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 Antiretroviral Drug Resistance Testing, Genotypic
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 an individual is resistant or has developed resistance to one or more antiretroviral therapy (ART) drugs. The test analyzes the genes of the HIV strain infecting the person to identify mutations that may cause the virus to be resistant to ART. Someone may be initially infected with a drug-resistant HIV strain or drug resistance may develop during treatment.
In general, drug resistance describes the condition in which a microorganism 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 microorganism's genes. This change leads to a mixed population in the infected person's body – some microorganisms that are drug-resistant and some that are drug-sensitive. Microorganisms 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 proliferation of the genetic forms of the microorganism that are resistant to it. When this occurs, the antimicrobial is no longer effective in treating the infection.
HIV mutates frequently – even in the absence of drug treatment – but not every mutation causes resistance to antiretroviral drugs. With genotypic resistance testing, the genetic code of the HIV a person has 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 Allergy and Infectious Diseases web page on Treatment of HIV Infection.
How is it used?
HIV genotypic antiretroviral resistance testing is used to help select a drug regimen that will likely be effective in treating a person with an HIV infection. The test is used to determine whether the HIV strain infecting an individual 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.
ART is intended to suppress the amount of virus (viral load) in order to decrease the risk of the disease progression and to minimize viral replication and mutation. However, a person 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.
When a person is 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 a person begins treatment to help determine the cause of drug treatment failure. Treatment failure is identified when a person's viral load does not decrease or begins to increase despite treatment. In this case, the person's 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
To avoid the development of ART resistance, individuals with HIV are usually treated with a combination of drugs that are from two different classes of ART. This is known as highly active antiretroviral therapy or HAART. (For more, see the "What is being tested?" section.)
When is it ordered?
HIV genotypic resistance testing is recommended when a person is first diagnosed with an HIV infection and before initiating therapy. If treatment is not initiated soon after diagnosis, then repeat resistance testing should be considered prior to the start of therapy.
Testing may also be ordered when HIV viral load values do not decrease or rise steadily during therapy, indicating that HIV may be developing resistance. Generally, a treatment is considered a failure if a viral load rises more than three-fold in consecutive tests. If drug resistance is found, a new treatment regimen may be chosen.
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 the test and selecting appropriate ART.
The test results identify the viral mutations detected. These are described by a combination of letters and numbers (for example, K103N) where the letters refer to the amino acid associated with the gene and the number refers to the position of the mutation in the genome.
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 the patient's HIV.
Is there anything else I should know?
HIV resistance testing is not recommended if a person's 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.
HIV genotypic resistance is a qualitative test and detects mutations associated with drug resistance. It does not report the level of resistance associated with the drug. Phenotypic resistance testing (see Common Questions #2) is a better indicator of the level of HIV drug resistance.
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.
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 ARV, 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.
On This Site
Conditions: HIV Infection and AIDS
Elsewhere On The Web
AIDS.gov: Drug Resistance
AIDS InfoNet: HIV Resistance Testing
AIDSinfo.gov: FDA-Approved HIV Medicines
National Institute on Allergy and Infectious Diseases: Types of HIV/AIDs Antiretroviral Drugs
MedlinePlus Medical Encyclopedia: HIV/AIDS Medicines
Centers for Disease Control and Prevention: HIV Treatment