May 17, 2008
HIV mutates almost every time a new copy is made. Not every mutation causes resistance. The "wild type" virus is the most common form of HIV. Anything different from the wild type is considered a mutation.
An antitiviral drug won't control virus that is resistant to it. It can "escape" from the drug. If you keep taking the drug, the resistant virus will multiply the fastest. This is called "selective pressure."
If you stop taking medications, there is no selective pressure. The wild type virus will multiply the fastest. Although tests may not detect any drug resistance, it might come back if you re-start the same drugs.
Resistance testing helps doctors make better treatment decisions for their patients.
The more that HIV multiplies, the more mutations show up. These mutations happen by accident. The virus doesn't "figure out" which mutations will resist medications.
Just one mutation can make HIV resistant to some drugs. This is true for 3TC (Epivir) and the non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, HIV has to go through a series of mutations to develop resistance to other drugs, including most protease inhibitors.
The best way to prevent resistance is to control HIV by taking strong antiviral medications. If you miss doses of your medications, HIV will multiply more easily. More mutations will occur. Some of them could cause resistance.
If you have to stop taking any antiviral medication, talk to your doctor. You may have to stop some drugs sooner than others. If you stop taking drugs while the virus is under control, you should be able to use them again.
Clinical resistance shows up as a higher viral load, lower CD4 count, or opportunistic infections (see Fact Sheet 500). Laboratory tests can measure phenotypic and genotypic resistance.
Phenotypic resistance is reported as "fold" resistance. If the test sample grows twenty times as much as normal, it has "20-fold resistance."
Phenotypic tests cost about $800. It used to take over a month to get the results. New phenotypic tests are somewhat quicker.
Mutations are described by a combination of letters and numbers, for example K103N. The first letter (K) is the code for the amino acid in the wild type virus. The number (103) identifies the position of the codon. The second letter (N) is the code for the "changed" amino acid in the mutant sample.
Genotypic testing costs about $250. Results come back in about two weeks.
Cross-resistance is important when you change medications. You need to choose new drugs that are not cross-resistant to drugs you've already taken.
We do not totally understand cross-resistance. However, many drugs are at least partly cross-resistant. As HIV develops more mutations, it gets harder to control. Take every dose of your antiviral medications according to instructions. This reduces the risk of resistance and cross-resistance. It saves the most options for changing medications in the future.
The tests aren't good at detecting "minority" mutations (less than 20% of the virus population). Also, they work better when the viral load is higher. If your viral load is very low, the tests might not work.
Tests usually cannot be run if the patient's viral load is less than 500 to 1,000 copies per ml.
Test results can be difficult to understand. Drugs that should work according to the tests sometimes don't work, and vice versa. Sometimes genotypic and phenotypic tests give conflicting results for the same patient. Some mutations can "reverse" or reduce resistance to some medications.
Recent research suggests that a genotypic resistance test should be done for every patient before they start taking ARVs. This saves money by avoiding putting someone on ARVs that will not work for them.