HIV is resilient, and unfortunately that’s not the best news for patients. Ask any researcher trying to stop the virus dead in its tracks for the past 35 years, and they’ll tell you. HIV is a moving target that’s cunning and forever changing. It is to the body what dust is to a home: difficult to eliminate.
HIV’s strength lies in its very high rate of mutation. When the virus infects a cell, it uses it to make many copies of itself. But this cloning process is flawed and genetic mutations are common. While most mutations generate non-functional viruses, some produce a new version of the virus. And the new variant can be resistant to a drug that killed the original virus.
Since HIV can make a huge number of copies of itself in a short time – a single virus can have 10,000 descendants in only 24 hours – people with the disease will have many variants of the virus all living inside them at the same time. These variants do not respond to the same medications.
“As a result of these replication errors, the same patient can have 15 to 20 genetic variants of the disease,” says Dr. Michel Roger, Microbiologist and Infectious Disease Specialist at the Centre hospitalier de l’Université de Montréal. “This is why we use a cocktail of drugs to treat it. Triple therapy, for instance, attacks HIV on several fronts simultaneously.”
Some patients can also experience a sudden increase in their viral load after having had the disease under control. This happens when a treatment-resistant variant has arrived on the scene and taken over.
This is where pharmacogenetics comes in. A genetic analysis is conducted on blood from a patient in order to identify all the different variants present. “Four of the fifteen or so HIV genes are sequenced, and from there, we predict the resistance using the genetic variations identified,” explains Dr. Roger. The traditional testing methods were not very efficient. “We could find all the variants that exceeded 20 percent, but if a virus represented only 5 percent of the viral load, it went undetected. The patient’s drug therapy could not be adjusted accordingly,” says Dr. Roger. “But with the latest generation sequencing methods, we can bring that number down to 1 percent, making it much harder for new viral strains to ‘slip under the radar.’”
Richard Harrigan at the University of British Columbia is conducting this research. The tests are being carried out here in Montréal, among other places.
“Our tests deal with the tropism of the virus,” says Dr. Roger. “We know that some viral strains – not all – use a certain receptor at the surface of cells to enter them. There are drugs that can attach to these receptors in a way that blocks HIV. Unfortunately these drugs come with quite a few side effects. With specific genetic testing, we can make sure we are dealing with a strain that uses the receptor in this way, then simply not administer that particular drug for nothing.”
HIV is resistant, but one day resistance will be futile.