Resistance

Changing treatment: second-line therapy and drug resistancewww.i-base.info/guides/changing

What is resistance?

Resistance to drugs occurs when the structure of a virus makes tiny changes that stops the treatment from working. These changes are called mutations.

You cannot develop resistance if you are not taking treatment.
You can be infected with a strain of HIV that is already resistant to some or all HIV drugs.

This is why in the UK everyone should have a resistance test before starting treatment.

You should have a resistance test if you have just been diagnosed with HIV, whether or not you plan to start treatment.

How does resistance occur?

Mutations that lead to drug resistance are generally only produced when you continue taking a treatment with a detectable viral load.

If your viral load is still above 500 copies/mL after 2-3 months, or above 50 copies/mL after 6 months, you may need to change your treatment.

Your doctor should look closely at why the results are not as good as they could be. They will want to discuss how you are managing adherence and side effects. They should also test for resistance and possibly drug levels.

Resistance can develop even at low viral load levels between 50 and 500 copies/mL.

You should have a viral load test 4 weeks after starting or changing treatment. This should then be checked every 3 months when on treatment.

Get the results when they are ready (usually after two weeks). Don't just wait until your next visit.

Some clinics let you get your blood tested 2-3 weeks before you see your doctor. Then you will have the results back for the appointment.

If your viral load has increased you should then get a second test on the same day, to confirm the results.

Often slight increases are due to errors in the test. You can also have small increases that go back down again that are called 'blips' or 'spikes'.

A re-test will check what is happening. If the combination is failing, you minimise the risk of further resistance by checking this straight away.

You will get a better response to a second treatment if you change when viral load levels are still low.

How do I avoid resistance?

If you get your viral load to under 50 copies/mL, you dramatically reduce the risk of resistance. If you are starting treatment, this is a realistic goal.

You need to use a combination that is strong enough to control the virus, and you need to take it on time, every day.

In treatment guidelines, avoiding resistance is more important than an increase in your CD4 count. Avoiding resistance will let your treatment work long-term.

What is cross-resistance?

Cross-resistance is when resistance to one drug causes resistance to other similar drugs, even if you have never taken them before.

This is particularly true of drugs in the same class.

What do the letters and numbers in resistance test results mean?

Resistance mutations are usually given a number to say where on the viral DNA that the change has taken place – like junction numbers on a motorway.

If there is a letter afterwards, this stands for the new chemical that the mutation makes. If there is a letter before this stands for the chemical that has been changed.

Missing doses, drug levels and resistance

Drug levels with good adherence

Drug doses are calculated so that average drug levels are high enough to be active against HIV without risking resistance – 24 hours a day – and low enough to minimise the risk of side effects.

Regular doses avoids low drug levels which can lead to resistance

A missed or late dose increases the risk of resistance

Missing or being late with a drug lets the drug levels fall to a level where resistance can develop. The more often you are late or miss a dose, the greater the chance this will occur.

Missed does = low drug level = rislk of resistance

The importance of different viral load levels when on treatment

If your viral load is:

Less than 50 (<50 copies/mL)
So little HIV is produced that resistance is unlikely to develop to your combination. So long as you continue taking the drugs carefully, you could use them for many years.

Between 50 and 500 (>50 and <500 copies/mL)
This is not low enough to stop resistance. At some point, as resistance becomes more extensive, the drugs will stop working and your viral load will rebound much higher.

Over 500 (>500 copies/mL)
If you continue to take treatment while your viral load is detectable (and not still falling) resistance will mean you can only use your combination for a limited time.