Resistance Testing

• Resistance -- How It Happens
• Genotypic and Phenotypic Tests
• When Should I Get a Resistance Test?
• Limitations
• The Future

Studies show that only half of the people who use HIV drug cocktails get full benefit from them. One reason is that HIV gets resistant to drugs. In other words, the virus becomes able to grow in spite of the drugs. Resistance testing is a new tool to help manage this problem. Everyone involved in HIV care needs to know how these tests work and when to use them.

Resistance -- How It Happens

HIV hijacks white blood cells, and uses them as factories to make more virus. To do this, the virus must first write instructions onto the cell on how to make HIV. The part of HIV that does the writing, called "reverse transcriptase" is very sloppy. It makes many errors and this ultimately results in many variations on the virus. Each variation is called a "mutant." There are about a million mutants made every day in untreated HIV infection.

Over time, some of these mutants will be resistant to our medicines. "Resistant" means the mutant can make more virus in spite of the drugs. The best way to make sure you don't get resistance is getting your viral load to zero, which may be lower than "undetectable." "Undetectable" means lower than the viral load test can measure. The closer to zero viral load gets, the longer it will take to get resistance.

Genotypic and Phenotypic Tests

There are two types of tests that analyze a person's HIV for resistance to medicines. One is called "genotypic" and the other is called "phenotypic."

Genotypic Tests:

When HIV becomes resistant to a drug, it has very specific changes in its genetic makeup. Scientists have kept track of these changes and can recognize them through genotypic tests. By recognizing these specific changes in genetic makeup, it is possible to identify which drugs are no longer effectively suppressing HIV.

Phenotypic Tests:

Another way to test whether a virus is resistant to a drug is to take some of the virus, put it in a test tube with samples of HIV drugs, and see if it grows well. If it grows, it is resistant to that drug. If it does not, it is "susceptible" to the drug. These types of tests are called phenotypic.

When Should I Get a Resistance Test?

Resistance tests are important to people at particular times in their HIV history. They are most useful at two points. First, if a cocktail does not get the virus down low enough when it is first used. Secondly, if the virus comes back after the cocktail has been effective for a long time. In both cases, resistance testing may be able to identify drugs the person has not yet used, to which the virus is not resistant.

Studies have shown that using resistance testing helps trained clinicians decide on what cocktails are best for a patient.

Limitations

Testing for resistance is in early development. Resistance testing is growing in sophistication and someday may be a cornerstone to effective therapy. Presently, resistance tests are useful under the following conditions:

1. Your viral load is over 500 RNA copies

2. The test is good for the particular drug being tested. (At this stage the tests have difficulty determining resistance for certain drugs, like D4T for example.)

3. At least 20% of your virus is resistant to the drug being tested.

4. You understand that right now, the tests can only test one drug at a time. (Many of us are on cocktails. Just because a test says a virus is resistant to a certain drug it doesn't mean that the virus is necessarily resistant to a combination of drugs used in a cocktail.)

5. You have a doctor very experienced in interpreting these tests.

6. You are not considering new drugs based on new principles, like the "fusion inhibitors," which have not been around long enough to get good information on resistance patterns. (It is important to check with the test company to find out the latest news on which drugs the company is able to test for.)

The Future

Scientists are working on making these tests better. They are developing more sensitive tests that can search for resistance with a smaller amount of virus. Someday, the tests will be able to look at virus below 50 copies. This would allow us to know if a drug we are taking is going to fail in the near future. Scientists are also trying to create tests to analyze not just single drug therapies but drug combinations.

Until then, use resistance tests when it makes sense -- when your regimen is not doing what it should.

Today, if your present drug therapy fails, resistance testing will help identify what additional drugs might not work on your virus before you start taking them. Tomorrow, it will help you plan your changes in therapy before the drugs fail.

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David Scondras is the founder and chairman of Search For A Cure. Scondras developed the nationally recognized HIV treatment series, Reasons for Hope. All articles in the series are reviewed by expert HIV doctors, scientists, and an HIV positive and negative focus group to ensure both accuracy and understandability.

This article was reviewed by Dr. Richard D'Aquila, Infectious Disease Division, Massachusetts General Hospital and Professor of Medicine, Harvard University.

If you have any questions or would like to receive the Reasons For Hope series, contact Search For A Cure at 34 Edgerly Road #1, Boston, MA 02115 or call 617-536-2474, fax 617-266-0051, or send e-mail to hope@sfac.org. Visit our Web site at www.searchforacure.org.

Search For A Cure is a not for profit organization providing education, promoting access and advocating the basic human right to safe and effective treatment for all people living with AIDS.