Resistance tests

This Factsheet provides basic information on tests designed to measure resistance to anti-HIV drugs.

Resistance testing has been used in HIV research for some time to increase our knowledge of how resistance to anti-HIV drugs develops. It is also being used in clinics to inform treatment decisions, and the British HIV Association (the professional body of UK HIV doctors) advises that tests should be used whenever an anti-HIV drug combination is started or changed.

Your HIV clinic will take a blood sample  to be tested for resistance. This sample will be sent for specialist analysis. The results of resistance tests are not accurate if your viral load is below 200 copies/ml.

Types of resistance test

There are two methods of testing for drug resistance:

• genotypic tests which look for specific changes, or mutations, in HIV’s reverse transcriptase or protease genes that are linked to resistance to anti-HIV drugs.

• phenotypic tests which measure the concentration of a drug required to reduce viral replication. When resistance to a drug begins to develop, higher levels of that drug will be needed to stop the virus growing.

There is no clear indication that one type of test is more useful than the other at present. Each has its pros and cons.

Genotypic tests

The advantages of genotypic tests are that results are available relatively quickly, in four to five days; they are cheaper than phenotypic tests; they employ relatively simple technology; they don’t require highly skilled staff; and they are predictive – genotypic changes occur before phenotypic changes. The disadvantages are that they provide an indirect measure of resistance; they require complex interpretation; they cannot be done at viral load levels below 200 copies/ml.

Phenotypic tests

The advantages of phenotypic tests are that they directly measure the sensitivity of the virus to a drug, and that they are relatively easy to interpret. The disadvantages are that they are slow to turn around, requiring two to three weeks; they are more expensive; they employ complex lab equipment; and they cannot be done at viral load levels below 200 copies/ml.

Guidance on resistance tests

• Test results should be considered alongside a full treatment and care history, rather than in isolation.
• Resistance is not the only reason why drugs fail; adherence, poor absorption and drug interactions are other possible causes to consider.
• Resistance tests cannot be done if your viral load is below 200 copies/ml.
• Resistance tests will be more accurate if performed while you are still taking a failing combination rather than after you have stopped it. This is because when you stop your current drugs, resistant viruses will usually be less likely to reproduce than sensitive viruses. Resistant viruses that once predominated will then grow alongside sensitive viruses until they form one of many sub-groups of viruses within your body. Most tests are unable to spot resistant sub-groups which form less than 10 to 20% of your viral population. Restarting a drug to which a pool of viruses are resistant will allow this group to grow again, causing the treatment to fail.
• One of the most important times to test for resistance could be before you start HIV treatment. If you were infected with HIV that is resistant to one of the drugs in your first combination, your treatment may fail quickly.
• Resistance testing may be helpful in guiding treatment choices in people very recently infected however, because resistant viruses will not have disappeared at this point.
• UK treatment guidelines advise that resistance tests should be used before you start HIV treatment and whenever treatment is changed.