Boyz Doc: Dr Laura Waters on HIV drug resistance

Dear Dr Laura,

I’m living with HIV and recently my clinic told me my viral load is detectable and I have to wait for a test to see if I have any resistance to the medication. What does this mean and do I need to be worried?


Dear Paul,

People with HIV are treated with a combination of drugs (usually three) which stop the virus reproducing – the goal to get the amount of virus in the blood (also called the viral load) to ‘undetectable’ levels; this means that the test your clinic uses to measure HIV cannot detect the virus.

Getting HIV undetectable has a number of benefits:

1) The immune system returns towards normal, the CD4 count (the immune cell most affected by HIV; CD4 levels are used to monitor immune health) goes up and your risk of getting sick from HIV-related illnesses plummets

2) In the UK, if your virus is undetectable and your immune system recovers on treatment you have a NORMAL life expectancy

3) Lower risk of ‘non-HIV-related’ illness (such as heart disease) than people with untreated HIV

4) Improvement in symptoms related to HIV (such as tiredness, enlarged lymph glands)

5) UNDETECTABLE = UNTRANSMISSIBLE several studies show that where a person with HIV has an undetectable virus on treatment there have been no cases of transmission to negative partners. None.

The reason we use combinations of drugs to treat HIV is because HIV mutates easily – this means that it can alter its genetic sequence to try and overcome drugs. If a genetic change reduces the effectiveness of a drug, this is called a resistance mutation. Using more than one drug makes it much more difficult for HIV to develop resistance. Different infections vary in their ability to develop drug resistance: HIV resistance develops quite easily, chlamydia and syphilis do not so are treated with just one drug.

When you have blood tests one of the key tests is the viral load – this tells us if your treatment is working. Once you are established on treatment and have had a few undetectable results, most clinics check the viral load every 6 months. Presumably your viral load has been undetectable before and this is the first detectable result.

The main reason for having a detectable virus is that there is not enough drug in the blood to keep the virus suppressed. The most common reason for this is missing doses of drugs (also called ‘poor adherence’). Drug levels need to stay above a minimum level in order to keep the virus undetectable – if you take the drugs every day, at a similar time, you will maintain high enough levels of drug in the bloodstream but if you forget to take the medication the levels will fall. A good analogy is that the HIV drugs are a wall that the virus is trying to jump over – if the wall is lower it’s easier to jump over. If the drug levels are not high enough and the virus becomes detectable it will try to mutate and develop drug resistance. If resistance develops it may then be impossible for that drug combination to get the virus undetectable again, even with good drug levels. Using the wall analogy, resistance is like a trampoline so that even when the drug wall is higher again the virus can still get over it. Many modern drugs have enough ‘forgiveness’ to allow for the occasional missed dose and some combinations have been studied to test whether it’s OK to miss doses – an example is one of the three-in-one pills called Atripla; in one small study Atripla was taken every day during the week and then stopped for 2 doses at weekends and was still as effective as when taken every day. That’s because the drugs in Atripla leave the body quite slowly so the blood levels stay good for several hours after a missed dose. Other drugs are less ‘forgiving’. The other important factor is called the ‘genetic barrier’ – some drugs, regardless of how long they stay in the blood, are more difficult to develop resistance to.  High barrier drugs include atazanavir, darunavir and dolutegravir – it’s not impossible to get resistance, just more difficult than with other drugs.

There are other reasons for low drug levels beyond missing doses which include:

1) Not taking medication with food: some drugs needs to be taken when there is food in the stomach in order to be absorbed into the bloodstream – the drug leaflet or your clinic can tell you or the British HIV Association produce a leaflet:

2) Interactions with other drugs: some non-HIV drugs, including things you can buy over the counter, can reduce the amount of HIV drug that enters the bloodstream; examples include: the HIV drugs rilpivirine and atazanavir are affected by drugs for indigestion/heartburn, some drugs can be affected by multivitamins – speak to you clinic or check out the University of Liverpool HIV interaction site

Back to you – have a think about whether you’ve been taking your medication regularly and in the right way and also any other medications you take, including things you may have bought over the counter or online. The clinic will repeat the viral load – if it was just a low detectable level it could be an error in the test (also called a blip) in which case it will likely be undetectable again on the second test. A resistance tests looks for mutations in the virus – if you have developed resistance to one or more drugs in your combination you will be switched to an alternative. These days we can find a combination that works for almost all people with resistance and, unless you were treated in the 1980s/1990s, before we had combination therapy, its very unlikely you’d have a virus that’s difficult to treat. If you haven’t got resistance but the virus was confirmed to be detectable the clinic will talk to you about taking the medication, drug interactions etc and may offer you a different combination that suits you better or has a lower risk of resistance of you do miss doses now and then.

Dr Laura Waters is an HIV and sexual health consultant at the Mortimer Market clinic and the Boyz Doc. Dr Laura answers your questions every two weeks in Boyz. If you have a question for Dr Laura please email her at [email protected].

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