Fact Sheet Number 414
- WHAT IS RESISTANCE?
- HOW DOES RESISTANCE DEVELOP?
- TYPES OF RESISTANCE
- PHENOTYPIC TESTING
- GENOTYPIC TESTING
- VIRTUAL PHENOTYPE
- CROSS RESISTANCE
- PROBLEMS WITH RESISTANCE TESTING
|
this Fact Sheet on a single page using: |
|
|
|
|
|
More information on Downloading & Printing Fact Sheets |
|
PrintHIV is “resistant” to a drug if it keeps multiplying
rapidly while you are taking the drug. Changes (mutations) in
the virus cause resistance. 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.
Antiviral drugs control most types of the virus. However, they
won’t control resistant virus. 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.
DEVELOP?
HIV usually becomes resistant when someone is taking drugs that
don’t totally control it. However, more people are getting infected
with HIV that is already resistant to one or more anti-HIV drugs.
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 us under
control, you should be able to use them again.
There are three types of resistance:
- Clinical resistance: HIV multiplies rapidly in your
body even though you’re taking antiviral drugs.
- Phenotypic resistance: HIV multiplies in a test tube
when antiviral drugs are added.
- Genotypic resistance: The genetic code of HIV has
mutations that are linked to drug resistance.
Laboratory tests can measure phenotypic and genotypic resistance.
A sample of HIV is grown in the laboratory. A dose of one antiviral
drug is added. The growth rate of the HIV is compared to the rate
of wild type virus. If the sample grows more than normal, it is
resistant to the medication.
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 quicker.
The genetic code of the sample virus is compared to the wild type.
The code is a long chain of molecules called nucleotides. Each
group of three nucleotides, called a “codon”, defines
a particular amino acid used to build a new virus.
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 mutant
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.
This test combines some elements of genotypic and phenotypic
testing. First, genotypic testing is done on the sample. Phenotypic
test results for other virus samples with a similar genotypic
pattern are taken from a database. These matched samples tell
you how the virus is likely to behave. The virtual phenotype is
faster and less expensive than a phenotypic test.
Sometimes a mutant version of HIV is resistant to more than one
drug. When this happens, the drugs are called “cross-resistant”.
For example, most HIV that is resistant to indinavir (Crixivan)
is also resistant to ritonavir (Norvir). This means that indinavir
and ritonavir are cross-resistant.
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.
RESISTANCE TESTING
Resistance tests are not available everywhere. They are expensive.
However, they are becoming more common, faster and cheaper.
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.
Test results can be difficult to understand. Sometimes they
don’t explain what actually happens with a patient. Drugs that
should work according to the tests sometimes don’t work, and vice
versa.
Despite these problems, many researchers believe that resistance
testing will become a normal part of HIV treatment in the next
several years. More physicians will probably use resistance testing
before choosing someone’s first antiviral medications to see if
they were infected by drug-resistant virus.
Revised July 26, 2002
Goto InfoNet Main Page
Go toIndex of Fact Sheets
Clickhere if you have questions
New Mexico AIDS Education and Training Center
and the New Mexico Department of Health