Resistance -- How It HappensHIV 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 TestsThere 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.
LimitationsTesting 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:
The FutureScientists 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.
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.
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This article was provided by Search for a Cure. It is a part of the publication Reasons for Hope.