Important monitoring tests – viral load & resistance tests

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• Viral load tests
• Resistance tests
• Individual drug sensitivity cut-off values

More about tests:

• Therapeutic drug monitoring (TDM)
• Inhibitory quotient and viral tropism test
• Getting the tests in the UK

Viral load tests

Viral load tests are the most sensitive test to check whether a treatment is still working well. Your clinic should use tests sensitive to 40 or 50 copies/mL.

Viral load should be checked 2-4 weeks after any treatment change.

Once viral load is undetectable you should be monitored with a viral load test at every 3 - 4 months.

Resistance tests

Resistance tests can show which drugs you have developed resistance to and which drugs are unlikely to work.

UK treatment guidelines recommend that everyone changing treatment should have a resistance test.

You generally need to have a viral load over 500-1000 copies/mL to produce a reliable result. You also need to have blood taken while you are still using your failing combination.

Types of resistance tests

There are two types of these blood tests.

1). A genotypic resistance test looks at the structure of your virus and how it has changed from normal 'wild type' virus. Different changes are associated with resistance to different drugs.

2). A phenotype resistance tests see whether HIV drugs still work to control your type of HIV.

Note: Resistance tests can only detect resistance to drugs that you are currently taking or have recently been taking. A ‘virtual phenotype’ test compares results from your genotype test to a large database of phenotype results to predict your phenotype.

Genotype tests (mutation changes)

A genotypic resistance test looks at the structure of your virus and how it has changed from normal 'wild type' virus. Different changes are associated with resistance to different drugs.

By checking the changes in your virus to these known mutations you get a good idea of which drugs are unlikely to work.

Although this test does not register very low levels of resistance, it can still be vital as a guide to choosing drugs for your next combination.

Results should take about a week.

Although genotype tests cannot predict which drugs WILL work, they can predict which drugs WILL NOT and with multi-drug resistance, this information is just as important.

Phenotype tests (‘fold’ changes)

A phenotypic resistance test adds each drug to your HIV in a test tube. It shows how sensitive or resistant you are and how well each drug is working. Results are given in terms of how much more resistant your virus is compared to a sensitive virus.

For example, 10-fold resistance to a drug means you need 10 times as much drug to get the same anti-HIV effect.

Interpreting phenotype tests is complicated. Sometimes it is not clear at what level individual drugs remain active, and each drug can be different.

Phenotype tests are recommended in the UK guidelines when genotype results alone do not provide a clear result.

Phenotype resistance tests are 3-4 times more expensive than genotype tests. They take longer to get results - usually 2­–4 weeks - because the tests cannot be run in your own clinic and it takes time for the virus to grow.

Virtual phenotype tests

The ‘Virtual Phenotype’ test, available in some clinics, uses results from a genotype test and compares this to a large database of matched phenotype results.

How to interpret resistance tests

Resistance tests are complicated to interpret, but luckily test results also come with a summary that lists each drug as sensitive, intermediate or resistant.

Genotype = letters and numbers

Genotypic resistance tests give results as a list of mutations.

These usually follow the format of a letter followed by a number followed by a letter - ie K103N which results in complete resistance to efavirenz and nevirapine.

The first letter stands for the chemical that is normally expected at that position in the virus. ie K stands for lysine.

The number says where on the HIV DNA that the change has taken place - like junction numbers on a motorway. In this example 103 refers to the 103rd amino acid in the reverse transcriptase section of the HIV genome.

The final letter stands for the new chemical that the mutation makes, ie N stands for asparagine.

Some mutations like K103N are easy to interpret but most others are more complicated. This is because they may only have a small effect, or because they are more rare, or because they commonly occur whether or not you are on treatment.

The Stanford Resistance Database includes interpretation charts for every genotypic mutation.
http://hivdb.stanford.edu

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This is the web edition of the i-Base guide Changing treatment: second-line therapy and drug resistance. This guide is available in UK clinics. You can order free printed copies or download a PDF version (396 Kb). There are also several translations.

Information on this website is provided as a guide only. All treatment decisions should be taken in consultation with your doctor or other healthcare professional. Authors and credits. Full section index. Glossary.