5.1 Recap of previous section
The previous section looked at how resistance is measured and how test results are interpreted.
- There are three main types of resistance tests but genotype tests are used most often. Genotype tests report mutations (ie M184V) and phenotype test report fold-changes (ie 4-fold resistance). All tests should include a detailed interpretation of the results – ie whether each drug is likely to be active (sensitive), partially active (reduced sensitivity) or inactive (resistant).
- Different mutations have different clinical implications: some are associated with high level resistance and some with lower resistance. Resistance to a drug usually occurs on a progressive scale.
- Resistance to one drug in a class often means you have resistance to similar drugs in the same class. This is called cross-resistance.
- Resistance can only be tested when viral load is detectable but different labs have different lower viral load cut-offs for the test to work.
- When deciding on treatment, it is important to consider the whole history of resistance. This include previous treatment history and previous resistance tests, not just the results of the current resistance test. The interpretation of complicated results requires expert advice.
5.2 Introduction to section 5
In this section we look at when resistance tests should be used based on treatment guidelines.
- UK recommendations are based on BHIVA guidelines (see the monitoring guidelines, adult guidelines, and pregnancy guidelines) and PENTA (paediatric guidelines).
Other guidelines include:
- European HIV Drug Resistance Guidelines (2009) – download PDF (120 Kb)
- US treatment guidelines (DHHS)
Most treatment guidelines for Western countries have similar recommendations for resistance testing. The resistance section of the BHIVA adult guidelines is summarised in Appendix 8.
Section 5 also includes access to resistance testing.
- Why are these tests not always given?
- When to advocate for someone who has not been given a test
5.3 When to use resistance tests
Genotype resistance tests are recommended when first diagnosed and before most treatment changes (see Table 3), including:
- When first diagnosed (to check for transmitted drug resistance).
- Before starting treatment (to help with the choice of treatment) if someone has never had a resistance test or if they have been at risk of reinfection since the first resistance test.
- Before any change of treatment, as long as viral load is detectable.
Table 3: When to use resistance tests
|Newly diagnosed||Yes, all patients. Both for recent infection (less than 6 months) and chronic (longer than 6 months) infection.||In the UK, 5-15% of newly diagnosed people have at least one major mutation to at least one drug class.|
|Starting first treatment||Yes, BEFORE STARTING treatment.i) People who have never had a resistance test should have a sample tested before starting treatment.ii) People who may have been reinfected with a new strain of HIV since their first resistance test may be retested before starting treatment.||i) For people who have never been tested, then testing the earliest stored sample is recommended. If this is not available, then a current sample should be used. ii) Reinfection is well documented, though how often this happens is not known. If someone has had other exposures since diagnosis (from not using condoms with other positive partners), a resistance test will help limit the chance that their first treatment will fail, especially an NNRTI is included in the combination.|
|Changing treatment (viral failure)||Yes. If viral load has rebounded when on treatment, resistance should be tested BEFORE CHANGING treatment. Viral load needs to be detectable for the test to work, and the level needed varies by lab. Resistance testing can help determine if treatment failure is due to reinfection (superinfection) with a new strain of HIV.||A resistance test BEFORE CHANGING treatment will provide an indication of how much resistance developed while the treatment was failing. Some low level resistance may not be detected.|
|Changing treatment (side effects)||No. If you are just changing treatment due to side effects and your viral load is undetectable, resistance testing is not needed. If this is soon after starting treatment and viral load is still reducing, resistance testing is not needed.||Resistance only develops on failing treatment. Never test when viral load is undetectable. Check with lab for levels needed.|
|Pregnancy||Women who start treatment during pregnancy should be tested for drug resistance. Resistance testing should be done if viral load is still detectable at delivery. If the women chooses to stop treatment after the birth, resistance should be tested six weeks after stopping treatment.||As for ‘Starting Treatment’.Testing if viral load remains detectable is important for future care. Although treatment should be stopped carefully to reduce the risk of resistance, this should be confirmed with a resistance test.|
|Children||Guidelines for resistance testing in children are the same as for adults.In the rare cases (in Western countries) of infants born with HIV, resistance testing should be included with the full panel of other tests. Resistance in these circumstances is common.||Resistance develops in children in the same way as it does in adults. Any child on treatment with a detectable viral load is likely to have developed, or be developing resistance.|
|Before using a CCR5 inhibitor (ie maraviroc)||UK and European guidelines recommend using type of genotype test to check viral tropism.||CCR5 inhibitor only work against CCR5-tropic virus.|
|PEP (Post-Exposure Prophylaxis)||PEP should be started as soon as possible. It should not be delayed waiting for resistance test results.If the HIV-positive partner has drug resistance, this will affect the choice of drugs used for PEP. If resistance is discovered later the drugs can be modified.||PEP combinations usually include protease inhibitors as transmitted PI resistance is less common.The urgency with PEP is to first start any combination.|
5.4 Which tests to use: genotype or phenotype?
Recommendations for resistance testing always refer to GENOTYPE tests first.
This is because genotype tests are cheaper (approximately £200 vs £700) and quicker (1–2 weeks compared to more than two weeks), compared to phenotype tests. Genotype results are also more widely understood.
A phenotype test is generally only recommended if the results from a genotype test are difficult to interpret.
Phenotype tests (including virtual phenotype tests) are only used in people who have very limited treatment choices. This is usually in a case where there is extensive resistance to several different classes of HIV drugs.
Question: Are resistance tests used to see if the type of HIV in different people is in some way linked – in prosecution cases of transmission, for example?
Answer: No. The tests comparing two different viruses are called phylogenetic tests. They are more complicated and expensive tests. It is important to remember that phylogenetic tests can show when people have a similar virus, but not the direction of infection (ie whether one partner infected another).
5.5 How to access tests if the guidelines are not followed
Although guidelines are clear on the importance of resistance tests, they are not always provided routinely in all clinics. This is why it is important to know about the current UK guidelines.
If this is for cost reasons, then it is important to go back to the clinic to ensure that the test is included as part of current standard of care.
For example, we commonly hear that newly diagnosed people do not always get resistance tests.
- Usually it is sufficient to go back to your doctor and refer to the UK guidelines.
- Some clinics store a sample to test later, before starting treatment. In theory this may be okay, but sometimes samples get lost, or old samples may be difficult to test. In these cases, testing the current sample may not pick up resistance which is present at low levels. There is no real cost-saving from delaying this test.
- If your doctor or clinic will not agree to the test when it is clearly recommended, you can write to the head of your clinic and the head of your health trust. If this is still not provided you may want to register at another clinic to get this test. You can always change back to your local clinic in the future for routine monitoring or treatment.
Please call the i-Base phoneline if you would like further information or support in accessing resistance tests.
5.6 Section 5: Learning points
This section has been more practical and should help connect the previous technical information to how this affects things in the clinic.
- Treatment guidelines are an important resource, because they state when tests should be used. Most guidelines agree on the use of resistance testing. Guidelines are free to access online.
- Genotype tests are used routinely. Phenotype tests are used when there is more complicated resistance and fewer treatment options. They are used when the genotype results are unclear.
- Guidelines are not always followed, especially for newly diagnosed people.
- Resistance tests and the subsequent results often require active patient or advocacy involvement.
5.7 Section 5 evaluation
Please now take a few minutes to evaluate this session online.
This single page includes six short questions.
Your answers are anonymous, but the course is dependent on your feedback, which is appreciated.