How HIV develops resistance to key drugs discovered

The mechanism behind how HIV can develop resistance to a widely prescribed group of drugs has been uncovered by new research, with the findings opening the door to the development of more effective treatments.
Today a number of drugs are available which help to control HIV infection, including a group called integrase strand transfer inhibitors. There are four drugs within this family of medication: raltegravir, elvitegravir, dolutegravir, bictegravir. They all work by binding with one of HIV's key enzymes, called integrase, to stop it from inserting the virus genetic information into DNA of human cells. While initially highly effective, over time HIV can develop resistance to these drugs.
The study discovered the mechanism HIV uses to develop resistance to this group of drugs. Although the drugs are normally very effective at binding and blocking integrase, over time, the virus can weaken this bond and thus enable its key enzyme to work again.
The researchers uncovered this by exploring the structure of integrase from a virus that is highly similar to the ancestor of HIV, using cryo- electron microscopy. This technique uses a powerful microscope which fires electron at a frozen sample of the drug enzyme complex. By recording how the electrons interact with the samples, the researchers created detailed images, at a nearly atom by atom level.
The unusual property of these drugs is that they interact with metal ions, which normally allows them to make very strong bonds to the viral enzyme's active site. It was founded that HIV can subtly alter the chemical environment of the metals, and as if using a remote control, reduce the strength of drug binding.
 Although the good news is the precise structure of the viral enzyme's active site, right where the drug binds has been visualised. These blueprints will inform the design of more effective integrase inhibitors that could improve the life of millions of people with HIV.