HIV reproduces very quickly, making billions of new viruses every day. Because it almost always makes errors while copying itself, each new generation of viruses differs slightly from the one before.

The naturally occurring strains of HIV, which are susceptible to antiretroviral drugs, are known as "wild-type". Researchers estimate that every possible error in the wild-type structure of HIV occurs once every day if virus production is not being suppressed. Some of these errors produce viruses which are defective and so cannot reproduce themselves well. Over time these 'less fit' viruses will die off. However, certain changes to the structure of the virus can improve its ability to reproduce even if high levels of anti-HIV drugs are present. These HIV variants are said to be drug-resistant.