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HIV Drug Resistance and Resistance Testing

2001

How Are Genotypic Test Results Reported?

When a genotypic testing report comes back from the lab, it contains a listing of the mutations that were found in the virus' reverse transcriptase and protease enzymes. It's important to understand how these mutations are reported.

An example: The M184V mutation is responsible for causing resistance to Epivir. The 184 refers to the amino acid position, or codon, in the reverse transcriptase enzyme. The M -- which stands for methionine -- is the amino acid at position 184 of a wild-type virus' reverse transcriptase enzyme. The V -- which stands for valine -- refers to the mutation that results in drug resistance. In other words, the amino acid methionine at position 184 has been replaced by a valine. This change prevents Epivir from binding with the enzyme to prevent the virus from reproducing.

While researchers have identified a number of mutations that can cause drug resistance, they don't know everything there is to know about these mutations. We know that some combinations of mutations cause the virus to become more resistant to antiretroviral drugs than other combinations of mutations. Researchers are still trying to determine which sequences of mutations are the most important.

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Some genetic mutations have yet to be fully identified by researchers. Such is the case with drugs like Videx and Zerit. In people who take these two drugs, resistance certainly does occur. However, researchers are only beginning to determine the exact genetic mutations that cause HIV to become less sensitive to these drugs.

Mutations known to cause resistance to Retrovir and Epivir can also be misleading. For example, a genotypic resistance test may show that a person's HIV has several genetic mutations that cause resistance to Retrovir. However, if the person is also taking Epivir -- which appears to increase HIV's sensitivity to Retrovir -- such genetic mutations may not accurately reflect the amount of Retrovir resistance.

Another limitation: genotypic tests do not evaluate the genetic structure of small HIV populations found in a blood sample. For example, there might be a population of HIV that contains a mutation at position M184V (the mutation that causes resistance to Epivir). Unless this particular strain accounts for more than 20% of the HIV population found in a blood sample, chances are that it will not be recognized by the test.




  
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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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