Forty years after the first cases were reported, AIDS is claiming fewer and fewer lives. Thanks to triple therapy, infected people are no longer contagious and most of them lead normal lives. However, viruses remain hidden in their organs, which prevents their complete recovery. Research conducted over the past 40 years has led to a better understanding of the complex behavior of HIV, but the strategies that will eradicate it from the body and prevent infections have yet to be found. A major challenge that the scientific community is working hard on here.
“Living with HIV is not having AIDS,” insists clinician researcher Madeleine Durand, of the CHUM. “HIV is a virus that infects humans. As soon as it is diagnosed, treatment can be started that will make the viral load undetectable. And when no more virus is detected in the person’s blood, it is not contagious, it does not transmit the infection. »
On the other hand, “if the infected person is not treated, HIV will quietly, for seven to ten years, eat away at his immune system until it becomes so weak that it will no longer be able to defend itself. organism against infections, which are called opportunistic because they do not normally affect healthy people. Before the advent of treatment, people developed opportunistic infections that characterize AIDS, and death occurred on average within six months. It was catastrophic until the beginning of 1990, ”recalls the specialist in internal medicine.
The DD Durand insists on this important distinction, because the stigmatization of people infected with HIV is still very rampant and undermines the life and health of these individuals. Many people living with HIV tell him: “My virus, there is nothing there. But what other people think of my virus is what makes me suffer. »
In Canada, HIV infections are on the rise among First Nations people and women, who face more intense stigma than men, she points out.
Although triple therapy has radically improved the life prospects of people infected with HIV, many of them will experience premature aging, especially those who have started treatment long after being infected. “People who had early screening and started treatment straight away are doing very well, they show no signs of premature aging, because the virus hasn’t had time to really weaken their immune system” , she explains.
The DD Durand leads the Canadian HIV and Aging Cohort, which includes 850 people aged 40 and over living with HIV and 250 uninfected people to compare their aging and highlight the factors that accelerate that of HIV-infected individuals. .
One of the hypotheses put forward to explain this premature aging is “chronic antigenic stimulation”. Even if HIV is undetectable in the blood of people treated, we know that there are still viruses hidden in their organs. It is believed that viral proteins from these viruses find their way into the bloodstream and cause a constant, quiet activation of the immune system, which results in sustained inflammation, which wears down the body and could accelerate cardiovascular and neurological aging. , she explains.
Andrés Finzi, specialist in retroviruses at the CHUM Research Center (CR), applies himself to measuring the fragments of viral proteins in the blood of patients at the DD Durand. The assays are then correlated with images of the coronary arteries of these same patients to determine whether individuals with more viral fragments in their blood show early signs of atherosclerosis.
The presence in the blood of bacterial particles from the gut microbiome could also contribute to ongoing inflammation that can damage the body. “In the first weeks of an HIV infection, the white blood cells posted along the intestinal barrier to prevent gut bacteria from spreading into the bloodstream have been shown to be decimated. And even after years of antiretrovirals, this contingent of white blood cells does not manage to reconstitute itself as it was before the infection”, she specifies.
Nicolas Chomont, specialist in virology at the CR du CHUM, is interested in these viral reservoirs that triple therapy fails to eliminate and which persist in the body. “Thanks to the generosity of people who had been living with HIV for a long time and who had agreed to donate their bodies to research after their death”, the researcher was able to carry out “an almost complete mapping of the reservoirs”. Thus, after the autopsy of these people, he was able to recover all their organs, from the brain to the spleen, passing through the liver, the lymph nodes, the testicles and several portions of the intestine.
“What we saw with the first two patients is not very good news, because we found the virus everywhere with more or less high concentrations: we saw a little less in the brain and the testicles by compared to organs of the immune system, such as the spleen and lymph nodes, and the gut where there were many more,” he says.
“But the good news is that the infected cells in those tissues that harbor the virus don’t just lurk in their organ, they tend to travel through the body. And if they travel, that means they have a certain vulnerability, because they are then exposed to the body’s immune defences,” he continues.
But in the majority of people on triple therapy, the immune system is unable to target these cells and eliminate them, because “it is weakened and because it has not encountered HIV for a long time – in because of the triple therapy — and that he no longer really knows what he looks like”. It must therefore be re-educated and strengthened.
Another challenge to overcome: the viruses that are hidden in these tissues are often asleep; they are said to be latent. And since cells that contain latent viruses look like any other uninfected cells, the immune system cannot see them, and therefore cannot eliminate them.
Immunotherapy against cancer is a strategy that is currently being tested by M. Chomont’s team, because it has the double advantage of waking up viruses and strengthening the response of the immune system.
Andrés Finzi is also trying to develop a strategy to destroy the infected cells that have taken refuge in the reservoirs. In order for the immune system not to recognize the cells it has infected, HIV covers them with a kind of “Harry Potter-style invisibility cloak”, he explains. Dr. Finzi has therefore designed a molecular tool that opens this cape and thus allows antibodies to recognize the infected cell and neutralize it so that it is ultimately killed.
“To patients who ask us where we are in the development of a cure for HIV, we cannot tell them anything other than: we are making progress. And it is true that we are moving forward. As much as 13 years ago, no one thought that we could eradicate HIV, today there are about ten people in the world who are considered to have no more virus in their body, whereas they’ve had it for years. It proves that it exists! says Mr. Chomont, who hopes to spot one of these “exceptional elite controllers” in Quebec who have managed to naturally get rid of all the viruses that infected them, and who no longer need treatment.
According to UNAIDS, 38.4 million people were living with HIV worldwide in 2021, but only 28.7 million had access to triple therapy. Figures that motivate scientists to continue their research.