Also known as: antiretroviral drug resistance test; ARV resistance test
Name: Human immunodeficiency virus genotypic resistance test
Related tests: Viral load
At a glanceThe testTest infoFAQ
Why is the test done?
If you have been diagnosed with HIV and are on antiretroviral treatment, or if the treatment you are on has not been effective.
When is the test done?
When HIV is first diagnosed and/or just before starting antiretroviral treatment, or if HIV viral load levels are rising steadily despite antiretroviral treatment.
What samples are required?
A blood sample taken from a vein in the arm
Is any preparation needed for the test?
None
How is it tested?
Resistance is a term used to describe the situation in which a microorganism can grow and/or multiply in the presence of one or more antimicrobial medicines. Sometimes, when antimicrobials are used to treat an infection, a mutation or change occurs in one of the genes of the microorganism causing the infection. The mutation can allow the microorganism to develop resistance, i.e. to grow and multiply despite the presence of the antimicrobial medicine. Microorganisms without the mutation die, while those with the mutation multiply rapidly and become predominant. At this point the antimicrobial is no longer effective in treating the infection. In HIV infection, mutations in viral genes can occur during treatment, allowing the virus to replicate and develop resistance to antiretroviral drugs (ARVs). A person may also be infected with a strain of HIV that is already resistant to some drugs. In some cases the resistance test can give the doctor information even before treatment starts.
There are a few different methods that can be used to determine whether HIV is resistant to an antiretroviral drug. If you have HIV and are currently on antiretroviral treatment but your viral load continues to rise, a phenotypic or genotypic resistance test may be requested. In the genotypic resistance test, the genetic code of the HIV you are infected with is examined in detail to look for certain gene mutations, or variations, that are known to cause drug resistance. HIV mutates almost every time it replicates to produce a new copy, but not all mutations can cause resistance. At any time there is always more than one genetic form of the virus (drug-resistant and drug-sensitive), and all the genetically different viruses can multiply at the same time in a patient. In the presence of the drug, however, the resistant population will come to clearly outnumber the drug-sensitive one. This is called “selective pressure”, because the drug “selects” the genetic form of the virus that is resistant to it.
To prevent ARV resistance from developing, treatment with a combination of drugs from two different ARV classes is generally recommended. This is known as highly active antiretroviral therapy, or HAART. There are several antiretrovirals approved by the US Food and Drug Administration belonging to different classes. Many of them are listed on the National Institute of Allergy and Infectious Diseases website under Treatment of HIV Infection.
How is the sample collected for testing?
The sample is a simple blood sample from a vein in the arm. The genotypic resistance test works on blood samples with a viral load of at least 1,000 copies per mL of blood. If the viral load is very low, the test may not work and may not detect resistance to all antiretrovirals. The test is therefore recommended for people with a viral load between 500 and 1,000 copies/mL
Is any preparation needed to ensure the quality of the sample?
No preparation is needed for the test.
1. How is it used?
2. When is it requested?
3. What does the result mean?
4. Is there anything else I should know?
1. How is it used?
If you have HIV, the genotypic resistance test is used to detect one or more mutations in the genome of the virus causing the infection that may have made it resistant to some antiretroviral drugs. Identifying the type of mutation present also identifies the drugs to which the virus is resistant. The doctor will then be able to choose a treatment that is likely to be effective. The genotypic test helps the doctor give the best treatment when choosing which drug to use and before starting a new treatment if the previous one has failed.
2. When is it requested?
The HIV genotypic resistance test may be requested at the first diagnosis, to determine whether the infection is actually with a strain of HIV known to be resistant to some antiretrovirals, whether or not the patient starts treatment immediately or later.
It may also be requested before starting treatment if a drug-resistant virus is suspected, so that appropriate treatment can be planned. The test may also be requested when viral load values (a measure of how much HIV is present in the body) rise steadily despite treatment, indicating that treatment is failing and that resistance is likely. Treatment is generally considered to have failed if the viral load rises more than three-fold in consecutive tests. If drug resistance is found, a new treatment can be chosen.
The genotypic resistance test should be carried out, before starting treatment, in all HIV-positive pregnant women and in women who become pregnant during antiretroviral treatment when their viral load is detectable.
3. What does the result mean?
Genotypic resistance test results must be interpreted with caution. A specialist should often be consulted to assess the test result and choose an appropriate antiretroviral. The test shows which viral mutations are present; these are represented by a combination of letters and numbers (for example K103N), where the letters refer to the amino acids involved and the numbers to the position of the mutation in the genome. Based on the test result, the doctor will assess whether the mutation identified is known to cause drug resistance. Not all mutations cause resistance to antiretrovirals; some are very common, and it is known which drug and/or combination of drugs they cause resistance to. This is important information for the doctor, allowing them to choose the treatment that is likely to give the best results. The International AIDS Society-USA maintains a list of the primary and secondary mutations most commonly associated with resistance to various antiretrovirals and classes of antiretroviral. The list is intended to help interpret resistance test results and choose appropriate treatment.
4. Is there anything else I should know?
The genotypic resistance test is not recommended if the viral load is below 500 copies/mL, as there is not enough HIV RNA for the test to be reliable. The test works well if the viral load is above 1,000 copies/mL, but it is also recommended if the level is between 500 and 1,000 copies/mL.
HIV genotypic resistance is a qualitative test that detects mutations associated with drug resistance. It does not, however, show the level of drug resistance. The phenotypic resistance test is a better indicator of the level of HIV drug resistance. The genotypic resistance test cannot detect unknown mutations that may be present in various strains of HIV. The test may not detect a resistant strain of HIV if it makes up less than 10-20% of the total virus in the blood.
The test is not recommended after a drug has been stopped, because the proportion of the drug-resistant strain can fall considerably in the absence of the drug. When the drug’s “selective pressure” is absent, the drug-resistant strain can fall enough for the test to miss it
1. How long does it take to get the test results?
2. What is the HIV phenotypic resistance test?
1. How long does it take to get the test results?
It depends on where it is done; the sample may be sent to a reference laboratory. Results can be available within one or two weeks.
2. What is the HIV phenotypic resistance test?
The HIV phenotypic resistance test uses a different method but, like the genotypic resistance test, shows whether the strain of HIV causing the infection is resistant to specific antiretroviral drugs. In the laboratory, a sample of virus grown in culture is mixed with different concentrations of one or more drugs. If the virus can replicate in the presence of the antiretroviral, compared with a known strain of virus (reference virus), it can be said to be resistant to the drug. This type of test generally takes longer than the genotypic resistance test.