[LUM#5] AIDS: a molecule for a better life
For now, there is no cure. But is it possible to live a normal life despite HIV? In Montpellier, the discovery of a new molecule is giving rise to hope.
1983: A team at the Pasteur Institute isolates the "human immunodeficiency virus," or HIV, for the first time in a laboratory: a virus that attacks the immune system, gradually destroying it. This discovery marks the beginning of a dark decade. Research struggles to combat the complex mechanisms of a disease that is synonymous with a death sentence.
Triple therapy and side effects
A decisive step was taken in 1996, when a combination of three treatments was launched on the market for the first time: the famous triple therapies. "Their arrival was a boon for patients who had failed other treatments, as they minimized the virus's resistance to the monotherapies that had been administered until then," explains Jamal Tazi, a researcher at the Institute of Molecular Genetics in Montpellier. This major advance is nonetheless limited by a multitude of side effects: headaches, diarrhea, vomiting, accelerated tissue aging, inflammation, fever, etc.
In addition to the physical consequences, there is social exclusion and the obligation to undergo treatment every day for the rest of one's life... But the key point is this: for the first time, HIV has gone from being a fatal disease to a chronic illness. A disease which, if detected and treated in time, no longer threatens the lives of patients.
Relieving patients
Twenty years and millions of victims later, a cure for the disease is still elusive. The only proven case of a cure is that of the now famous "Berlin patient" in 2007 . But the story of this American, Timothy Brown, is an exception that proves the rule. "This is a patient who received a transplant using cells carrying a mutation in a gene that happens to be a receptor for the virus, CCR5. But this is an exceptional, lucky and somewhat mythical case that has never been replicated since," says the geneticist.
While a miracle cure is not on the horizon, research is now focusing on new approaches. "The researchers' goal is now very clear: to find drugs with a new mode of action to replace triple therapy, which has shown its limitations," summarizes Jamal Tazi.
One of the most promising avenues is that of a "functional cure. " "It is no longer a question of eradicating the virus from the body, which seems illusory, but of suppressing its expression. What we hope to achieve in the long term is to free patients from the obligation of taking medication every day," explains Jamal Tazi. The quest for this functional cure has become the be-all and end-all of HIV research and is at the heart of the work carried out by the IGMM researcher. And this molecule discoverer may have struck gold with ABX464 ( First evidence of antiviral activity and safety of ABX464 in treatment-naïve HIV patients, in Journal of Virus Eradication, 2016).
Limiting the "rebound effect"
This molecule, whose role is to prevent the production of viral RNA responsible for virus replication, has a specific feature that could make all the difference: its ability to maintain viral load at a very low level for up to several weeks after treatment has stopped. ABX464 could thus counteract the so-called "rebound effect" mechanism, in other words, the rise in viral load when medication is stopped, which is the main obstacle to a functional cure.
"The treatment is still being tested, but we have so far found that ABX464 sustainably reduces viral load in patients, without any side effects. This is very encouraging. Our work has also been very well received by the scientific community." A less burdensome treatment that needs to be taken less often is the prospect opened up by the discovery of this molecule, developed in Montpellier in a joint laboratory bringing together teams from the IGMM and the biotechnology company Abivax.
How often will patients need to take this treatment: once a week, once a month, every six months? This is what the phase 2 (of 3) clinical trial currently underway, with results expected in April 2017, will determine. Although the drug is still a long way from being marketed, which is not expected to happen for several years, the molecule discovered by the IGMM raises hopes that were once considered illusory: living a normal life with AIDS.
In Montpellier, on the trail of HIV
Where did the AIDS virus first appear? How did the disease migrate from monkeys to humans? Researchers at the international laboratory "Translational Research on HIV and Infectious Diseases"finally have the answers to these puzzles. Tracing the virus back, they identified for the first time in 2014 the geographical epicenter and point of origin of HIV-1, the main variant of HIV. This gigantic treasure hunt was solved by comparing hundreds of HIV samples and socio-economic data. The researchers demonstrated that it was in southeastern Cameroon, around 1920, that the retrovirus was first transmitted from its original host—monkeys—to humans. The researchers were then able to trace the dynamics of the disease's spread, showing how it spread from its birthplace in the rainforest to Kinshasa, the starting point of an epidemic facilitated by the development of river and rail transport (documentary AIDS, on the African trail).
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