HIV drug resistance mutations
3.1 Recap of previous section
The set the stage:
- We have a genetic organism – in this case a virus (HIV).
- After infecting a cell, the virus can replicates many times. HIV produces more than 100 million new virions every 1–2 days.
- But HIV has no proofreading mechanism. It makes at least one mistake (mutation) just by chance in each replication cycle.
- Someone who is not on treatment is likely to have every possible single mutation the HIV genome. We don’t have one virus but a pool or soup of thousands of slightly different types of HIV.
3.2 Introduction to section 3
Section 3 looks at how HIV mutations behave when HIV drugs are around (i.e. in the presence of drugs).
3.3 Wild-type virus and drug pressure
In someone not on treatment, mutations that develop that can affect how a drug works are made at random.
When no drug resistant mutations are present, this HIV is called ‘wild type’.
Mutations generally make HIV less fit at replicating. Wild type HIV is therefore stronger and fitter that drug resistant HIV.
When not on treatment, drug resistant HIV has no advantage over the wild type. It is less fit and so wild type continues to be dominant. The muation may still be in the pool of viruses but it will stay a minority.
- The main strain will be the fittest virus (ie wild type when not on treatment).
- A mutation that stops a drug working is called ‘a mutation associated with drug resistance’ or, more commonly, ‘a drug resistant mutation’.
- As long as you are not taking the drug associated with this resistance, this mutation will have no relative advantage over wild type virus.
Now think about how the pool of viruses will change if you start taking this drug.
- The drug will be able to kill most of the viruses in the pool. However, it will not be active against the virus that is resistant to the drug.
- The drug resistant virus will continue to replicate. This resistant virus now has an advantage over the other viruses. It is relatively more fit.
- Slowly, the drug resistant HIV will become dominant in the pool.
- In the presence of the drug, further mutations can develop and make the resistance even stronger.
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