HIV Genotypic Resistance Testing

If you are infected with HIV, genotypic resistance testing is used to detect the presence of one or more mutations in the virus causing your infection that enable it to be resistant to certain anti-retroviral drugs (ARVs). The mutations will specify the drugs to which the virus is resistant. Your doctor will then be able to select a treatment that will be effective. Genotypic testing helps your doctor make better treatment decisions when considering which drugs to use before beginning therapy or when the ARV you are taking is not working effectively.

HIV genotypic resistance testing may be ordered when you are first diagnosed to determine whether you are infected with a strain of HIV that is known to be resistant to certain ARV regardless of whether you will begin treatment right away. It may also be ordered immediately before the start of therapy if a drug-resistant virus is suspected, so that immediate, appropriate therapy is possible. Testing may also be ordered when viral load values (a measure of how much HIV is in your body) rise steadily during therapy, indicating treatment failure and the possibility of resistance. Generally, a treatment is considered a failure if your viral load rises more than three-fold in consecutive tests. If drug resistance is found, a new treatment regimen may be chosen.

Genotypic resistance testing should be performed on all HIV-positive pregnant women prior to starting therapy and for those women who become pregnant while on ARV and who have detectable viral loads.

Results of genotypic resistance testing must be interpreted with caution. Often, a specialist is consulted when considering results of the test and selecting appropriate ARV. The test results identify the viral mutations. 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. Based on the test result, your doctor will determine whether a given mutation is one known to cause drug resistance. Not all mutations cause drug resistance. Some mutations are very common, and resistance is known to certain drugs and/or drug combinations. This is important information for your doctor to help predict which treatment regimen will work best for you. The International AIDS Society—USA maintains a list of primary and secondary mutations that are most commonly associated with resistance to various ARVs and ARV categories. The list is intended to help interpret the results of resistance testing and in selecting appropriate ARV therapy.

Genotypic resistance testing is not recommended if your viral load is less than 500 copies/mL. There is insufficient amount of HIV RNA for testing to be reliable. Testing works best if the viral load is greater than 1,000 copies/mL but 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 give you the level of resistance associated with the drug. Phenotypic resistance testing 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 various strains of HIV. The test may not detect a drug-resistant strain of HIV if the resistant virus makes up less than 10-20% of total virus that is present 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.