Appendix E: Drug Resistance and Resistance Testing
Part of A Practical Guide to HIV Drug Treatment for People Living With HIV
This appendix looks at how HIV can develop resistance to antiretroviral drugs and how labs test for drug resistance.
At the base of drug resistance is the fact that HIV is a little sloppy about making copies of itself. The new copies often contain changes, called mutations. These small changes in the genetic material of the virus result in changes to the way the virus is put together. Some mutations may allow the virus to replicate even when antiretroviral drugs are being used. This ability to replicate in the presence of antiretroviral drugs is called drug resistance.
If the HIV in your body becomes resistant to one or more drugs, those drugs won't work anymore. If you keep taking those medications, they won't stop HIV from replicating and infecting cells in your body. Your viral load will increase and the damage to your body and immune system will increase. This situation is called treatment failure. To get HIV back under control, you and your doctor will likely switch your drug combination, but because you can't re-use a drug the virus is resistant to, you will have fewer options to choose from. (See "Changing Medications Due to Treatment Failure" for a discussion of treatment failure.)
Resistance to one drug can cause cross-resistance to other drugs in the same class, even if you haven't taken those other drugs before. (For instance, most non-nukes are highly cross-resistant: if you are resistant to nevirapine, you'll probably also be resistant to efavirenz, and vice versa.)
It is possible to become infected with a strain of HIV that is already resistant to certain drugs. Drug resistance can also happen when you end up with a small amount of drug in the body but not enough to fully suppress the virus. This can happen as a result of missing doses or not taking your antiretroviral drugs regularly. If you're taking enough of a drug consistently, resistance is highly unlikely. It's that middle ground -- when you're taking a drug, but not enough of it -- that can lead to resistance. That's why it's so important to take your meds regularly and on schedule; this is called adherence. (See "Making Your Treatment Work Long-Term" for tips and tricks to sticking to your medication schedule.)
It is possible to do a blood test to check whether your HIV is resistant to any drugs. These tests may be useful in two situations:
In either case, it makes sense to check whether you have virus that is resistant to any anti-HIV drugs and, if so, which ones. In Canada, genotypic tests are routinely used to identify drug resistance. Genotypic tests identify specific mutations in the virus that can lead to resistance to a particular drug.
There is another type of test called a phenotypic test, which measures the amount of drug needed to de-activate a sample of virus: the more drug that is needed, the more resistant the virus is. Phenotypic tests are not commonly used because they are considerably more difficult to run and few labs offer them. Phenotypic tests also take a lot longer to do than genotypic tests and are significantly more costly. There is no evidence to suggest that either type of test provides better results.
Both the genotypic and phenotypic tests have limitations. If you only have a small amount of virus that is resistant to a drug, the test may not detect it. As a result, the tests will be able to accurately tell you which drugs will not work for you, but they will not be able to say with certainty which drugs will work.
Resistance test results are complex and are best interpreted by an HIV doctor with a good deal of experience working with viral resistance. In the right hands, and combined with a knowledge of which antiretroviral drugs you've already taken, resistance testing can be an extremely useful tool for figuring out which drugs will work best for you.
For more information, see "Resistance Assistance" in the Fall/Winter 2005 issue of The Positive Side (www.positiveside.ca).
How HIV Drug Resistance Develops: A Visual Story
Part One: HIV Is a Weed; Treatment Stops the Weed From Growing
Part Two: Missing Doses Allows the Weed to Grow
This article was provided by Canadian AIDS Treatment Information Exchange. Visit CATIE's Web site to find out more about their activities, publications and services.
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