This Factsheet provides basic information on tests designed to measure resistance to anti-HIV drugs.To learn more about resistance see NAM Factsheet :Resistance.  

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, particularly now that the British HIV Association advises that tests should be used whenever an anti-HIV drug combination is changed, and you should ask if a resistance test is being performed if you are unsure.

Resistance tests are fairly expensive and producing results takes time. They are hard to perform and interpret; standardisation and quality control are lacking; they can’t be done at viral load levels below 200.

On the other hand, people who change therapy knowing the results of a resistance test are more likely to have a successful viral load response to their new treatment, at least over the short-term, than people who switch without this information.

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 4-5 days; they are cheaper than phenotypic tests, at around £200 per test; 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.

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 2-3 weeks; they are more expensive, around £400-600 per test; they employ complex lab equipment; and  they cannot be done at viral load levels below 200 copies.

Guidance on resistance tests

• Resistance tests are a new development in HIV care, and so results should be interpreted and explained by someone who is experienced in using them.

• 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; missed doses, poor absorption and drug interactions are other possible causes to consider.

• Resistance tests cannot be done if your viral load is below 200 copies.

• 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 10-20% 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 anti-HIV treatment. If you were infected with HIV which is resistant to one of the drugs in your first combination, your treatment may fail quickly. However, the use of resistance tests carried out before starting treatment is even less well understood than in people who are changing combinations. In these circumstances, tests might only detect resistant viruses which persist long after infection, e.g. AZT resistance. Over time however, the viral population evolves; resistant viruses may form only a small minority of the total population. This means they may be undetectable before you start treatment, at which point they could increase rapidly.

• 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 anti-HIV treatment and whenever treatment is changed.