[LUM#5] AIDS: a molecule for a better life
For the moment, there's no cure. But can you live a normal life despite HIV? In Montpellier, the discovery of a new molecule has raised hopes.
1983: a team at the Institut Pasteur isolates the "human immunodeficiency virus", or HIV, for the first time in the laboratory: a virus that attacks the immune system, gradually destroying it. This discovery marked the start of a dark decade. Research was struggling to combat the complex mechanisms of a disease synonymous with a death sentence.
Therapies and side effects
A decisive step was taken in 1996, when a combination of three treatments was marketed for the first time: the famous tritherapies. " Their arrival was a stroke of luck for patients experiencing treatment failure, as they helped minimize the virus' resistance to treatments previously administered as monotherapy," explains Jamal Tazi, a researcher at Montpellier's Institute of Molecular Genetics. This major advance is nevertheless limited by a multitude of side effects: headaches, diarrhoea, vomiting, accelerated ageing of tissues, inflammation, fever attacks...
The physical consequences are compounded by social exclusion and the need to undergo treatment every day for the rest of one's life... But the main point is this: for the first time, HIV has been transformed from a fatal disease into a chronic illness. A disease which, if detected and treated in time, no longer threatens patients' lives.
Relieving patients
20 years and millions of victims later, the disease has yet to be cured. The only case of a proven cure was that of the now famous "Berlin patient" in 2007 . But the story of this American, Timothy Brown, is the exception that proves the rule. "He 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 was an exceptional, fortunate and somewhat mythical case, which has never been reproduced since," says the geneticist.
While a miracle treatment may not be on the horizon, research is now focusing on new approaches. " Researchers' wishes are very clear today: to find drugs with a new mode of action to replace tritherapies, which have shown their limitations," summarizes Jamal Tazi.
One of the most promising avenues is that of a "functional cure". "It's no longer a question of eradicating the virus inside the body, which seems illusory, but of numbing its expression. Ultimately, we hope to free patients from the need to take daily medication," explains Jamal Tazi. Having become the alpha and omega of HIV research, the quest for this functional cure is precisely at the heart of the work carried out by the IGMM researcher. And this molecule discoverer may have put his finger on a nugget: ABX464 ( First evidence of the antiviral activity and safety of ABX464 in HIV treatment-naive patients, in Journal of Viral Eradication, 2016).
Limiting the "rebound effect
This molecule, whose role is to prevent the production of the viral RNAs responsible for virus replication, has a specificity that could make all the difference: its ability to maintain viral load at a very low level, for up to several weeks after treatment discontinuation. ABX464 could thus counter the so-called "rebound effect" mechanism, i.e. the rise in viral load when medication is stopped, the main stumbling block on the road to a functional cure.
"The treatment is still being tested, but so far we've seen that ABX464 permanently reduces viral load in patients, with no side effects. This is very encouraging. Our work has been very well received by the scientific community. A less burdensome treatment that needs to be taken less often - this is the prospect opened up by the discovery of this molecule, developed in Montpellier within a joint laboratory involving the IGMM teams and the biotechnology company Abivax.
How often should patients take this treatment: once a week, once a month, every six months? This is the question to be answered by the phase 2 (of 3) clinical trial currently underway, the results of which are expected in April 2017. Although we are still a long way from a market launch, which is not expected for several years yet, the molecule discovered by IGMM does raise a hope that was once considered illusory: living normally 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 " Translational Research on HIV and Infectious Diseases " laboratory finally have the answers to these enigmas. Tracing the virus's trail, in 2014 they identified for the first time the geographic epicenter and point of origin of HIV-1, the main HIV variant. This gigantic treasure hunt was solved by comparing hundreds of HIV samples with socio-economic data. The researchers thus demonstrated that it was in south-east Cameroon, around 1920, that the retrovirus was first transmitted from its original host - the monkey - to human beings. The researchers were then able to retrace the dynamics of the disease's spread, showing how it spread from its cradle in the rainforest to Kinshasa, the starting point of an epidemic facilitated by the development of river and rail transport (" Sida, sur la piste africaine" documentary).
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