Unlike genotypic testing, which looks for particular genetic mutations that causes drug resistance, phenotypic testing directly measures the sensitivity -- or phenotype -- of a patient's HIV in response to particular antiviral drugs.
Phenotypic resistance tests measure the concentration of a drug required to inhibit viral replication in the test tube by a defined amount such as 50% or 95%. This is called IC50 or IC95. IC stands for inhibitory concentration. In other words, a laboratory conducting a phenotypic test is trying to determine the amount of drug needed to stop HIV from reproducing. If it only takes a standard amount of the drug -- a concentration equal to that used by HIV-positive people -- HIV is not resistant to the drug. If higher amounts of the drug are needed to stop HIV from reproducing, HIV is considered to be resistant to the drug being tested.
The concentration of drug necessary to inhibit virus replication is expressed in units called nanomoles (nM). For example, if the IC50 of the wild-type virus is 100nM and that of the test virus is 400nM, the test virus is considered to be fourfold resistant to the drug being tested. In other words, HIV in the patient is fourfold less sensitive to the drug.
Because phenotypic testing directly measures the sensitivity of the virus to particular drugs, many researchers believe that these tests are more comprehensive and trustworthy than genotypic tests.
Phenotypic resistance testing procedures are relatively complex and can take longer than genotypic tests to produce accurate results -- from ten days to several weeks. They are also more expensive than genotypic tests. A single phenotypic test can cost between $700 and $900.
Phenotypic tests cannot evaluate the sensitivity of small HIV populations found in a blood sample. For example, there might be a population of HIV that is not sensitive to Epivir. Unless this particular strain accounts for more than 10% to 20% of the HIV population found in a blood sample, chances are that it will not be recognized by the test.
Another challenge is that researchers still do not fully understand what level of resistance translates into a failure of treatment. For example, a five-, six-, or sevenfold reduction in the sensitivity of HIV to a protease inhibitor is considered "moderate." But is there a significant difference between a fivefold reduction and a sevenfold reduction? Researchers are still trying to figure out what level of resistance determines that a drug is no longer useful.
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