Genotypic and Phenotypic Resistance Tests -- What is the Difference?

HIV drug resistance occurs when the virus is able to resist the drugs ability to suppress or limit its reproduction. There are currently two tests used to measure for drug resistance. One kind of test is called a "genotypic" test, the other is called a "phenotypic" test. Resistance testing can be helpful for people who are just starting on medication and for people who have taken several different medications over a number of years and are experiencing viral rebound.

What is a "Genotypic" Test?
A genotypic test is a test that examines a specific person's HIV to see if the virus has mutations, and to determine where in the genetic structure of the virus those mutations occur. (Hence the name "genotypic".) Any mutations that are identified through this test are then compared with known drug resistant mutation points for all of the currently available HIV drugs. If there is a match between an identified mutation in the specific person's HIV and known drug-resistant mutation points, the virus is believed to be resistant to those drugs where there is a match.

Genotypic testing can be done in people with a viral load under 1,000 because genotypic testing only involves comparing a person's specific HIV mutations to known drug resistant mutation points. The test can be highly predictive of drug resistance for the "nucleoside analog" class of drugs (AZT, 3TC, ddI, etc.) and "non-nucleoside reverse transcriptase inhibitors" (Sustiva, Viramune, etc.) because these classes of drugs have fairly consistent mutation patterns. However, this test is less predictive of resistance patterns for "protease inhibitors" (Crixivan, Fortovase, etc.) since this class of drugs is not always consistent in the pattern of mutations it produces.

Genotypic testing is less expensive and much faster than phenotypic testing. Cost ranges from $300 to $500 per test, and results are usually available within a week. Insurance coverage varies from company to company, so check with your carrier for coverage verification. The data reported back can be very difficult to understand, even for physicians, so those unfamiliar with how to interpret the test may need to consult with a specialist in HIV care who is familiar with how to read and interpret the results.

What is a "Phenotypic" Test?
In a phenotypic test, a person's blood is divided into many test tubes. A different HIV drug is mixed into each test tube. The virus in each tube is then watched to see which drugs it is able to rapidly produce in the presence of. The amount of drug in each test tube is then increased until it is enough to stop virus reproduction. Based on the amount of drug necessary to stop viral reproduction, a resistance "profile" is created. A simplified way to think of the resistance profile for each drug is:
  1. Low-level resistance: when a 2 to 4 fold increase in the amount of drug in the test tube is needed to stop HIV reproduction.

  2. Some resistance: when a 4 to 10 fold increase in the amount of drug in the test tube is needed to stop HIV replication.

  3. High-level resistance: when a 10 fold increase or greater in the amount of drug in the test tube is needed to stop HIV replication.

Drugs which have a "low-level resistance" or "some resistance" may still work for the individual person as a part of combination therapy. Drugs which have a "high-level resistance" profile are believed to be ineffective in suppressing the virus, and increasing the dosage levels is not thought to be effective.

Phenotypic testing is generally most effective when a person's viral load is greater than 1,000. (For this reason, your provider may not do a phenotypic test if you have a viral load less than 1,000.) A downside to this test is that it does not measure how well different drugs work together in combination (and we know that some drugs can both increase or decrease how well other drugs work when used in combination with each other.) Phenotypic testing is very expensive, and costs about $1,000 each time the test is done. Also, it takes about 4 to 6 weeks to test a specific person's HIV against all the various drugs. As with genotypic testing, the results can be difficult to interpret and your provider may need to consult with an HIV specialist who knows how to read and interpret this test to make specific drug recommendations.