Viral life cycle: copies, mistakes and mutations

Everyone who is HIV-positive and not on treatment produces several billion new copies of HIV every day. In making this vast number of copies of itself, the virus also makes lots of very small mistakes. These are called mutations.

When you are not taking ARVs, the virus probably produces every single possible mutation. But there is no reason for any particular mutations to develop because:

• Mutations are usually weaker than the original (wild-type) HIV.
• Wild-type HIV and mutations compete to reproduce and the stronger virus wins!

When you are taking ARVs, mutations that are unaffected by HIV drugs can appear. This is called resistance.

• In this situation, resistant virus is more effective at reproducing than non-resistant virus.
• Resistant mutations that continue to reproduce eventually become the major type of HIV in your body.
• Mutations resistant to a drug are often resistant to other similar drugs. This is called cross-resistance.

Resistance, treatment and viral load

Having resistant mutations means HIV drugs do not work as well. Sometimes they stop working completely.

• The higher your viral load when you are on treatment, the more likely that you will develop resistance.
• This is why treatment guidelines emphasise that it is important to get your viral load as low as possible, as quickly as possible, and ideally below 50 copies/mL.

Resistance and adherence are closely related

The mutations that occur when you have low concentrations of your drugs in your body can stop the drugs working. Adherence is therefore critical.

Adherence means taking your drugs on time in the right way every day.

If you miss, or are late, taking one or all of your drugs, you increase the chance of developing resistance. This is because your body no longer contain the lowest levels of drugs needed to control the virus.

In order to make sure that you get the correct level of each drug, it is important to follow any special instructions on whether treatment needs to be taken with food or on an empty stomach.

• Drug interactions can also affect the levels of ARV drugs.
• ARVs can interact with other HIV and OI medications (especially with treatment for TB).
• ARVs can also interact with some recreational drugs, and complementary and herbal drugs.
• Always tell your doctor and pharmacist about any other medications or treatments that you are taking.

Drug levels and resistance

Taking drugs at the exact same time makes sure that you keep the drug in the body above the lowest level needed to keep HIV under control.

Each time you take a drug, the level of the drug stays above the lowest level needed to keep HIV under control.

If you are late with a dose, or miss one altogether, the drug falls below the lowest level needed to keep HIV under control. Resistance can then develop.

Occasionally missing or being late with a dose (say once a month) may not make very much difference.

If you are missing or being late with a dose even once a week though, this will increase the time the virus has to develop resistance, and will increase the chance you will develop resistance over time.

Adherence is not about doing things on time just because your doctor says so. It is about keeping minimum levels of each drug in your body 100% of the time that you are on treatment.

Further reading

i-Base have developed a more detailed online training course of drug resistance.

This online course is an learning resource for HIV advocates who want to learn about HIV and resistance.

Each module should take 30–60 minutes. It was published in February 2011.