed an efavirenz-containing regimen and has a K103N mutation, which is one of the primary resistance mutations for efavirenz, the phenotype test might be reported as a "60-fold reduction in susceptbility to EFV", compared to wild-type virus.

While the genotype and phenotype measure different aspects of resistance, they are providing similar types of information. In all cases, the phenotype results from the genotype, i.e. usually a structural change will occur first, and soon thereafter a phenotypic change will result.

In the above example, the patient who is failing an EFV-based regimen first develops the K103N resistance mutation, and then, within a short period of time, their phenotype will also show reduced susceptibility of the patient's virus to EFV.

I advise you to ask your doctor this question, and take a copy of this response with you. He or she may be able to more fully apply this information to your specific situation.


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