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HIV Drug Resistance and Resistance Testing

2001

What is Genotypic Testing?

Genotypic resistance testing examines the actual structure -- or genotype -- of HIV taken from a patient (a standard blood sample is all that is required). The HIV is examined for the presence of specific mutations that are known to cause resistance to certain drugs.

An example: As discussed in "How Do Mutations Occur Before Antiretroviral Therapy Is Started?", researchers know that Epivir is not effective against forms of HIV that contain the mutation M184V in its reverse transcriptase enzyme. If a genotypic resistance test discovers a mutation at position M184V, chances are that the person's HIV is resistant to Epivir and is not likely to respond to the drug.

For many drugs, including the protease inhibitors, complex patterns of mutations are required for resistance to occur.

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To conduct a genotypic test, laboratories use PCR technology to make many copies of, or "amplify," the HIV genetic material. Once amplification has been completed, the genetic sequences of particular viral enzymes -- such as reverse transcriptase and protease -- can be examined carefully for mutations. Depending on the type and number of mutations found, the laboratory can determine whether someone has developed resistance to a specific drug, since almost all drugs follow a set pattern of mutations.

There are actually two types of genotypic tests: sequencing assays and point-mutation assays. Sequencing assays look for any mutation in either the reverse transcriptase or protease enzymes. Point-mutation assays look for key mutations in these enzymes that are known to cause drug resistance. Most laboratories use point-mutation assays, as they are easier (and cheaper) to perform and their results are easier to interpret.

For genotypic tests to be accurate, they generally require the use of a blood sample from a person who is actively taking antiretroviral medication and has a viral load higher than 1,000 copies/mL.

If therapy is stopped before blood is drawn for a genotypic test, the wild-type virus in the body may outgrow the mutant virus. In turn, the results may not show any drug-resistant mutations, but the drug-resistant strain may still remain at very low numbers in the person's body and may quickly increase when therapy with the same drugs is restarted.

Genotypic resistance testing can take as little as a few days to complete. A single genotypic test can cost between $300 and $500.




  
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This article was provided by AIDS Community Research Initiative of America. Visit ACRIA's website to find out more about their activities, publications and services.
 

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