December 2006

• Genotypic Tests
• Interpreting Genotypic Test Results
• Phenotypic Tests
• Interpreting Phenotypic Test Results
• Virtual Phenotypic Tests

There are currently two basic types of resistance tests: genotypic and phenotypic tests. Experts recommend a genotypic test if you have recently been infected or have used only a few HIV medications. U.S. HIV treatment guidelines say that for people who have taken a large number of medications, it may be best to take both a genotypic and phenotypic test. Another option is to take what is called a "virtual phenotype," a type of genotypic test that gives you genotypic results and then plugs these results into a comprehensive database to provide results similar to a phenotypic test.

Keep in mind, however, that your doctor may be limited in the number and type of resistance tests he or she can order for you, depending on the clinic's policy and on how you pay for your treatment. Medicaid, private health insurance policies and state HIV/AIDS Drug Assistance Programs (ADAPs) may limit coverage to only a few tests a year and may even specify whether a genotypic, phenotypic or a virtual phenotypic test is allowed.

Genotypic Tests

With a genotypic test, a blood sample containing your HIV is examined to see if there are any mutations. The test results will pinpoint the exact HIV genes where the mutation or mutations occur. Once mutations are found, they are compared to a long list of mutations known to cause resistance to HIV medications.

This is the least expensive of all the resistance tests, costing about $350, and the results are usually available within two to three weeks. Genotypic tests are best used when only a few different mutations are expected. Your doctor, for instance, generally would not expect to see many mutations if you've never taken HIV medications before, or if you've only taken a few. But if you have been on many HIV treatment regimens or you are on a regimen containing protease inhibitors, the number of mutations may be high. In such cases, both a genotypic and phenotypic test are recommended.

Interpreting Genotypic Test Results

The challenge in resistance testing isn't spotting the HIV mutations -- it's figuring out what each mutation means. Just because you have a mutation does not necessarily mean you should switch HIV medications. It's much more complex than that, especially if you have many different HIV mutations.

For instance, for people with five or six mutations, the mutations may work together to make HIV partially -- or even completely -- resistant to a single medication or to an entire class of drugs. In other cases, a single mutation may make HIV resistant to one drug, but simultaneously make it more sensitive to another drug. As you can see, it can get complex. Plus, several companies make genotypic tests, with some variations in how each test works. However, the more experience a doctor and a laboratory have in using resistance tests, the more effectively they can interpret these tests. Deciding whether to switch medications because of resistance will depend on your treatment history and which treatment options are still available to you.

Phenotypic Tests

Phenotypic tests look for drug resistance in a completely different way from genotypic tests. Instead of finding specific mutations, they measure the ability of someone's HIV to reproduce in the presence of HIV medications.

To do this, blood samples containing your HIV are divided into many test tubes, each of which includes increasing doses of a given HIV medication. Laboratory technicians then carefully study the samples to see how your HIV reacts. By doing this, the lab workers can calculate how much of each HIV medication would be needed to keep your HIV from reproducing. The lab workers then compare these amounts to the amount of each drug needed to stop wild-type HIV from reproducing. As you can imagine, this test is more expensive than a genotypic test (it costs around $750 to $1,200) and results can take up to a month to get back.

Interpreting Phenotypic Test Results

Unlike genotypic tests, which spot specific HIV mutations known to confer resistance to medications, phenotypic tests try to measure how well the medications actually work on your virus. For instance, if a phenotypic test shows that the normal dose of AZT would have to be increased 15 times in order to stop your HIV from reproducing, we say it has "15-fold resistance." This would mean that your HIV is extremely resistant to AZT. But each drug and its fold change needs to be interpreted separately. A twofold increase in the amount of medication needed to stop HIV reproduction would be considered high resistance with some drugs, i.e., for tenofovir (Viread). For Kaletra (lopinavir/ritonavir), however, it means no resistance. (Note that if you have 15-fold resistance to AZT, this does not mean that the dose of AZT should be increased. Resistance tests are not currently used to determine doses of medications.)

It's your doctor's job to know how many "folds" of resistance your virus could have and still be treated effectively with a particular drug. Your doctor will also have to take into consideration how many HIV medications you've already been on, how successful each regimen was and the results of previous resistance tests.

Researchers are still studying how resistant HIV needs to be to make a medication completely ineffective, so your doctor might not be able to give you a definitive answer based on the results of a phenotypic test.

Another limit of phenotypic tests is that they only look at how your HIV reacts to one drug at a time. It's still a technical challenge to measure the effect of drug combinations. Most people on HIV treatment are taking three or more medications at the same time, which can make phenotypic test results a little less reliable. Phenotypic tests are particularly useful for unusual mutations, new medications and resistance to protease inhibitors.

Virtual Phenotypic Tests

A third type of resistance test is called a virtual phenotype. The virtual phenotypic test is, in many ways, a combination of a genotypic and a phenotypic test, but it costs $50 to $100 more than a genotype. Like a genotypic test, results are available within two to three weeks.

With this test, you can find out how likely it is that each of your mutations will be resistant to HIV medications -- which is exactly what a conventional phenotypic test finds, only you and your doctor don't have to actually get a phenotypic test. Plus, because the computer database used by this test is always updated with new test results from around the world, the results of a virtual phenotypic test are continually being refined and improved.

Interpreting Virtual Phenotypic Test Results

As you'll see from the sample test, once you take this test, you'll receive both a genotypic test result and a phenotypic analysis. In many ways, virtual phenotypic tests are just like conventional phenotypic tests: the amount of resistance is described in "fold changes," the results are easier to understand than genotypic test results and the test is ideal for people who have a complicated mix of mutations.

The virtual phenotypic test is different than a phenotypic test because your results are compared to hundreds of sample viruses with the same mutation, which may provide a more helpful prediction of the level of resistance than conventional phenotypic tests. A virtual phenotypic test, however, might not be as good as a conventional phenotypic test for figuring out whether your HIV is resistant to new medications. In addition, if you have any unusual HIV mutations, this test may have trouble figuring out whether they're drug resistant.

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