If you have been diagnosed with human immunodeficiency virus (HIV), to determine whether the strain causing your infection is resistant or has developed resistance to one or more antiretroviral therapy (ART) drugs
HIV Drug Resistance Testing, Genotype
When first diagnosed with HIV, immediately prior to the start of antiretroviral therapy, or when you are receiving ART but the amount of virus in your blood (HIV viral load) does not decrease or rises steadily
A blood sample drawn from a vein in your arm
Human immunodeficiency virus (HIV) genotypic antiretroviral drug resistance testing evaluates the likelihood that the HIV strain infecting you is resistant or has developed resistance to one or more antiretroviral therapy (ART) drugs. The test analyzes the genes of the HIV strain infecting you to identify mutations that may cause the virus to be resistant to ART.
ART is intended to suppress the amount of HIV virus (viral load) in order to decrease the risk of the disease progressing. However, you may be initially infected with a drug-resistant HIV strain or drug resistance may develop during treatment, causing ART to be ineffective in suppressing the virus.
In general, drug resistance describes the condition in which a microbe (e.g., virus, bacteria) is able to survive, grow and/or multiply in the presence of one or more antimicrobial drugs. Resistance can develop when antimicrobials are used to treat an infection and a mutation or change occurs in one of the microbe's genes. This change leads to a mixed population in your body – some microbes that are drug-resistant and some that are drug-sensitive. Microbes without the mutation are killed, but those that have the mutation quickly multiply and begin to predominate. This is called "selective pressure" because the drug "selects" and allows the growth of the microbes that are resistant to it. When this occurs, the antimicrobial is no longer effective in treating your infection.
HIV mutates frequently – even in the absence of drug treatment – but not every mutation causes resistance to ART. With genotypic resistance testing, the genetic code of the HIV you have been infected with is analyzed to determine if there are any genetic mutations that are known to cause ART resistance.
To avoid the development of ART resistance, it is recommended that individuals with HIV be treated with a combination of drugs that are from two different classes of antiretroviral drugs. This is known as highly active antiretroviral therapy or HAART. There are many different antiretroviral drugs approved by the U.S. Food and Drug Administration. For more on this, visit the National Institute of Health's web page on FDA-Approved HIV Medicines.
How is the test used?
HIV genotypic antiretroviral resistance testing is used to help select a drug regimen that will likely be effective in treating your HIV infection. The test is used to determine whether the HIV strain infecting you is resistant or has developed resistance to one or more drugs used to treat HIV. Testing analyzes the genes of the virus to detect the presence of one or more mutations that are associated with antiretroviral drug (ART) resistance.
- When you are first diagnosed, HIV drug resistance testing is used to determine whether the HIV strain is already resistant to one or more drugs. The information is used to identify and select the antiretroviral drugs that will likely be effective.
- Testing may also be used after you begin treatment to help determine the cause of drug treatment failure. Treatment failure is identified when your HIV viral load does not decrease or begins to increase despite treatment. In this case, your treatment will likely be changed. Results of antiretroviral resistance testing may help select a different drug regimen that may be effective in suppressing the virus.
Testing is used to identify resistance to antiretroviral drugs in classes such as:
- Protease inhibitors
- Reverse transcriptase inhibitors
- Integrase inhibitors
When is it ordered?
HIV genotypic resistance testing is recommended when you are first diagnosed with an HIV infection and before starting therapy. If treatment is not started soon after diagnosis, then it is recommended that resistance testing be repeated before starting therapy.
Testing may also be ordered when your HIV viral load values do not decrease or they rise steadily during therapy, indicating that your HIV may be developing resistance. Generally, your treatment is considered a failure if your viral load rises more than three-fold in consecutive tests.
What does the test result mean?
In general, the mutations detected by the test indicate the drugs to which the HIV strain is likely to be resistant. However, not all mutations cause drug resistance and the results of genotypic resistance testing must be interpreted with caution. A specialist may be consulted when considering results of your test and selecting appropriate ART.
The test results identify the HIV viral mutations detected. These are described by a combination of letters and numbers where the letters refer to the amino acid associated with the HIV gene and the number refers to the position of the mutation in the HIV's genome. For example, the mutation K103N may be detected. K is the amino acid and 103 is the position of the mutation.
The laboratory report may also provide an interpretation and a list of the drugs to which the virus is either resistant or susceptible. This information helps a healthcare practitioner select a treatment regimen that is likely to be effective in suppressing your HIV. If you are being treated with ART and the test results indicate that the HIV strain has become resistant to it, you will likely be switched to a new treatment regimen.
How long will it take to get the results of my test?
What is HIV phenotypic resistance testing?
HIV phenotypic resistance testing is the same as genotypic testing in that it tests the strain of HIV causing your infection for resistance to specific ART, but it uses a different method. In the lab, a sample of the virus grown in culture is mixed with different concentrations of one or more drugs. If the virus is able to replicate in the presence of the drug, as compared to a known strain of virus (a reference virus), it is said to be resistant to that drug. This type of testing usually takes longer than genotypic resistance testing.
HIV genotypic resistance detects mutations associated with drug resistance. It does not report the level of resistance associated with the drug. Phenotypic resistance testing is a better indicator of the level of HIV drug resistance than genotypic testing.
My healthcare practitioner says my viral load is too low for drug resistance testing. Why?
HIV drug resistance testing is not recommended if your viral load is less than 500 copies/mL. In this case, there is insufficient amount of HIV genetic material (RNA) for testing to be reliable. Testing works best if the viral load is greater than 1,000 copies/mL, but testing is recommended even if the level is between 500 and 1,000 copies/mL.
Is there anything else I should know?
HIV genotypic resistance testing cannot detect unknown resistance mutations that may be present in rare strains of HIV. The test may not detect a drug-resistant strain of HIV if the resistant gene is only present in less than 10-20% of total virus that is circulating in the blood.
Testing is not recommended after discontinuing a drug. This is because the percentage of drug-resistant strain may decrease considerably in the absence of the drug. When "selective pressure" from a drug is absent, the drug-resistant strain may drop enough to the point where testing would not be able to detect it. Because of this, if testing is performed to evaluate a failed treatment, it should be done while a person is taking the drugs, or if this is not possible, then within 4 weeks of stopping therapy.