What is Resistance?

Mutations & Resistance in HIV

Managing Resistance to HIV Therapy

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What is Resistance?

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Mutations
When living things reproduce they need to make copies of their genetic code (DNA or RNA), the "list" of genes which contain all the information needed to make another individual. When the genetic code is copied mistakes are often made which cause sudden random changes to the code. These changes are called mutations.

The genes of all life forms undergo mutations from time to time. Gene mutations usually result in a small change in a protein, often by changing just one of the hundreds of building blocks (amino acids) that make up a protein. Proteins are important. Some proteins, known as enzymes, regulate biochemical reactions while others, known as structural proteins, make up the structure of living things. Even a small change such as one amino acid can alter the structure, and therefore the function, of a protein. For an enzyme protein this could mean that an essential chemical reaction would now be unable to take place.

The frequency of mutation depends partly on how often the organism reproduces or its cells divides. Viruses, for instance, reproduce (replicate) millions of times a day, so mutations are constantly arising. Mutations that enhance an organism’s ability to reproduce will become more common in successive generations as they are "passed down" - a strain of bacterium or virus containing a favourable mutation will be selected at the expense of strains that are reproductively less "fit".

Resistance
All living things have evolved over many thousands of years to suit their environment so the natural form of a gene (the wild type) is usually the most beneficial, in terms of survival, to the organism in that environment. Most mutations will be harmful or even lethal to the organism, but a few may be beneficial.

If circumstances (such as a rise in temperature) change, a mutation might enable the organism to adapt better to the new environment. For example, during a bacterial or viral infection, the wild type virus or bacteria can normally establish a foothold and multiply rapidly because its genes instruct it to manufacture all the proteins essential for replication.

However, antibiotic or antiviral drugs can interfere with protein manufacture in bacteria and viruses by inhibiting the production of vital enzymes. In a person who takes such a drug, the wild type organisms will be killed off or prevented from multiplying further. But, because spontaneous mutations happen very frequently in bacteria and viruses, a population of infecting organisms is likely to include a number of different forms, some of which may be naturally resistant to the drug’s action.

A resistant form can quickly multiply to become the dominant type. Drug resistance can be inherited from one generation to the next. Thus a person can sometimes become infected with a strain of bacterium or virus that is already resistant to commonly used drugs.