Treatment training manual

2.13 Viral life cycle, drug resistance and adherence

Viral life cycle: copies, mistakes and mutations

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

When you are not taking ART, 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 ART, drug mutations can develop that stop a drug from working. This is called drug resistance.

  • With drug resistance, the 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 in one class are often resistant to other similar drugs in the same. For example, resistance to one NNRTI or to one interase inhibitor can stop other NNRTIs or integrase inhibitors from working. This is called cross-resistance.

Resistance, treatment and viral load

Having drug 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 HIV drugs on time in the right way every day.

Taking one or more of your drugs late – or missing doses altogether – will increase the risk of drug resistance. This is because drug levels become too low to control the virus.

To get the best levels, meds need to be taken exactly as they are prescribed. This includes special instructions on whether ART needs to be taken with food or on an empty stomach.

  • Drug interactions can also affect the levels of ARV drugs.
  • HIV drugs can interact with other HIV and OI medications (especially with treatment for TB).
  • HIV drugs 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.

Regular doses keeps drug levels high enough avoid resistance

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

Missed dose = low drug levels = risk of resistance

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.

Adherence 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 a 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.

Last updated: 1 January 2016.